Journal: Ann Intern Med

Sorted by: date / impact
Abstract

Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension : A Systematic Review and Individual Participant-based Meta-analysis.

Juraschek SP, Hu JR, Cluett JL, Ishak A, ... Wright JT, Mukamal KJ
Background
Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).
Purpose
To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults. (PROSPERO: CRD42020153753).
Data sources
MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.
Study selection
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.
Data extraction
Two investigators independently abstracted articles and rated risk of bias.
Data synthesis
Five trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH ( for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.
Limitations
Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.
Conclusion
Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.
Primary funding source
National Heart, Lung, and Blood Institute, National Institutes of Health.



Ann Intern Med: 09 Sep 2020; epub ahead of print
Juraschek SP, Hu JR, Cluett JL, Ishak A, ... Wright JT, Mukamal KJ
Ann Intern Med: 09 Sep 2020; epub ahead of print | PMID: 32909814
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Abstract

Age- and Weight-Adapted Dose of Prasugrel Versus Standard Dose of Ticagrelor in Patients With Acute Coronary Syndromes : Results From a Randomized Trial.

Menichelli M, Neumann FJ, Ndrepepa G, Mayer K, ... Schüpke S, Kastrati A
Background
The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown.
Objective
To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800).
Design
Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial.
Setting
23 centers in Germany and Italy.
Patients
3997 patients with ACS planned for invasive management.
Intervention
Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group).
Measurements
The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months.
Results
In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88];for interaction > 0.2). In the elderly or low-weight group, Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of patients assigned to receive prasugrel and 10.6% of those assigned to receive ticagrelor (HR, 0.72 [0.46 to 1.12]), and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (HR, 0.98 [CI, 0.65 to 1.47];for interaction > 0.2).
Limitation
The study is a subgroup analysis.
Conclusion
In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding.
Primary funding source
German Center for Cardiovascular Research and Deutsches Herzzentrum München.



Ann Intern Med: 14 Sep 2020; 173:436-444
Menichelli M, Neumann FJ, Ndrepepa G, Mayer K, ... Schüpke S, Kastrati A
Ann Intern Med: 14 Sep 2020; 173:436-444 | PMID: 32687741
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Abstract

Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial.

Charles P, Perrodeau É, Samson M, Bonnotte B, ... Mouthon L, Guillevin L
Background
Biannual rituximab infusions over 18 months effectively maintain remission after a \"standard\" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
Objective
To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen.
Design
Randomized controlled trial. (ClinicalTrials.gov: NCT02433522).
Setting
39 clinical centers in France.
Patients
68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy.
Intervention
Rituximab or placebo infusion every 6 months for 18 months (4 infusions).
Measurements
The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0.
Results
From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) ( = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) ( = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group.
Limitation
Potential selection bias based on previous rituximab response and tolerance.
Conclusion
Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy.
Primary funding source
French Ministry of Health and Hoffmann-La Roche.



Ann Intern Med: 03 Aug 2020; 173:179-187
Charles P, Perrodeau É, Samson M, Bonnotte B, ... Mouthon L, Guillevin L
Ann Intern Med: 03 Aug 2020; 173:179-187 | PMID: 32479166
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Abstract

Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings.

Bastos ML, Campbell JR, Oxlade O, Adjobimey M, ... Schwartzman K, Menzies D
Background
Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen.
Objective
To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid.
Design
Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209).
Setting
High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea).
Participants
Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection.
Measurements
Health system costs per participant.
Results
A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population.
Limitation
Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines.
Conclusion
A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection.
Primary funding source
Canadian Institutes of Health Research.



Ann Intern Med: 03 Aug 2020; 173:169-178
Bastos ML, Campbell JR, Oxlade O, Adjobimey M, ... Schwartzman K, Menzies D
Ann Intern Med: 03 Aug 2020; 173:169-178 | PMID: 32539440
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Abstract

Racism and Health in the United States: A Policy Statement From the American College of Physicians.

Serchen J, Doherty R, Atiq O, Hilden D

Racial minorities in the United States have reported experiencing widespread racism throughout all aspects of life, from housing to education to employment. Existing research has examined the role of racism, discrimination, and violence in one\'s interaction with the health care system and their association with poorer mental and physical health. Systemic racism that underlies the fabric of society often manifests itself in prominent institutions, such as law enforcement agencies, regardless of individual intent. Overt and covert racist laws and policies, personal implicit biases, and other factors result in Black individuals and other people of color being the subject of law enforcement violence and criminal justice system interactions at disproportionately high rates. The demonstrated association between discriminatory law enforcement practices and violence and personal and community health necessitates treating these issues as public health issues worthy of a public policy intervention. Addressing some of the sources of institutional racism and harm through transparency and accountability measures is the first of many steps required to begin correcting historical racial injustices.



Ann Intern Med: 05 Oct 2020; 173:556-557
Serchen J, Doherty R, Atiq O, Hilden D
Ann Intern Med: 05 Oct 2020; 173:556-557 | PMID: 32559145
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Impact:
Abstract

Extreme Risk Protection Orders in Washington : A Statewide Descriptive Study.

Rowhani-Rahbar A, Bellenger MA, Gibb L, Chesnut H, ... Haviland MJ, Rivara FP
Background
In the United States, 74% of homicides and 51% of suicides involve firearms. Using extreme risk protection order (ERPO) laws, petitioners can request restricting firearm access for individuals (known as \"respondents\") who pose a risk to themselves or others.
Objective
To characterize respondents and circumstances of ERPOs.
Design
Descriptive study.
Setting
State of Washington.
Participants
All ERPO respondents during 8 December 2016 to 10 May 2019.
Measurements
Reason for filing the ERPO; characteristics of respondents; respondent\'s reported history of domestic violence perpetration, mental illness, substance misuse, and suicide ideation or attempt; number and type of firearms removed; and ERPO petition outcome (granted or not granted).
Results
The ERPOs were filed for concerns about harm to self ( = 67), harm to others ( = 86), or harm to both self and others ( = 84). Of all ERPOs, 87% were filed by law enforcement and 81% were granted. At least 1 firearm was removed from 64% of respondents, with a total of 641 firearms removed. The petitioner reported prior domestic violence perpetration by the respondent in 24% of cases, and a prior diagnosis of a mental health condition and substance misuse for the respondent in 40% and 47% of cases, respectively. Of all respondents, 62% had a history of suicidal ideation or attempt according to the petitioner. As part of the ERPO process, the court ordered mental health evaluation in 30% of cases.
Limitation
Filing of the forms was inconsistent.
Conclusion
Laws regarding ERPOs are a potential tool to help protect patients or family members from harming themselves or others by restricting firearm possession and purchase. Further studies are needed to determine the long-term effects of these laws and identify approaches to increase their use.
Primary funding source
State of Washington.



Ann Intern Med: 31 Aug 2020; 173:342-349
Rowhani-Rahbar A, Bellenger MA, Gibb L, Chesnut H, ... Haviland MJ, Rivara FP
Ann Intern Med: 31 Aug 2020; 173:342-349 | PMID: 32598226
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Abstract

Risk for Subdeltoid Bursitis After Influenza Vaccination: A Population-Based Cohort Study.

Hesse EM, Navarro RA, Daley MF, Getahun D, ... Zheng C, Duffy J
Background
Subdeltoid bursitis has been reported as an adverse event after intramuscular vaccination in the deltoid muscle. Most published case reports involved influenza vaccine.
Objective
To estimate the risk for subdeltoid bursitis after influenza vaccination.
Design
Retrospective cohort study.
Setting
The Vaccine Safety Datalink, which contains health encounter data for 10.2 million members of 7 U.S. health care organizations.
Patients
Persons who received an inactivated influenza vaccine during the 2016-2017 influenza season.
Measurements
Potential incident cases were identified by searching administrative data for persons with a shoulder bursitis diagnostic code within 180 days after receiving an injectable influenza vaccine in the same arm. The date of reported bursitis symptom onset was abstracted from the medical record. A self-controlled risk interval analysis was used to calculate the incidence rate ratio of bursitis in a risk interval of 0 to 2 days after vaccination versus a control interval of 30 to 60 days, which represents the background rate. The attributable risk was also estimated.
Results
The cohort included 2 943 493 vaccinated persons. Sixteen cases of symptom onset in the risk interval and 51 cases of symptom onset in the control interval were identified. The median age of persons in the risk interval was 57.5 years (range, 24 to 98 years), and 69% were women. The incidence rate ratio was 3.24 (95% CI, 1.85 to 5.68). The attributable risk was 7.78 (CI, 2.19 to 13.38) additional cases of bursitis per 1 million persons vaccinated.
Limitation
The results may not be generalizable to vaccinations done in other types of health care settings.
Conclusion
Although an increased risk for bursitis after vaccination was present, the absolute risk was small.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 17 Aug 2020; 173:253-261
Hesse EM, Navarro RA, Daley MF, Getahun D, ... Zheng C, Duffy J
Ann Intern Med: 17 Aug 2020; 173:253-261 | PMID: 32568572
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Abstract

Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings : A Living Rapid Review.

Chou R, Dana T, Jungbauer R, Weeks C, McDonagh MS
Background
Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary.
Purpose
To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks.
Data sources
Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists.
Study selection
Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods.
Data extraction
One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification.
Data synthesis
39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common.
Limitations
There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods.
Conclusion
Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain.
Primary funding source
Agency for Healthcare Research and Quality.



Ann Intern Med: 05 Oct 2020; 173:542-555
Chou R, Dana T, Jungbauer R, Weeks C, McDonagh MS
Ann Intern Med: 05 Oct 2020; 173:542-555 | PMID: 32579379
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Abstract

Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy : A Cohort Study.

Del Amo J, Polo R, Moreno S, Díaz A, ... Jarrín I, Hernán MA
Background
The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations.
Objective
To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART.
Design
Cohort study.
Setting
HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020.
Participants
77 590 HIV-positive persons receiving ART.
Measurements
Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models.
Results
Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died.
Limitation
Residual confounding by comorbid conditions cannot be completely excluded.
Conclusion
HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV.
Primary funding source
Instituto de Salud Carlos III and National Institutes of Health.



Ann Intern Med: 05 Oct 2020; 173:536-541
Del Amo J, Polo R, Moreno S, Díaz A, ... Jarrín I, Hernán MA
Ann Intern Med: 05 Oct 2020; 173:536-541 | PMID: 32589451
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Abstract

Developing Primary Care-Based Recommendations for Social Determinants of Health: Methods of the U.S. Preventive Services Task Force.

Davidson KW, Kemper AR, Doubeni CA, Tseng CW, ... Ngo-Metzger Q, Borsky A

The purpose of the U.S. Preventive Services Task Force (USPSTF) is to provide evidence-based recommendations on primary care screening, behavioral counseling, and preventive medications. A person\'s health is strongly influenced by social determinants of health, such as economic and social conditions; therefore, preventive recommendations that address these determinants would be ideal. However, differing social determinants have been proposed by a wide range of agencies and organizations, little prevention evidence is available, and responsible parties are in competition, all of which make the creation of evidence-based prevention recommendations for social determinants of health challenging. This article highlights social determinants already included in USPSTF recommendations and proposes a process by which others may be considered for primary care preventive recommendations. In many ways, incorporating social determinants of health into evidence-based recommendations is an evolving area. By reviewing the evidence on the effects of screening and interventions on social determinants relevant to primary care, the USPSTF will continue to provide recommendations on clinical preventive services to improve the health of all Americans.



Ann Intern Med: 14 Sep 2020; 173:461-467
Davidson KW, Kemper AR, Doubeni CA, Tseng CW, ... Ngo-Metzger Q, Borsky A
Ann Intern Med: 14 Sep 2020; 173:461-467 | PMID: 32658576
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Abstract

Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

Tsapas A, Avgerinos I, Karagiannis T, Malandris K, ... Matthews DR, Bekiari E
Background
Several pharmacologic options for type 2 diabetes are available.
Purpose
To compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes.
Data sources
Several databases from inception through 18 December 2019 and ClinicalTrials.gov on 10 April 2020.
Study selection
English-language randomized trials that had at least 24 weeks of intervention and assessed the effects of glucose-lowering drugs on mortality, glycemic, and vascular outcomes.
Data extraction
Pairs of reviewers extracted data and appraised risk of bias.
Data synthesis
453 trials assessing 21 antidiabetic interventions from 9 drug classes were included. Interventions included monotherapies (134 trials), add-on to metformin-based therapies (296 trials), and monotherapies versus add-on to metformin therapies (23 trials). There were no differences between treatments in drug-naive patients at low cardiovascular risk. Insulin regimens and specific glucagon-like peptide-1 receptor agonists (GLP-1 RAs) added to metformin-based background therapy produced the greatest reductions in hemoglobin A level. In patients at low cardiovascular risk receiving metformin-based background treatment (298 trials), there were no clinically meaningful differences between treatments for mortality and vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background treatment (21 trials), oral semaglutide, empagliflozin, liraglutide, extended-release exenatide, and dapagliflozin reduced all-cause mortality. Oral semaglutide, empagliflozin, and liraglutide also reduced cardiovascular death. Odds of stroke were lower with subcutaneous semaglutide and dulaglutide. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduced heart failure hospitalization and end-stage renal disease. Subcutaneous semaglutide and canagliflozin increased diabetic retinopathy and amputation, respectively.
Limitation
Inconsistent definitions of cardiovascular risk and low-level confidence in some estimates for patients at low cardiovascular risk.
Conclusion
In diabetic patients at low cardiovascular risk, no treatment differs from placebo for vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and SGLT-2 inhibitors have a favorable effect on certain cardiovascular outcomes.
Primary funding source
European Foundation for the Study of Diabetes, supported by an unrestricted educational grant from AstraZeneca. (PROSPERO: CRD42019122043).



Ann Intern Med: 17 Aug 2020; 173:278-286
Tsapas A, Avgerinos I, Karagiannis T, Malandris K, ... Matthews DR, Bekiari E
Ann Intern Med: 17 Aug 2020; 173:278-286 | PMID: 32598218
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Impact:
Abstract

Analysis of Response Data for Assessing Treatment Effects in Comparative Clinical Studies.

Huang B, Tian L, McCaw ZR, Luo X, ... Kim DH, Wei LJ

In comparative studies, treatment effect is often assessed using a binary outcome that indicates response to the therapy. Commonly used summary measures for response include the cumulative and current response rates at a specific time point. The current response rate is sometimes called the probability of being in response (PBIR), which regards a patient as a responder only if they have achieved and remain in response at present. The methods used in practice for estimating these rates, however, may not be appropriate. Moreover, whereas an effective treatment is expected to achieve a rapid and sustained response, the response at a fixed time point does not provide information about the duration of response (DOR). As an alternative, a curve constructed from the current response rates over the entire study period may be considered, which can be used for visualizing how rapidly patients responded to therapy and how long responses were sustained. The area under the PBIR curve is the mean DOR. This connection between response and DOR makes this curve attractive for assessing the treatment effect. In contrast to the conventional method for analyzing the DOR data, which uses responders only, the above procedure includes all patients in the study. Although discussed extensively in the statistical literature, estimation of the current response rate curve has garnered little attention in the medical literature. This article illustrates how to construct and analyze such a curve using data from a recent study for treating renal cell carcinoma. Clinical trialists are encouraged to consider this robust and clinically interpretable procedure as an additional tool for evaluating treatment effects in clinical studies.



Ann Intern Med: 31 Aug 2020; 173:368-374
Huang B, Tian L, McCaw ZR, Luo X, ... Kim DH, Wei LJ
Ann Intern Med: 31 Aug 2020; 173:368-374 | PMID: 32628533
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Impact:
Abstract

Association Between Oral Corticosteroid Bursts and Severe Adverse Events : A Nationwide Population-Based Cohort Study.

Yao TC, Huang YW, Chang SM, Tsai SY, Wu AC, Tsai HJ
Background
Long-term use of oral corticosteroids has known adverse effects, but the risk from brief oral steroid bursts (≤14 days) is largely unknown.
Objective
To examine the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure.
Design
Self-controlled case series.
Setting
Entire National Health Insurance Research Database of medical claims records in Taiwan.
Participants
Adults aged 20 to 64 years with continuous enrollment in the National Health Insurance program from 1 January 2013 to 31 December 2015.
Measurements
Incidence rates of severe adverse events in steroid burst users and non-steroid users, as well as incidence rate ratios (IRRs) for severe adverse events within 5 to 30 and 31 to 90 days after initiation of steroid therapy.
Results
Of 15 859 129 adult participants, 2 623 327 who received a single steroid burst were included. The most common indications were skin disorders and respiratory tract infections. The incidence rates per 1000 person-years in steroid bursts were 27.1 (95% CI, 26.7 to 27.5) for GI bleeding, 1.5 (CI, 1.4 to 1.6) for sepsis, and 1.3 (CI, 1.2 to 1.4) for heart failure. Rates of GI bleeding (IRR, 1.80 [CI, 1.75 to 1.84]), sepsis (IRR, 1.99 [CI, 1.70 to 2.32]), and heart failure (IRR, 2.37 [CI, 2.13 to 2.63]) significantly increased within 5 to 30 days after steroid therapy initiation and attenuated during the subsequent 31 to 90 days.
Limitation
Persons younger than 20 years or older than 64 years were not included.
Conclusion
Oral corticosteroid bursts are frequently prescribed in the general adult population in Taiwan. The highest rates of GI bleeding, sepsis, and heart failure occurred within the first month after initiation of steroid therapy.
Primary funding source
National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.



Ann Intern Med: 31 Aug 2020; 173:325-330
Yao TC, Huang YW, Chang SM, Tsai SY, Wu AC, Tsai HJ
Ann Intern Med: 31 Aug 2020; 173:325-330 | PMID: 32628532
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Impact:
Abstract

Clinical Benefits, Harms, and Cost-Effectiveness of Breast Cancer Screening for Survivors of Childhood Cancer Treated With Chest Radiation : A Comparative Modeling Study.

Yeh JM, Lowry KP, Schechter CB, Diller LR, ... Trentham-Dietz A, Stout NK
Background
Surveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain.
Objective
To compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors.
Design
Collaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models.
Data sources
Childhood Cancer Survivor Study and published data.
Target population
Women aged 20 years with a history of chest radiotherapy.
Time horizon
Lifetime.
Perspective
Payer.
Intervention
Annual MRI with or without mammography, starting at age 25, 30, or 35 years.
Outcome measures
Breast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs).
Results of base-case analysis
Lifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred.
Results of sensitivity analysis
Assuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged.
Limitation
Elevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986.
Conclusion
Early initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer.
Primary funding source
American Cancer Society and National Institutes of Health.



Ann Intern Med: 31 Aug 2020; 173:331-341
Yeh JM, Lowry KP, Schechter CB, Diller LR, ... Trentham-Dietz A, Stout NK
Ann Intern Med: 31 Aug 2020; 173:331-341 | PMID: 32628531
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Impact:
Abstract

Addressing Patient Bias Toward Health Care Workers: Recommendations for Medical Centers.

Paul-Emile K, Critchfield JM, Wheeler M, de Bourmont S, Fernandez A

Some patients engage in behavior or use language that demeans clinicians on the basis of their social identity traits, such as race, ethnicity, sex, disability, gender presentation, and sexual orientation, and some patients even request reassignment of involved clinicians. Despite the importance and prevalence of this problem, many medical centers lack an organizational approach for addressing patient conduct. Policy development can be daunting because organizations may encounter various barriers, including reluctance of staff to have difficult conversations about race or other identity traits; uncertainty about what constitutes an appropriate response to the spectrum of demeaning behaviors and who should make this determination; what, if any, support should be offered to targeted clinicians; whether these incidents should be reported and to whom; and whether the medical center\'s response should differ depending on whether nurses, trainees, or other clinicians are involved. These determinations have important implications for patients\' informed consent rights, clinicians\' employment rights, and medical centers\' obligations to protect patients\' health while adhering to workplace antidiscrimination laws and institutional commitments to diversity, equality, and inclusion. This article addresses these considerations and offers guidance to organizations on devising effective policies that meet the needs of medical centers, patients, and health care workers across services and roles, including physicians, nurses, and trainees.



Ann Intern Med: 14 Sep 2020; 173:468-473
Paul-Emile K, Critchfield JM, Wheeler M, de Bourmont S, Fernandez A
Ann Intern Med: 14 Sep 2020; 173:468-473 | PMID: 32658573
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Impact:
Abstract

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

Sumida K, Nadkarni GN, Grams ME, Sang Y, ... Polkinghorne KR, Heerspink HJL
Background
Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead.
Objective
To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging.
Design
Individual participant-based meta-analysis.
Setting
12 research and 21 clinical cohorts.
Participants
919 383 adults with same-day measures of ACR and PCR or dipstick protein.
Measurements
Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g).
Results
Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR.
Limitation
Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample.
Conclusion
Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis.
Primary funding source
National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.



Ann Intern Med: 14 Sep 2020; 173:426-435
Sumida K, Nadkarni GN, Grams ME, Sang Y, ... Polkinghorne KR, Heerspink HJL
Ann Intern Med: 14 Sep 2020; 173:426-435 | PMID: 32658569
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Impact:
Abstract

Institutional Review Board Quality, Private Equity, and Promoting Ethical Human Subjects Research.

Lynch HF, Rosenfeld S

Evaluating the quality and effectiveness of the institutional review boards (IRBs) responsible for overseeing research involving human participants is critically important but perpetually challenging. Seemingly common-sense measures, such as the number of proposals approved with and without major modifications and the number of unexpected adverse events occurring in approved protocols, can be misleading indicators of participant protection, and regulatory compliance may not correspond to achieving ethical goals. These measurement challenges make it difficult to assess the validity of concerns about different IRB models. A group of U.S. senators recently raised questions about the increasing use of for-profit IRBs to review research proposals (as opposed to boards typically housed at academic medical centers and health care institutions) and, more specifically, about the growing trend of private equity ownership and consolidation of for-profit IRBs. Although all IRBs face pressure to speed reviews and none are entirely free of conflicts of interest, the private equity model is particularly susceptible to approaches that could undercut the ethical mission of IRBs to protect and promote the rights and welfare of research participants. Ideally, the quality of board oversight could be measured directly, rather than relying on the heuristic of board type; this article describes several current efforts toward this goal. In the meantime, one improvement may be to pursue a new model of IRB oversight: independent nonprofit boards that stand apart from research institutions, take advantage of business approaches to research review, and minimize conflicts of interest.



Ann Intern Med: 05 Oct 2020; 173:558-562
Lynch HF, Rosenfeld S
Ann Intern Med: 05 Oct 2020; 173:558-562 | PMID: 32687743
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Impact:
Abstract

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study.

Douros A, Lix LM, Fralick M, Dell\'Aniello S, ... Ernst P, Filion KB
Background
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA).
Objective
To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes.
Design
Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221).
Setting
Electronic health care databases from 7 Canadian provinces and the United Kingdom.
Patients
208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors.
Measurements
Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin.
Results
Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk.
Limitations
There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites.
Conclusion
SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect.
Primary funding source
Canadian Institutes of Health Research.



Ann Intern Med: 14 Sep 2020; 173:417-425
Douros A, Lix LM, Fralick M, Dell'Aniello S, ... Ernst P, Filion KB
Ann Intern Med: 14 Sep 2020; 173:417-425 | PMID: 32716707
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Impact:
Abstract

Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis : A Population-Based Cohort Study.

Lyu H, Yoshida K, Zhao SS, Wei J, ... Tang P, Solomon DH
Background
Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect.
Objective
To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time.
Design
Population-based cohort study.
Setting
The Health Improvement Network U.K. primary care database, 2010 to 2019.
Patients
Persons aged 45 years or older who initiated denosumab therapy for osteoporosis.
Measurements
Observational data were used to emulate an analysis of a hypothetical trial with 3 dosing intervals: subsequent denosumab injection given within 4 weeks after the recommended date (\"on time\"), delay by 4 to 16 weeks (\"short delay\"), and delay by more than 16 weeks (\"long delay\"). The primary outcome was a composite of all fracture types at 6 months after the recommended date. Secondary outcomes were major osteoporotic fracture, vertebral fracture, hip fracture, and nonvertebral fracture.
Results
Investigators identified 2594 patients initiating denosumab therapy. The risk for composite fracture over 6 months was 27.3 in 1000 for on-time dosing, 32.2 in 1000 for short delay, and 42.4 in 1000 for long delay. Compared with on-time injections, short delay had a hazard ratio (HR) for composite fracture of 1.03 (95% CI, 0.63 to 1.69) and long delay an HR of 1.44 (CI, 0.96 to 2.17) ( for trend = 0.093). For vertebral fractures, short delay had an HR of 1.48 (CI, 0.58 to 3.79) and long delay an HR of 3.91 (CI, 1.62 to 9.45).
Limitation
Dosing schedules were not randomly assigned.
Conclusion
Although delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with long delay.
Primary funding source
National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation.



Ann Intern Med: 05 Oct 2020; 173:516-526
Lyu H, Yoshida K, Zhao SS, Wei J, ... Tang P, Solomon DH
Ann Intern Med: 05 Oct 2020; 173:516-526 | PMID: 32716706
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Impact:
Abstract

Postmarketing Safety of Vaccines Approved by the U.S. Food and Drug Administration : A Cohort Study.

Tau N, Yahav D, Shepshelovich D
Background
Vaccines are one of the greatest achievements in public health. Prevalence and clinical significance of emerging postapproval, vaccine-related safety issues have not been systematically studied.
Objective
To explore postmarketing safety modifications in U.S. Food and Drug Administration (FDA)-approved vaccine labels.
Design
Retrospective cohort study.
Setting
United States.
Participants
Initial and subsequent labels of all vaccines that were FDA-approved between 1 January 1996 and 31 December 2015.
Measurements
The primary aim was a descriptive analysis of the prevalence and characteristics of postapproval, safety-related label changes. The secondary aim was to describe the distribution of data sources triggering these modifications.
Results
The study cohort comprised 57 FDA-approved vaccines. Initial approval for 53 (93%) of the vaccines was supported by randomized controlled trials, with a median cohort size of 4161 participants (interquartile range, 2204 to 8634 participants). There were 58 postapproval, safety-related label modifications associated with 25 vaccines (49 warnings and precautions, 8 contraindications, and 1 safety-related withdrawal). The initial approval trial characteristics were similar in vaccines with and without postmarketing, safety-related label modifications. The most common safety issue triggering label modifications was expansion of population restrictions ( = 21 [36%]), followed by allergies ( = 13 [22%]). The most common source of safety data was postmarketing surveillance ( = 28 of 58 [48%]).
Limitation
The data source of the initial signal triggering safety-related label changes may not necessarily represent all safety data received and processed by the FDA.
Conclusion
Over a 20-year period, vaccines were found to be remarkably safe. A large proportion of safety issues were identified through existing postmarketing surveillance programs and were of limited clinical significance. These findings confirm the robustness of the vaccine approval system and postmarketing surveillance.
Primary funding source
None.



Ann Intern Med: 14 Sep 2020; 173:445-449
Tau N, Yahav D, Shepshelovich D
Ann Intern Med: 14 Sep 2020; 173:445-449 | PMID: 32716700
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Impact:
Abstract

Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection: A Retrospective Cohort Study.

Anderson MR, Geleris J, Anderson DR, Zucker J, ... Ferrante AW, Baldwin MR
Background
Obesity is a risk factor for pneumonia and acute respiratory distress syndrome.
Objective
To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in coronavirus disease 2019 (COVID-19).
Design
Retrospective cohort study.
Setting
A quaternary academic medical center and community hospital in New York City.
Participants
2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation.
Measurements
Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis.
Results
Over a median hospital length of stay of 7 days (interquartile range, 3 to 14) days, 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 [95% CI, 1.1 to 2.1]). This association was primarily observed among patients younger than 65 years and not in older patients ( for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis.
Limitations
Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias.
Conclusion
Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older.
Primary funding source
National Institutes of Health.



Ann Intern Med: 28 Jul 2020; epub ahead of print
Anderson MR, Geleris J, Anderson DR, Zucker J, ... Ferrante AW, Baldwin MR
Ann Intern Med: 28 Jul 2020; epub ahead of print | PMID: 32726151
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Impact:
Abstract

Chronic Obstructive Pulmonary Disease.

Labaki WW, Rosenberg SR

Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and progressive airflow obstruction. Tobacco smoking is the leading cause but not the only one. A postbronchodilator FEV-FVC ratio less than 0.70 is required for a diagnosis of COPD. Inhaler therapy is the backbone of treatment and should be complemented by a multifaceted management strategy that includes counseling and pharmacotherapy for smoking cessation, pulmonary rehabilitation, treatment of comorbidities, administration of influenza and pneumococcal immunizations, and prescription of long-term oxygen therapy in hypoxemic patients.



Ann Intern Med: 03 Aug 2020; 173:ITC17-ITC32
Labaki WW, Rosenberg SR
Ann Intern Med: 03 Aug 2020; 173:ITC17-ITC32 | PMID: 32745458
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Impact:
Abstract

Management Options for an Older Adult With Advanced Chronic Kidney Disease and Dementia: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Burns RB, Waikar SS, Wachterman MW, Kanjee Z

About 15% of adults in the United States-37 million persons-have chronic kidney disease (CKD). Chronic kidney disease is divided into 5 groups, ranging from stage 1 to stage 5 CKD, whereas end-stage kidney disease (ESKD) is defined as permanent kidney failure. The treatment options for ESKD are kidney replacement therapy (KRT) and conservative management. The options for KRT include hemodialysis (either in-center or at home), peritoneal dialysis, and kidney transplant. Conservative management, a multidisciplinary model of care for patients with stage 5 CKD who want to avoid dialysis, is guided by patient values, preferences, and goals, with a focus on quality of life and symptom management. In 2015, the Kidney Disease Outcomes Quality Initiative recommended that patients with an estimated glomerular filtration rate below 30 mL/min/1.73 m be educated about options for both KRT and conservative management. In 2018, the National Institute for Health and Care Excellence recommended that assessment for KRT or conservative management start at least 1 year before the need for therapy. It also recommended that in choosing a management approach, predicted quality of life, predicted life expectancy, patient preferences, and other patient factors be considered, because little difference in outcomes has been found among options. Here, 2 experts-a nephrologist and a general internist-palliative care physician-reflect on the care of a patient with advanced CKD and mild to moderate dementia. They discuss the management options for patients with advanced CKD, the pros and cons of each method, and how to help a patient choose among the options.



Ann Intern Med: 03 Aug 2020; 173:217-225
Burns RB, Waikar SS, Wachterman MW, Kanjee Z
Ann Intern Med: 03 Aug 2020; 173:217-225 | PMID: 32745449
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Impact:
Abstract

Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement : Exploratory Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.

Schieker M, Conaghan PG, Mindeholm L, Praestgaard J, ... Roubenoff R, Ridker PM
Background
Osteoarthritis is a common inflammatory disorder with no disease-modifying therapies. Whether inhibition of interleukin-1β (IL-1β) can reduce the consequences of large joint osteoarthritis is unclear.
Objective
To determine whether IL-1β inhibition with canakinumab reduces incident total hip or knee replacement (THR/TKR).
Design
Exploratory analysis of a randomized trial. (ClinicalTrials.gov: NCT01327846).
Setting
1091 clinical sites in 39 countries.
Participants
10 061 CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) participants.
Intervention
Random allocation to placebo or canakinumab (50, 150, or 300 mg) subcutaneously once every 3 months.
Measurements
The primary and secondary outcomes were time to first incident THR/TKR and time to first occurrence of an osteoarthritis-related adverse event (AE). Data were obtained through blinded ascertainment of trial clinical and safety databases.
Results
Median follow-up was 3.7 years. For the individual canakinumab dose groups, compared with placebo, hazard ratios (HRs) for incident THR/TKR during follow-up were 0.60 (95% CI, 0.38 to 0.95) for the 50-mg group, 0.53 (CI, 0.33 to 0.84) for the 150-mg group, and 0.60 (CI, 0.38 to 0.93) for the 300-mg group. Thus, in the pooled canakinumab groups, compared with the placebo group, incidence rates for THR/TKR were 0.31 and 0.54 events per 100 person-years (HR, 0.58 [CI, 0.42 to 0.80];  = 0.001), respectively. The HR for the secondary end point of osteoarthritis-related AEs was 0.73 (CI, 0.61 to 0.87). Similar findings were observed in analyses restricted to participants with a history of osteoarthritis.
Limitation
Because the parent trial was not designed to examine the efficacy of IL-1β inhibitors in osteoarthritis, information on structural joint outcomes was not collected.
Conclusion
Findings from this exploratory analysis of a randomized controlled trial support further investigation of IL-1β inhibition for treatment of large joint osteoarthritis.
Primary funding source
Novartis Pharmaceuticals.



Ann Intern Med: 05 Oct 2020; 173:509-515
Schieker M, Conaghan PG, Mindeholm L, Praestgaard J, ... Roubenoff R, Ridker PM
Ann Intern Med: 05 Oct 2020; 173:509-515 | PMID: 32744862
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Impact:
Abstract

Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China : A Prospective Cohort Study.

Luo L, Liu D, Liao X, Wu X, ... Ma Y, Mao C
Background
Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated.
Objective
To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings.
Design
Prospective cohort study.
Setting
Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China.
Participants
3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected.Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated.
Results
Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in healthcare settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0 to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]).
Limitation
There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts.
Conclusion
Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases.
Primary funding source
Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.



Ann Intern Med: 12 Aug 2020; epub ahead of print
Luo L, Liu D, Liao X, Wu X, ... Ma Y, Mao C
Ann Intern Med: 12 Aug 2020; epub ahead of print | PMID: 32790510
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Impact:
Abstract

Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization.

Tartof SY, Qian L, Hong V, Wei R, ... Naik TK, Murali SB
Background
Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects.
Objective
To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19.
Design
Retrospective cohort study.
Setting
Kaiser Permanente Southern California, a large integrated health care organization.
Patients
Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020.
Measurements
Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex.
Results
Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m, those with BMIs of 40 to 44 kg/m and greater than 45 kg/m had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected.
Limitation
Deaths occurring outside a health care setting and not captured in membership files may have been missed.
Conclusion
Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention.
Primary funding source
Roche-Genentech.



Ann Intern Med: 11 Aug 2020; epub ahead of print
Tartof SY, Qian L, Hong V, Wei R, ... Naik TK, Murali SB
Ann Intern Med: 11 Aug 2020; epub ahead of print | PMID: 32783686
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Impact:
Abstract

Association Between Bariatric Surgery and All-Cause Mortality: A Population-Based Matched Cohort Study in a Universal Health Care System.

Doumouras AG, Hong D, Lee Y, Tarride JE, Paterson JM, Anvari M
Background
Mortality after bariatric surgery has been previously studied, but cohort selection bias, completeness of follow-up, and collection of confounders have limited the inference of results.
Objective
To determine the association between bariatric surgery and all-cause mortality.
Design
Population-based matched cohort study.
Setting
Ontario, Canada.
Participants
13 679 patients who underwent bariatric surgery from January 2010 to December 2016 and 13 679 matched nonsurgical patients.
Intervention
Bariatric surgery.
Measurements
The primary outcome was all-cause mortality, with cause-specific mortality as the secondary outcome. Patients were matched according to age, sex, body mass index, and diabetes duration.
Results
13 679 patients who underwent bariatric surgery were matched to 13 679 nonsurgical patients. After a median follow-up of 4.9 years, the overall mortality rate was 1.4% ( = 197) in the surgery group and 2.5% ( = 340) in the nonsurgery group, with a lower adjusted hazard ratio (HR) of overall all-cause mortality (HR, 0.68 [95% CI, 0.57 to 0.81]). Patients aged 55 years or older had an absolute risk reduction of 3.3% (CI, 2.3% to 4.3%), with a lower HR of mortality in the surgery group (HR, 0.53 [CI, 0.41 to 0.69]). Observed relative effects were similar across sex; however, the observed association in absolute terms was greater in men. Surgery also was associated with lower cardiovascular mortality (HR, 0.53 [CI, 0.34 to 0.84]) and lower cancer mortality (HR, 0.54 [CI, 0.36 to 0.80]).
Limitation
The observational design limits causal inference.
Conclusion
Bariatric surgery was associated with substantially lower all-cause, cardiovascular, and cancer mortality. The lowered observed mortality of surgery was significant across most subgroups. The largest absolute effects were for men and patients aged 55 years or older.
Primary funding source
Ontario Bariatric Network.



Ann Intern Med: 17 Aug 2020; epub ahead of print
Doumouras AG, Hong D, Lee Y, Tarride JE, Paterson JM, Anvari M
Ann Intern Med: 17 Aug 2020; epub ahead of print | PMID: 32805135
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Impact:
Abstract

Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension : A Randomized Clinical Trial.

Schiavon CA, Bhatt DL, Ikeoka D, Santucci EV, ... Cavalcanti AB, Drager LF
Background
Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain.
Objective
To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone.
Design
Randomized clinical trial. (ClinicalTrials.gov: NCT01784848).
Setting
Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil.
Participants
Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m were randomly assigned (1:1 ratio).
Intervention
RYGB plus MT or MT alone.
Measurements
The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg).
Results
Among 100 patients (76% female; mean BMI, 36.9 kg/m [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03];0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively ( 0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B and 2 patients required reoperation.
Limitation
Single-center, nonblinded trial.
Conclusion
RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity.
Primary funding source
Ethicon, represented in Brazil by Johnson & Johnson do Brasil.



Ann Intern Med: 17 Aug 2020; epub ahead of print
Schiavon CA, Bhatt DL, Ikeoka D, Santucci EV, ... Cavalcanti AB, Drager LF
Ann Intern Med: 17 Aug 2020; epub ahead of print | PMID: 32805133
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Impact:
Abstract

Predictors of Prolonged Opioid Use After Initial Prescription for Acute Musculoskeletal Injuries in Adults : A Systematic Review and Meta-analysis of Observational Studies.

Riva JJ, Noor ST, Wang L, Ashoorion V, ... Couban R, Busse JW
Background
Opioids are frequently prescribed for acute musculoskeletal injuries and may result in long-term use and consequent harms.
Purpose
To explore factors associated with persistent opioid use after its prescription for acute musculoskeletal injury.
Data sources
Searches of multiple electronic databases, without language restrictions, from inception to 6 January 2020, and reference lists of selected articles.
Study selection
Observational studies of adults with opioid prescriptions for outpatient acute musculoskeletal injuries, in an adjusted model, that explored risk factors for prolonged use.
Data extraction
6 reviewers, working in pairs, independently extracted data, rated the quality of studies, and evaluated the certainty of evidence.
Data synthesis
14 cohorts with 13 263 393 participants were included. The overall prevalence of prolonged opioid use after musculoskeletal injury for high-risk populations (that is, patients receiving workers\' compensation benefits, Veterans Affairs claimants, or patients with high rates of concurrent substance use disorder) was 27% (95% CI, 18% to 37%). The prevalence among low-risk populations was 6% (CI, 4% to 8%;for interaction < 0.001). Moderate-certainty evidence showed increased odds of persistent opioid use with older age (absolute risk increase [ARI] for every 10-year increase, 1.1% [CI, 0.7% to 1.5%]) and physical comorbidity (ARI, 0.9% [CI, 0.1% to 1.7%]). Low-certainty evidence suggested increased risk for persistent opioid use with past or current substance use disorder (ARI, 10.5% [CI, 4.2% to 19.8%]), prescriptions lasting more than 7 days (median ARI, 4.5%), and higher morphine milligram equivalents per day.
Limitation
Sparse, heterogeneous data with suboptimal adjustment for potential confounders.
Conclusion
Avoiding prescribing opioids for acute musculoskeletal injuries to patients with past or current substance use disorder, and restricting duration to 7 days or less and using lower doses when they are prescribed, are potentially important targets to reduce rates of persistent opioid use.
Primary funding source
National Safety Council. (PROSPERO: CRD42018104968).



Ann Intern Med: 17 Aug 2020; epub ahead of print
Riva JJ, Noor ST, Wang L, Ashoorion V, ... Couban R, Busse JW
Ann Intern Med: 17 Aug 2020; epub ahead of print | PMID: 32805130
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Impact:
Abstract

Management of Acute Pain From Non-Low Back Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

Busse JW, Sadeghirad B, Oparin Y, Chen E, ... Das A, Guyatt GH
Background
Patients and clinicians can choose from several treatment options to address acute pain from non-low back musculoskeletal injuries.
Purpose
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
Data sources
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
Study selection
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks\' duration from non-low back musculoskeletal injuries.
Data extraction
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
Data synthesis
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
Limitations
Only English-language studies were included. The number of head-to-head comparisons was limited.
Conclusion
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
Primary funding source
National Safety Council. (PROSPERO: CRD42018094412).



Ann Intern Med: 17 Aug 2020; epub ahead of print
Busse JW, Sadeghirad B, Oparin Y, Chen E, ... Das A, Guyatt GH
Ann Intern Med: 17 Aug 2020; epub ahead of print | PMID: 32805127
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Abstract

Nonpharmacologic and Pharmacologic Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries in Adults: A Clinical Guideline From the American College of Physicians and American Academy of Family Physicians.

Qaseem A, McLean RM, O\'Gurek D, Batur P, Lin K, Kansagara DL
Description
The American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) developed this guideline to provide clinical recommendations on nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults in the outpatient setting. The guidance is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. This guideline does not address noninvasive treatment of low back pain, which is covered by a separate ACP guideline that has also been endorsed by AAFP.
Methods
This guideline is based on a systematic evidence review on the comparative efficacy and safety of nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults in the outpatient setting and a systematic review on the predictors of prolonged opioid use. We evaluated the following clinical outcomes using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system: pain (at ≤2 hours and at 1 to 7 days), physical function, symptom relief, treatment satisfaction, and adverse events.
Target audience and patient population
The target audience is all clinicians, and the target patient population is adults with acute pain from non-low back, musculoskeletal injuries.
Recommendation 1

Recommendation 2a

Recommendation 2b

Recommendation 3




Ann Intern Med: 17 Aug 2020; epub ahead of print
Qaseem A, McLean RM, O'Gurek D, Batur P, Lin K, Kansagara DL
Ann Intern Med: 17 Aug 2020; epub ahead of print | PMID: 32805126
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Impact:
Abstract

Addressing Postpandemic Clinician Mental Health : A Narrative Review and Conceptual Framework.

Schwartz R, Sinskey JL, Anand U, Margolis RD

Previous pandemics have seen high psychiatric morbidity among health care workers. Protecting clinician mental health in the aftermath of coronavirus disease 2019 (COVID-19) requires an evidence-based approach to developing and deploying comprehensive clinician mental health support. In a narrative review of 96 articles addressing clinician mental health in COVID-19 and prior pandemics, 7 themes emerged: 1) the need for resilience and stress reduction training; 2) providing for clinicians\' basic needs (food, drink, adequate rest, quarantine-appropriate housing, transportation, child care, personal protective equipment); 3) the importance of specialized training for pandemic-induced changes in job roles; 4) recognition and clear communication from leadership; 5) acknowledgment of and strategies for addressing moral injury; 6) the need for peer and social support interventions; and 7) normalization and provision of mental health support programs. In addition to the literature review, in collaboration with the Collaborative for Healing and Renewal in Medicine (CHARM) network, the authors gathered practice guidelines and resources from health care organizations and professional societies worldwide to synthesize a list of resources deemed high-yield by well-being leaders. Studies of previous pandemics demonstrate heightened distress in health care workers years after the event. The COVID-19 pandemic presents unique challenges that surpass those of previous pandemics, suggesting a significant mental health toll on clinicians. Long-term, proactive individual, organizational, and societal infrastructures for clinician mental health support are needed to mitigate the psychological costs of providing care during the COVID-19 pandemic.



Ann Intern Med: 20 Aug 2020; epub ahead of print
Schwartz R, Sinskey JL, Anand U, Margolis RD
Ann Intern Med: 20 Aug 2020; epub ahead of print | PMID: 32822206
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Impact:
Abstract

Acute Cardiovascular Events Associated With Influenza in Hospitalized Adults : A Cross-sectional Study.

Chow EJ, Rolfes MA, O\'Halloran A, Anderson EJ, ... Reed C, Garg S
Background
Influenza may contribute to the burden of acute cardiovascular events during annual influenza epidemics.
Objective
To examine acute cardiovascular events and determine risk factors for acute heart failure (aHF) and acute ischemic heart disease (aIHD) in adults with a hospitalization associated with laboratory-confirmed influenza.
Design
Cross-sectional study.
Setting
U.S. Influenza Hospitalization Surveillance Network during the 2010-to-2011 through 2017-to-2018 influenza seasons.
Participants
Adults hospitalized with laboratory-confirmed influenza and identified through influenza testing ordered by a practitioner.
Measurements
Acute cardiovascular events were ascertained using discharge codes from the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, and ICD, 10th Revision. Age, sex, race/ethnicity, tobacco use, chronic conditions, influenza vaccination, influenza antiviral medication, and influenza type or subtype were included as exposures in logistic regression models, and marginal adjusted risk ratios and 95% CIs were estimated to describe factors associated with aHF or aIHD.
Results
Among 89 999 adults with laboratory-confirmed influenza, 80 261 had complete medical record abstractions and available ICD codes (median age, 69 years [interquartile range, 54 to 81 years]) and 11.7% had an acute cardiovascular event. The most common such events (non-mutually exclusive) were aHF (6.2%) and aIHD (5.7%). Older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease were significantly associated with higher risk for aHF and aIHD in adults hospitalized with laboratory-confirmed influenza.
Limitation
Underdetection of cases was likely because influenza testing was based on practitioner orders. Acute cardiovascular events were identified by ICD discharge codes and may be subject to misclassification bias.
Conclusion
In this population-based study of adults hospitalized with influenza, almost 12% of patients had an acute cardiovascular event. Clinicians should ensure high rates of influenza vaccination, especially in those with underlying chronic conditions, to protect against acute cardiovascular events associated with influenza.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 24 Aug 2020; epub ahead of print
Chow EJ, Rolfes MA, O'Halloran A, Anderson EJ, ... Reed C, Garg S
Ann Intern Med: 24 Aug 2020; epub ahead of print | PMID: 32833488
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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: 31 Aug 2020; epub ahead of print
D'Anci KE, Tipton K, Hedden-Gross A, Rouse B, Hermanson L, Fontanarosa J
Ann Intern Med: 31 Aug 2020; epub ahead of print | PMID: 32866419
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Impact:
Abstract

Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring : A Cohort Study.

Ludvigsson JF, Winell H, Sandin S, Cnattingius S, Stephansson O, Pasternak B
Background
There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD).
Objective
To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 (\"swine flu\") during pregnancy.
Design
Population-based cohort study using nationwide registers.
Setting
Seven health care regions in Sweden.
Participants
Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed.
Measurements
Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD).
Results
Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, -0.09% to 0.17%) for ASD and 0.02% (CI, -0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD).
Limitation
Data on H1N1 influenza infection are lacking.
Conclusion
This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring.
Primary funding source
Swedish Research Council.



Ann Intern Med: 31 Aug 2020; epub ahead of print
Ludvigsson JF, Winell H, Sandin S, Cnattingius S, Stephansson O, Pasternak B
Ann Intern Med: 31 Aug 2020; epub ahead of print | PMID: 32866418
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Impact:
Abstract

Synopsis of the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Clinical Practice Guideline: The Diagnosis and Management of Hypertension in the Primary Care Setting.

Tschanz CMP, Cushman WC, E Harrell CT, Berlowitz DR, Sall JL
Description
In January 2020, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the diagnosis and management of hypertension in the primary care setting.
Methods
The VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included a multidisciplinary panel of practicing clinician stakeholders and conformed to the Institute of Medicine\'s tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions in collaboration with the ECRI Institute, which systematically searched and evaluated the literature from 15 December 2013 to 25 March 2019 and developed and rated recommendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
Recommendations
This synopsis summarizes key features of the guideline in several key areas: the measurement of blood pressure, the definition of hypertension, target treatment goals, and nonpharmacologic and pharmacologic treatment of essential and resistant hypertension.



Ann Intern Med: 31 Aug 2020; epub ahead of print
Tschanz CMP, Cushman WC, E Harrell CT, Berlowitz DR, Sall JL
Ann Intern Med: 31 Aug 2020; epub ahead of print | PMID: 32866417
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Impact:
Abstract

Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association\'s Standards of Medical Care in Diabetes Clinical Guideline.

Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J
Description
The American Diabetes Association (ADA) updates the Standards of Medical Care in Diabetes annually to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of diabetes.
Methods
To develop the 2020 Standards, the ADA Professional Practice Committee, comprising physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts, continuously searched MEDLINE (English language only) from 15 October 2018 through August-September 2019 for pertinent studies, including high-quality trials that addressed pharmacologic management of type 2 diabetes. The committee selected and reviewed the studies, developed the recommendations, and solicited feedback from the larger clinical community.
Recommendations
This synopsis focuses on guidance relating to the pharmacologic treatment of adults with type 2 diabetes. Recommendations address oral and noninsulin injectable therapies, insulin treatment, and combination injectable therapies. Results of recent large trials with cardiovascular and renal outcomes are emphasized.



Ann Intern Med: 31 Aug 2020; epub ahead of print
Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J
Ann Intern Med: 31 Aug 2020; epub ahead of print | PMID: 32866414
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Impact:
Abstract

Deep Learning Using Chest Radiographs to Identify High-Risk Smokers for Lung Cancer Screening Computed Tomography: Development and Validation of a Prediction Model.

Lu MT, Raghu VK, Mayrhofer T, Aerts HJWL, Hoffmann U
Background
Lung cancer screening with chest computed tomography (CT) reduces lung cancer death. Centers for Medicare & Medicaid Services (CMS) eligibility criteria for lung cancer screening with CT require detailed smoking information and miss many incident lung cancers. An automated deep-learning approach based on chest radiograph images may identify more smokers at high risk for lung cancer who could benefit from screening with CT.
Objective
To develop and validate a convolutional neural network (CXR-LC) that predicts long-term incident lung cancer using data commonly available in the electronic medical record (EMR) (chest radiograph, age, sex, and whether currently smoking).
Design
Risk prediction study.
Setting
U.S. lung cancer screening trials.
Participants
The CXR-LC model was developed in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial ( = 41 856). The final CXR-LC model was validated in additional PLCO smokers ( = 5615, 12-year follow-up) and NLST (National Lung Screening Trial) heavy smokers ( = 5493, 6-year follow-up). Results are reported for validation data sets only.
Measurements
Up to 12-year lung cancer incidence predicted by CXR-LC.
Results
The CXR-LC model had better discrimination (area under the receiver-operating characteristic curve [AUC]) for incident lung cancer than CMS eligibility (PLCO AUC, 0.755 vs. 0.634;< 0.001). The CXR-LC model\'s performance was similar to that of PLCO, a state-of-the-art risk score with 11 inputs, in both the PLCO data set (CXR-LC AUC of 0.755 vs. PLCO AUC of 0.751) and the NLST data set (0.659 vs. 0.650). When compared in equal-sized screening populations, CXR-LC was more sensitive than CMS eligibility in the PLCO data set (74.9% vs. 63.8%;= 0.012) and missed 30.7% fewer incident lung cancers. On decision curve analysis, CXR-LC had higher net benefit than CMS eligibility and similar benefit to PLCO.
Limitation
Validation in lung cancer screening trials and not a clinical setting.
Conclusion
The CXR-LC model identified smokers at high risk for incident lung cancer, beyond CMS eligibility and using information commonly available in the EMR.
Primary funding source
None.



Ann Intern Med: 31 Aug 2020; epub ahead of print
Lu MT, Raghu VK, Mayrhofer T, Aerts HJWL, Hoffmann U
Ann Intern Med: 31 Aug 2020; epub ahead of print | PMID: 32866413
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Impact:
Abstract

Hepatitis C Virus.

Kaplan DE

Hepatitis C virus (HCV) is the most common bloodborne pathogen in the United States, chronically affecting approximately 2.4 million Americans, most of whom are unaware of the infection. Highly effective, well-tolerated therapies are now available with markedly simplified treatment algorithms. Eradication of HCV is a national goal. Increased efforts to extend access to treatment to populations that traditionally are difficult to treat, such as persons who inject drugs, are critical to achieving eradication. Given the magnitude of the disease burden, an increased role of primary care providers in screening, patient stratification, and treatment will be needed.



Ann Intern Med: 31 Aug 2020; 173:ITC33-ITC48
Kaplan DE
Ann Intern Med: 31 Aug 2020; 173:ITC33-ITC48 | PMID: 32866406
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Impact:
Abstract

Toward Historical Accountability and Remembrance: The German Society for Internal Medicine and Its Legacies From the Nazi Past.

Hofer HG, Forsbach R, Fölsch UR

After decades of silence, the German Society for Internal Medicine (DGIM) has made considerable efforts to come to terms with its role and actions during the Nazi era (1933 to 1945). This is particularly important because, with more than 27 000 members, the DGIM is the largest medical society in present-day Germany. Since 1882, the society\'s annual congress in Wiesbaden has provided a forum and focus for the key medical topics of the day. Based on ongoing historical research, this article is organized in 2 parts. The first describes how the DGIM willingly adapted to the ideology and politics of the Nazi regime, showing no solidarity with its persecuted Jewish members. To illustrate their fates, the cases of Leopold Lichtwitz, who was forced to resign as elected chairman in 1933, and committee member Julius Bauer are investigated. Both men emigrated to the United States. Light is also shed on the decisions of those who led the society during the Nazi era and on the involvement of high-ranking members in medical crimes. The second part of the article analyzes developments in the postwar period and considers why it took so long to hold up a mirror to the past. Although critical voices could be heard from both outside and within the society, they remained isolated and without consequence. Only the past 2 decades have brought about both general and specific developments toward historical accountability and an active culture of remembrance. With a declaration first published in 2015, a new website bringing history and memory together, and a strong commitment to the norms and values of liberal democracy, the DGIM has found its way to a clear position-and has lessons to teach.



Ann Intern Med: 31 Aug 2020; 173:375-379
Hofer HG, Forsbach R, Fölsch UR
Ann Intern Med: 31 Aug 2020; 173:375-379 | PMID: 32866400
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Impact:
Abstract

Probable Evidence of Fecal Aerosol Transmission of SARS-CoV-2 in a High-Rise Building.

Kang M, Wei J, Yuan J, Guo J, ... Li Y, Zhong N
Background
The role of fecal aerosols in the transmission of severe acute respiratory syndrome coronavirus 2 has been suspected.
Objective
To investigate the temporal and spatial distributions of 3 infected families in a high-rise apartment building and examine the associated environment variables to verify the role of fecal aerosols.
Design
Epidemiologic survey and quantitative reverse transcriptase polymerase chain reaction analyses on throat swabs from the participants; 237 surface and air samples from 11 of the 83 flats in the building, public areas, and building drainage systems; and tracer gas released into bathrooms as a surrogate for virus-laden aerosols in the drainage system.
Setting
A high-rise apartment building in Guangzhou, China.
Participants
9 infected patients, 193 other residents of the building, and 24 members of the building\'s management staff.
Measurements
Locations of infected flats and positive environmental samples, and spread of virus-laden aerosols.
Results
9 infected patients in 3 families were identified. The first family had a history of travel to the coronavirus disease 2019 (COVID-19) epicenter Wuhan, whereas the other 2 families had no travel history and a later onset of symptoms. No evidence was found for transmission via the elevator or elsewhere. The families lived in 3 vertically aligned flats connected by drainage pipes in the master bathrooms. Both the observed infections and the locations of positive environmental samples are consistent with the vertical spread of virus-laden aerosols via these stacks and vents.
Limitation
Inability to determine whether the water seals were dried out in the flats of the infected families.
Conclusion
On the basis of circumstantial evidence, fecal aerosol transmission may have caused the community outbreak of COVID-19 in this high-rise building.
Primary funding source
Key-Area Research and Development Program of Guangdong Province and the Research Grants Council of Hong Kong.



Ann Intern Med: 31 Aug 2020; epub ahead of print
Kang M, Wei J, Yuan J, Guo J, ... Li Y, Zhong N
Ann Intern Med: 31 Aug 2020; epub ahead of print | PMID: 32870707
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Impact:
Abstract

Attitudes Toward a Potential SARS-CoV-2 Vaccine: A Survey of U.S. Adults.

Fisher KA, Bloomstone SJ, Walder J, Crawford S, Fouayzi H, Mazor KM
Background
Coronavirus disease 2019 (COVID-19) has rapidly instigated a global pandemic. Vaccine development is proceeding at an unprecedented pace. Once available, it will be important to maximize vaccine uptake and coverage.
Objective
To assess intent to be vaccinated against COVID-19 among a representative sample of adults in the United States and identify predictors of and reasons for vaccine hesitancy.
Design
Cross-sectional survey, fielded from 16 through 20 April 2020.
Setting
Representative sample of adults residing in the United States.
Participants
Approximately 1000 adults drawn from the AmeriSpeak probability-based research panel, covering approximately 97% of the U.S. household population.
Measurements
Intent to be vaccinated against COVID-19 was measured with the question, \"When a vaccine for the coronavirus becomes available, will you get vaccinated?\" Response options were \"yes,\" \"no,\" and \"not sure.\" Participants who responded \"no\" or \"not sure\" were asked to provide a reason.
Results
A total of 991 AmeriSpeak panel members responded. Overall, 57.6% of participants ( = 571) intended to be vaccinated, 31.6% ( = 313) were not sure, and 10.8% ( = 107) did not intend to be vaccinated. Factors independently associated with vaccine hesitancy (a response of \"no\" or \"not sure\") included younger age, Black race, lower educational attainment, and not having received the influenza vaccine in the prior year. Reasons for vaccine hesitancy included vaccine-specific concerns, a need for more information, antivaccine attitudes or beliefs, and a lack of trust.
Limitations
Participants\' intent to be vaccinated was explored before a vaccine was available and when the pandemic was affecting a narrower swath of the United States. Questions about specific information or factors that might increase vaccination acceptance were not included. The survey response rate was 16.1%.
Conclusion
This national survey, conducted during the coronavirus pandemic, revealed that approximately 3 in 10 adults were not sure they would accept vaccination and 1 in 10 did not intend to be vaccinated against COVID-19. Targeted and multipronged efforts will be needed to increase acceptance of a COVID-19 vaccine when one becomes available.
Primary funding source
Agency for Healthcare Research and Quality.



Ann Intern Med: 03 Sep 2020; epub ahead of print
Fisher KA, Bloomstone SJ, Walder J, Crawford S, Fouayzi H, Mazor KM
Ann Intern Med: 03 Sep 2020; epub ahead of print | PMID: 32886525
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Impact:
Abstract

National Trends in Drug Payments for HIV Preexposure Prophylaxis in the United States, 2014 to 2018 : A Retrospective Cohort Study.

Furukawa NW, Zhu W, Huang YA, Shrestha RK, Hoover KW
Background
Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown.
Objective
To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database.
Design
Retrospective cohort study.
Setting
Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions.
Measurements
Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments.
Results
Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance.
Limitation
The IQVIA database does not capture every prescription nationwide.
Conclusion
Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion.
Primary funding source
Centers for Disease Control and Prevention.



Ann Intern Med: 07 Sep 2020; epub ahead of print
Furukawa NW, Zhu W, Huang YA, Shrestha RK, Hoover KW
Ann Intern Med: 07 Sep 2020; epub ahead of print | PMID: 32894696
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Impact:
Abstract

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

Faughnan ME, Mager JJ, Hetts SW, Palda VA, ... Winship I, Zarrabeitia R
Description
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications.
Methods
The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved.
Recommendations
The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.



Ann Intern Med: 07 Sep 2020; epub ahead of print
Faughnan ME, Mager JJ, Hetts SW, Palda VA, ... Winship I, Zarrabeitia R
Ann Intern Med: 07 Sep 2020; epub ahead of print | PMID: 32894695
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Impact:
Abstract

Every Body Counts: Measuring Mortality From the COVID-19 Pandemic.

Kiang MV, Irizarry RA, Buckee CO, Balsari S

As of mid-August 2020, more than 170 000 U.S. residents have died of coronavirus disease 2019 (COVID-19); however, the true number of deaths resulting from COVID-19, both directly and indirectly, is likely to be much higher. The proper attribution of deaths to this pandemic has a range of societal, legal, mortuary, and public health consequences. This article discusses the current difficulties of disaster death attribution and describes the strengths and limitations of relying on death counts from death certificates, estimations of indirect deaths, and estimations of excess mortality. Improving the tabulation of direct and indirect deaths on death certificates will require concerted efforts and consensus across medical institutions and public health agencies. In addition, actionable estimates of excess mortality will require timely access to standardized and structured vital registry data, which should be shared directly at the state level to ensure rapid response for local governments. Correct attribution of direct and indirect deaths and estimation of excess mortality are complementary goals that are critical to our understanding of the pandemic and its effect on human life.



Ann Intern Med: 10 Sep 2020; epub ahead of print
Kiang MV, Irizarry RA, Buckee CO, Balsari S
Ann Intern Med: 10 Sep 2020; epub ahead of print | PMID: 32915654
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Impact:
Abstract

Effectiveness of Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

Wang Z, Jones G, Winzenberg T, Cai G, ... Ding C, Antony B
Background
Current pharmacologic therapies for patients with osteoarthritis are suboptimal.
Objective
To determine the efficacy ofextract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis.
Design
Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224).
Setting
Single-center study with patients from southern Tasmania, Australia.
Participants
70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis.
Intervention
2 capsules of CL ( = 36) or matched placebo ( = 34) per day for 12 weeks.
Measurements
The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks.
Results
CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [ = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm];  = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL ( = 14 [39%]) and placebo ( = 18 [53%]) groups ( = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related.
Limitation
Modest sample size and short duration.
Conclusion
CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings.
Primary funding source
University of Tasmania and Natural Remedies Private Limited.



Ann Intern Med: 14 Sep 2020; epub ahead of print
Wang Z, Jones G, Winzenberg T, Cai G, ... Ding C, Antony B
Ann Intern Med: 14 Sep 2020; epub ahead of print | PMID: 32926799
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Impact:
Abstract

Policy Recommendations to Promote Prescription Drug Competition: A Position Paper From the American College of Physicians.

Daniel H, Serchen J, Cooney TG

The prescription drug market in the United States relies on competition to keep prices reasonable. Although many policies have been implemented to spur competition and decrease costs for patients, these policies may be outdated and should be redesigned and updated to achieve success in the current prescription drug market. In this paper, the American College of Physicians (ACP) proposes that new policies should be implemented to prevent market manipulation, help lower-cost alternatives make it to the market faster, and ensure a robust and competitive market for generic and biosimilar drugs. The ACP believes these changes will have a meaningful effect on patients without shifting costs to other areas of the health care system.



Ann Intern Med: 14 Sep 2020; epub ahead of print
Daniel H, Serchen J, Cooney TG
Ann Intern Med: 14 Sep 2020; epub ahead of print | PMID: 32926798
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Impact:
Abstract

Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study.

Rogers JH, Link AC, McCulloch D, Brandstetter E, ... Bedford T, Chu HY
Background
Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities.
Objective
To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area.
Design
Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917).
Setting
14 homeless shelters in King County, Washington.
Participants
A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms.
Intervention
Two strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing (\"surge testing\") events.
Measurements
The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity.
Results
Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most ( = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most ( = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room.
Limitation
Selection bias due to voluntary participation and a relatively small case count.
Conclusion
Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations.
Primary funding source
Gates Ventures.



Ann Intern Med: 14 Sep 2020; epub ahead of print
Rogers JH, Link AC, McCulloch D, Brandstetter E, ... Bedford T, Chu HY
Ann Intern Med: 14 Sep 2020; epub ahead of print | PMID: 32931328
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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 Sep 2020; epub ahead of print
Chia ML, Him Chau DH, Lim KS, Yang Liu CW, Tan HK, Tan YR
Ann Intern Med: 16 Sep 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 Sep 2020; epub ahead of print
Meyerowitz EA, Richterman A, Gandhi RT, Sax PE
Ann Intern Med: 16 Sep 2020; epub ahead of print | PMID: 32941052
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Impact:
Abstract

Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study.

George MD, Baker JF, Winthrop K, Hsu JY, ... Yun H, Curtis JR
Background
Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain.
Objective
To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy.
Design
Retrospective cohort study.
Setting
Medicare claims data and Optum\'s deidentified Clinformatics Data Mart database from 2006 to 2015.
Patients
Adults with RA receiving a stable DMARD regimen for more than 6 months.
Measurements
Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models.
Results
247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all< 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all< 0.001 vs. no glucocorticoids).
Limitation
Potential for residual confounding and misclassification of glucocorticoid dose.
Conclusion
In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk.
Primary funding source
National Institute of Arthritis and Musculoskeletal and Skin Diseases.



Ann Intern Med: 21 Sep 2020; epub ahead of print
George MD, Baker JF, Winthrop K, Hsu JY, ... Yun H, Curtis JR
Ann Intern Med: 21 Sep 2020; epub ahead of print | PMID: 32956604
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Impact:
Abstract

Distinguishing High-Performing Health Systems Using a Composite of Publicly Reported Measures of Ambulatory Care.

Agniel D, Haviland A, Shekelle P, Scherling A, Damberg CL
Background
Payers and policymakers are rewarding high-performing health care providers on the basis of summaries of overall quality performance, and the methods they use for measuring performance are increasingly important.
Objective
To develop and evaluate a measure that ranks health care systems by ambulatory care quality.
Design
Systems were ranked using a composite model that summarizes individual measures of quality, accounts for their correlation, and does not require health care systems to report every measure. The composite measure\'s suitability was evaluated by examining whether it captured the quality indicated by component measures (validity), whether differences in rank between health care systems were larger than statistical noise (reliability), and whether year-to-year changes in rank were small (stability).
Setting
California and Minnesota, 2014 to 2016.
Participants
55 health care systems.
Measurements
Publicly reported measures of ambulatory care quality.
Results
The composite measure was valid in that it was broadly representative of the component measures and was not dominated by any single measure. The measure was reliable because the ranks for 93% of California systems and 80% of Minnesota systems were unlikely to be more than 2 places lower or higher. The measure was stable because fewer than half of systems changed ranks by more than 2 ranks from year to year.
Limitation
The analysis is limited to available measures of ambulatory care quality and includes only 2 states.
Conclusion
This composite measure uses publicly reported data to produce valid, reliable, and stable ranks of ambulatory care quality for health care systems in Minnesota and California, and this approach could be used in other applications.
Primary funding source
Agency for Healthcare Research and Quality.



Ann Intern Med: 21 Sep 2020; epub ahead of print
Agniel D, Haviland A, Shekelle P, Scherling A, Damberg CL
Ann Intern Med: 21 Sep 2020; epub ahead of print | PMID: 32956603
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Impact:
Abstract

Interventions to Improve Statin Tolerance and Adherence in Patients at Risk for Cardiovascular Disease : A Systematic Review for the 2020 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Dyslipidemia.

Reston JT, Buelt A, Donahue MP, Neubauer B, Vagichev E, McShea K
Background
Strategies to improve patients\' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD).
Purpose
To assess the benefits and harms of interventions to improve statin adherence in patients at risk for CVD.
Data sources
MEDLINE, EMBASE, PubMed, and the Cochrane Library from December 2013 through May 2019 (English language only).
Study selection
Systematic reviews (SRs), randomized controlled trials (RCTs), and cohort studies that addressed interventions for improving statin tolerance and adherence.
Data extraction
One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy.
Data synthesis
One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with statin treatment discontinuation, nondaily statin dosing lowered total cholesterol and LDL-C levels. One large cohort study suggested that more than 90% of patients who discontinued statin treatment could be rechallenged with the same or a different statin and be adherent 1 year after a statin-related adverse event led to discontinuation. Two small cohort studies reported that more than 90% of patients who were previously intolerant to statins and who had low baseline levels of vitamin D were able to adhere to statins 1 year after vitamin D supplementation.
Limitation
This is a qualitative synthesis of new evidence with existing meta-analyses, and studies had several methodological shortcomings.
Conclusion
Although the strength of evidence for most interventions was low or very low, intensified patient care and rechallenge with the same or a different statin (or a lower dose) seem to be favorable options for improving statin adherence.
Primary funding source
U.S. Department of Veterans Affairs.



Ann Intern Med: 21 Sep 2020; epub ahead of print
Reston JT, Buelt A, Donahue MP, Neubauer B, Vagichev E, McShea K
Ann Intern Med: 21 Sep 2020; epub ahead of print | PMID: 32956601
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Impact:
Abstract

Prevalence of Human Papillomavirus and Estimation of Human Papillomavirus Vaccine Effectiveness in Thimphu, Bhutan, in 2011-2012 and 2018 : A Cross-sectional Study.

Baussano I, Tshomo U, Tenet V, Heideman DAM, ... Franceschi S, Clifford GM
Background
Bhutan implemented a national program for human papillomavirus (HPV) vaccination in 2010 involving girls aged 12 to 18 years and achieving nearly 90% coverage.
Objective
To estimate HPV vaccine effectiveness in a city in Bhutan.
Design
2 cross-sectional surveys, 2011-2012 and 2018.
Setting
2 hospitals in Thimphu, capital of Bhutan.
Participants
Sexually active women aged 17 to 29 years: 1445 participants from the baseline survey and 1595 from the repeated survey.
Intervention
National HPV vaccination program.
Measurements
HPV was assessed in cervical cell samples by using general primer GP5+/GP6+-mediated polymerase chain reaction. Human papillomavirus types were stratified as vaccine types (HPV6/11/16/18) and nonvaccine types. Age- and sexual behavior-adjusted overall, total, and indirect (herd immunity) vaccine effectiveness (VE) was computed as (1 - HPV prevalence ratio) for HPV among all women and among unvaccinated women.
Results
Between the 2 surveys, the prevalence of HPV vaccine types decreased from 8.3% to 1.4%, whereas the prevalence of nonvaccine types increased from 25.8% to 31.4%. The overall and indirect adjusted VE against vaccine-targeted HPV types was 88% (95% CI, 80% to 92%) and 78% (CI, 61% to 88%), respectively. Among women younger than 27 years, who were targeted by the vaccination program, the overall and indirect adjusted VE was 93% (CI, 87% to 97%) and 88% (CI, 69% to 95%), respectively. No impact on nonvaccine HPV types was detectable.
Limitation
Hospital-based recruitment; self-reported vaccination status.
Conclusion
In Bhutan, the prevalence of vaccine-targeted HPV types has decreased sharply, providing the first evidence of the effectiveness of a high-coverage national HPV vaccination program in a lower-middle-income country.
Primary funding source
Bill & Melinda Gates Foundation.



Ann Intern Med: 21 Sep 2020; epub ahead of print
Baussano I, Tshomo U, Tenet V, Heideman DAM, ... Franceschi S, Clifford GM
Ann Intern Med: 21 Sep 2020; epub ahead of print | PMID: 32956600
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Impact:
Abstract

Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

O\'Malley PG, Arnold MJ, Kelley C, Spacek L, ... Neubauer BE, Downs JR
Description
In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations.
Methods
On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine\'s tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
Recommendations
This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.



Ann Intern Med: 21 Sep 2020; epub ahead of print
O'Malley PG, Arnold MJ, Kelley C, Spacek L, ... Neubauer BE, Downs JR
Ann Intern Med: 21 Sep 2020; epub ahead of print | PMID: 32956597
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Impact:
Abstract

Patient Trajectories Among Persons Hospitalized for COVID-19 : A Cohort Study.

Garibaldi BT, Fiksel J, Muschelli J, Robinson ML, ... Zeger SL, Gupta A
Background
Risk factors for progression of coronavirus 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts.
Objective
To determine the factors on hospital admission that are predictive of severe disease or death from COVID-19.
Design
Retrospective cohort analysis.
Setting
Five hospitals in the Maryland and Washington, DC, area.
Patients
832 consecutive COVID-19 admissions from 4 March to 24 April 2020, with follow-up through 27 June 2020.
Measurements
Patient trajectories and outcomes, categorized by using the World Health Organization COVID-19 disease severity scale. Primary outcomes were death and a composite of severe disease or death.
Results
Median patient age was 64 years (range, 1 to 108 years); 47% were women, 40% were Black, 16% were Latinx, and 21% were nursing home residents. Among all patients, 131 (16%) died and 694 (83%) were discharged (523 [63%] had mild to moderate disease and 171 [20%] had severe disease). Of deaths, 66 (50%) were nursing home residents. Of 787 patients admitted with mild to moderate disease, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79, at day 2, 4, and 7, respectively.
Limitation
The study was done in a single health care system.
Conclusion
A combination of demographic and clinical variables is strongly associated with severe COVID-19 disease or death and their early onset. The COVID-19 Inpatient Risk Calculator (CIRC), using factors present on admission, can inform clinical and resource allocation decisions.
Primary funding source
Hopkins inHealth and COVID-19 Administrative Supplement for the HHS Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response.



Ann Intern Med: 21 Sep 2020; epub ahead of print
Garibaldi BT, Fiksel J, Muschelli J, Robinson ML, ... Zeger SL, Gupta A
Ann Intern Med: 21 Sep 2020; epub ahead of print | PMID: 32960645
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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: 28 Sep 2020; epub ahead of print
Ranney ML, Herges C, Metcalfe L, Schuur JD, Hain P, Rowhani-Rahbar A
Ann Intern Med: 28 Sep 2020; epub ahead of print | PMID: 32986488
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Impact:
Abstract

Ideas About Resourcing Health Care in the United States: Can Economic Evaluation Achieve Meaningful Use?

Padula WV, Sculpher MJ

The United States is one of the few high-income countries not to apply economic evaluation routinely to health care decision making on a national level, yet it excels at spending least efficiently on health care. In the interest of continuing to develop new solutions to curb spending on health care and reduce waste in the United States, perhaps now is an important moment to reconsider the benefits of economic evaluation and the barriers that must be overcome to have it emerge as a solution for health care institutions and the patients they serve. This article offers several distinct considerations to make economic evaluation methods (such as cost-effectiveness analysis) an effective component of value-based decision making in the United States. These considerations include overcoming the barriers presented by opportunity costs, spending on health care services versus biomedical technologies, phasing out low-value care, using value of information to prioritize resources, and determining what to do with the quality-adjusted life-year. These issues need to be addressed to achieve a collective purpose for economic evaluation at state and national levels.



Ann Intern Med: 28 Sep 2020; epub ahead of print
Padula WV, Sculpher MJ
Ann Intern Med: 28 Sep 2020; epub ahead of print | PMID: 32986487
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Impact:
Abstract

Key Evidence Supporting Prescription Opioids Approved by the U.S. Food and Drug Administration, 1997 to 2018.

Heyward J, Moore TJ, Chen J, Meek K, Lurie P, Alexander GC
Background
Little is known about the evidence required by the U.S. Food and Drug Administration (FDA) for new approvals of opioid analgesics.
Objective
To characterize the quality of safety and efficacy data in new drug applications (NDAs) for opioid analgesics approved by the FDA between 1997 and 2018.
Design
Cross-sectional analysis.
Setting
Data from ClinicalTrials.gov, FDA reviews, and peer-reviewed publications.
Participants
Patients with pain who participated in phase 3 pivotal trials.
Intervention
FDA-approved opioid analgesics.
Measurements
Key characteristics of each NDA, including the number, size, and duration of pivotal trials; trial control groups; the use of enriched trial populations; and systematically measured safety outcomes.
Results
Most of the 48 NDAs evaluated were for new dosage forms ( = 25 [52.1%]) or new formulations ( = 9 [18.8%]); only 1 (2.1%) was for a new molecular entity. Of 39 NDAs approved for treating chronic pain, only 21 products were supported by at least 1 pivotal trial; these trials ( = 28) had a median duration of 84 days (interquartile range [IQR], 25 to 84 days) and enrolled a median of 299 patients (IQR, 174 to 525 patients). Seventeen (81%) of these products were approved on the basis of designs that excluded patients who could not tolerate the drugs, had early adverse effects, or reported few immediate benefits. Among NDAs for chronic pain, 8 (20.5%) included pooled safety reviews that reported systematic assessment of diversion, 7 (17.9%) reported systematic measurement of nonmedical use, and 15 (38.5%) assessed development of tolerance. Eight of 9 products for acute pain were supported by at least 1 pivotal trial; the pivotal trials ( = 19) had a median duration of 1 day (IQR, 1 to 2 days) and enrolled a median of 329 patients (IQR, 199 to 456 patients). Although all but 1 of the 48 approved NDAs were for previously approved moieties, analysis of available NDAs for referent products yielded similar findings.
Limitations
The analysis was limited to approved opioids. Animal studies and nonpivotal trials were excluded. Evidence for safety in NDAs was presented for chronic pain only.
Conclusion
Between 1997 and 2018, the FDA approved opioids on the basis of pivotal trials of short or intermediate duration, often in narrowly defined pain populations of patients who could tolerate the drug. Systematic collation of certain important safety outcomes was rare.
Primary funding source
None.



Ann Intern Med: 28 Sep 2020; epub ahead of print
Heyward J, Moore TJ, Chen J, Meek K, Lurie P, Alexander GC
Ann Intern Med: 28 Sep 2020; epub ahead of print | PMID: 32986486
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Impact:
Abstract

Physical Therapy Referral From Primary Care for Acute Back Pain With Sciatica : A Randomized Controlled Trial.

Fritz JM, Lane E, McFadden M, Brennan G, ... Meier W, Greene T
Background
Few studies have examined primary care management for acute sciatica, including referral to physical therapy.
Objective
To evaluate whether early referral to physical therapy reduced disability more than usual care (UC) alone for patients with acute sciatica.
Design
Randomized controlled clinical trial. (ClinicalTrials.gov: NCT02391350).
Setting
2 health care systems in Salt Lake City, Utah.
Patients
220 adults aged 18 to 60 years with sciatica of less than 90 days\' duration who were making an initial primary care consultation.
Intervention
All participants received imaging and medication at the discretion of the primary care provider before enrollment. A total of 110 participants randomly assigned to UC were provided 1 session of education, and 110 participants randomly assigned to early physical therapy (EPT) were provided 1 education session and then referred for 4 weeks of physical therapy, including exercise and manual therapy.
Measurements
The primary outcome was the Oswestry Disability Index (OSW) score after 6 months. Secondary outcomes were pain intensity, patient-reported treatment success, health care use, and missed workdays.
Results
Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, -5.4 points [95% CI, -9.4 to -1.3 points];= 0.009). The OSW and several secondary outcomes favored EPT after 4 weeks. After 1 year, between-group differences favored EPT for the OSW (relative difference, -4.8 points [CI, -8.9 to -0.7 points]) and back pain intensity (relative difference, -1.0 points [CI, -1.6 to -0.4 points]). The EPT group was more likely to self-report treatment success after 1 year (45.2%) than the UC group (27.6%) (relative risk, 1.6 [CI, 1.1 to 2.4]). There were no significant differences in health care use or missed workdays.
Limitation
The patients and providers were unblinded, and specific physical therapy interventions responsible for effects could not be determined.
Conclusion
Referral from primary care to physical therapy for recent-onset sciatica improved disability and other outcomes compared with UC.
Primary funding source
Agency for Healthcare Research and Quality.



Ann Intern Med: 05 Oct 2020; epub ahead of print
Fritz JM, Lane E, McFadden M, Brennan G, ... Meier W, Greene T
Ann Intern Med: 05 Oct 2020; epub ahead of print | PMID: 33017565
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Abstract

The Productivity Requirements of Implementing a Medical Scribe Program.

Miksanek TJ, Skandari MR, Ham SA, Lee WW, ... Brown MT, Laiteerapong N
Background
Economic analyses of medical scribes have been limited to individual, specialty-specific clinics.
Objective
To determine the number of additional patient visits various specialties would need to recover the costs of implementing scribes in their practice at 1 year.
Design
Modeling study based on 2015 data from the Centers for Medicare & Medicaid Services (CMS) and National Ambulatory Medical Care Survey. Scribe costs were based on literature review and a third-party contractor model. Revenue was calculated from direct visit billing, CPT (Current Procedural Terminology) billing, and data from the National Ambulatory Medical Care Survey.
Data sources
2015 data from CMS and the National Ambulatory Medical Care Survey.
Target population
Health care providers.
Time horizon
1 year.
Perspective
Office-based clinic.
Outcome measures
The number of additional patient visits a physician must have to recover the costs of a scribe program at 1 year.
Results of base-case analysis
An average of 1.34 additional new patient visits per day (295 per year) were required to recover scribe costs (range, 0.89 [cardiology] to 1.80 [orthopedic surgery] new patient visits per day). For returning patients, an average of 2.15 additional visits per day (472 per year) were required (range, 1.65 [cardiology] to 2.78 [orthopedic surgery] returning visits per day). The addition of 2 new patient (or 3 returning) visits per day was profitable for all specialties.
Results of sensitivity analysis
Results were not sensitive to most inputs, with the exception of hourly scribe cost and inclusion of CPT revenue.
Limitation
Use of Medicare data and failure to account for indirect costs, downstream revenue, or changes in documentation quality.
Conclusion
For all specialties, modest increases in productivity due to scribes may allow physicians to see more patients and offset scribe costs, making scribe programs revenue-neutral.
Primary funding source
University of Chicago Medicine\'s Center for Healthcare Delivery Science and Innovation and the Bucksbaum Institute.



Ann Intern Med: 05 Oct 2020; epub ahead of print
Miksanek TJ, Skandari MR, Ham SA, Lee WW, ... Brown MT, Laiteerapong N
Ann Intern Med: 05 Oct 2020; epub ahead of print | PMID: 33017564
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Abstract

Delirium.

Mattison MLP

Delirium is an acute confusional state that is common and costly and is associated with significant functional decline and distress. It is the manifestation of acute encephalopathy and is variably called , , or . All patients are at risk for delirium, although those with more vulnerabilities (such as advanced age, exposures to other stressors like infection, and certain medications) are at higher risk. The pathophysiologic cause of delirium is not well understood. It is important to recognize patients at risk for and those with delirium and to immediately identify and treat factors contributing to it. There is no single intervention or medication to treat delirium, making it challenging to manage. Therefore, risk mitigation and prompt treatment rely on a sophisticated strategy to address the contributing factors. Delirium may be prevented or attenuated when multimodal strategies are used, thereby improving patient outcomes.



Ann Intern Med: 05 Oct 2020; 173:ITC49-ITC64
Mattison MLP
Ann Intern Med: 05 Oct 2020; 173:ITC49-ITC64 | PMID: 33017552
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Abstract

Should You Recommend Direct-to-Consumer Genetic Testing for This Patient? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Smetana GW, Vassy JL, Hofstatter E, Libman H

In recent years, the number of patients choosing to have direct-to-consumer (DTC) genetic testing without involving their clinicians has increased substantially. For example, the number of subscribers to a commonly used testing site has grown to more than 10 million. These services have been heavily marketed in the United States and often include information about ancestry; genetic traits; and, increasingly, disease risk. In clinical care, genetic testing by a physician is accompanied by both pre- and posttest counseling by a trained genetic counselor. However, there are not enough genetic counselors to meet the needs of all persons contemplating DTC genetic testing. Formal genetic counseling includes preparation of a family pedigree; a discussion about potential benefits, the possibility that some information might be stressful to receive or difficult to understand, and the potential for disclosure of genetic information; and a detailed informed consent process. Some DTC tests for genetic susceptibilities look for only a few known mutations in a particular gene (such as ); a negative test result does not exclude the possibility of a clinically important mutation. A positive DTC genetic test result that might change clinical management should be followed by a confirmatory test through a genetics laboratory. Here, 2 expert physicians-a general internist and a medical oncologist with genetics experience-discuss an approach to counseling a patient who is considering DTC testing to learn more about his ancestry and his risk for metabolic syndrome.



Ann Intern Med: 05 Oct 2020; 173:563-571
Smetana GW, Vassy JL, Hofstatter E, Libman H
Ann Intern Med: 05 Oct 2020; 173:563-571 | PMID: 33017547
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Abstract

Remdesivir for Adults With COVID-19 : A Living Systematic Review for an American College of Physicians Practice Points.

Wilt TJ, Kaka AS, MacDonald R, Greer N, Obley A, Duan-Porter W
Background
Few treatments exist for coronavirus disease 2019 (COVID-19).
Purpose
To evaluate the effectiveness and harms of remdesivir for COVID-19.
Data sources
Several databases, tables of contents of journals, and U.S. Food and Drug Administration and company websites were searched from 1 January through 31 August 2020.
Study selection
English-language, randomized trials of remdesivir treatments for adults with suspected or confirmed COVID-19. New evidence will be incorporated using living review methods.
Data extraction
Single-reviewer abstraction and risk-of-bias assessment verified by a second reviewer; GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods used for certainty-of-evidence assessments.
Data synthesis
Four randomized trials were included. In adults with severe COVID-19, remdesivir compared with placebo probably improves recovery by a large amount (absolute risk difference [ARD] range, 7% to 10%) and may result in a small reduction in mortality (ARD range, -4% to 1%) and a shorter time to recovery or clinical improvement. Remdesivir may have little to no effect on hospital length of stay. Remdesivir probably reduces serious adverse events by a moderate amount (ARD range, -6% to -8%). Compared with a 10-day remdesivir course, a 5-day course may reduce mortality, increase recovery or clinical improvement by small to moderate amounts, reduce time to recovery, and reduce serious adverse events among hospitalized patients not requiring mechanical ventilation. Recovery due to remdesivir may not vary by age, sex, symptom duration, or disease severity.
Limitations
Low-certainty evidence with few published trials, including 1 preliminary report and 2 open-label trials. Trials excluded pregnant women and adults with severe kidney or liver disease.
Conclusion
In hospitalized adults with COVID-19, remdesivir probably improves recovery and reduces serious adverse events and may reduce mortality and time to clinical improvement. For adults not receiving mechanical ventilation or extracorporeal membrane oxygenation, a 5-day course of remdesivir may provide similar benefits to and fewer harms than a 10-day course.
Primary funding source
U.S. Department of Veterans Affairs, Veterans Health Administration Office of Research and Development, Health Services Research and Development Service, and Evidence Synthesis Program.



Ann Intern Med: 04 Oct 2020; epub ahead of print
Wilt TJ, Kaka AS, MacDonald R, Greer N, Obley A, Duan-Porter W
Ann Intern Med: 04 Oct 2020; epub ahead of print | PMID: 33017170
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Impact:
Abstract

Evaluation of Hospital Performance Using the Excess Days in Acute Care Measure in the Hospital Readmissions Reduction Program.

Wadhera RK, Maddox KEJ, Desai NR, Landon BE, ... Shen C, Yeh RW

The Hospital Readmissions Reduction Program (HRRP) has penalized hospitals with higher 30-day readmission rates more than $3 billion to date. Clinicians and policy experts have raised concerns that the 30-day readmission measure used in this program provides an incomplete picture of performance because it does not capture all hospital encounters that may occur after discharge. In contrast, the excess days in acute care (EDAC) measure, which currently is not used in the HRRP, captures the full spectrum of hospital encounters (emergency department, observation stay, inpatient readmission) and their associated lengths of stay within 30 days of discharge. This study of 3173 hospitals that participated in the HRRP in fiscal year 2019 compared performance on the readmission and EDAC measures and evaluated whether using the EDAC measure would change hospitals\' penalty status for 3 conditions targeted by the HRRP. Overall, only moderate agreement was found on hospital performance rankings by using the readmission and EDAC measures (weighted κ statistic: heart failure, 0.45 [95% CI, 0.42 to 0.47]; acute myocardial infarction [AMI], 0.37 [CI, 0.35 to 0.40]; and pneumonia, 0.50 [CI, 0.47 to 0.52]). Under the HRRP, the penalty status of 769 (27.0%) of 2845 hospitals for heart failure, 581 (28.3%) of 2055 for AMI, and 724 (24.9%) of 2911 for pneumonia would change if the EDAC measure were used instead of the readmission measure to evaluate performance. Fewer small and rural hospitals would receive penalties. The Centers for Medicare & Medicaid Services should consider using the EDAC measure, which provides a more comprehensive picture of postdischarge hospital use, rather than the 30-day readmission measure to evaluate health care system performance under federal quality, reporting, and value-based programs.



Ann Intern Med: 12 Oct 2020; epub ahead of print
Wadhera RK, Maddox KEJ, Desai NR, Landon BE, ... Shen C, Yeh RW
Ann Intern Med: 12 Oct 2020; epub ahead of print | PMID: 33045180
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Abstract

How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan.

Cheng SY, Wang CJ, Shen AC, Chang SC

Reopening colleges and universities during the coronavirus disease 2019 (COVID-19) pandemic poses a special challenge worldwide. Taiwan is one of the few countries where schools are functioning normally. To secure the safety of students and staff, the Ministry of Education in Taiwan established general guidelines for college campuses. The guidelines delineated creation of a task force at each university; school-based risk screening based on travel history, occupation, contacts, and clusters; measures on self-management of health and quarantine; general hygiene measures (including wearing masks indoors); principles on ventilation and sanitization; regulations on school assemblies; a process for reporting suspected cases; and policies on school closing and make-up classes. It also announced that a class should be suspended if 1 student or staff member in it tested positive and that a school should be closed for 14 days if it had 2 or more confirmed cases. As of 18 June 2020, there have been 7 confirmed cases in 6 Taiwanese universities since the start of the pandemic. One university was temporarily closed, adopted virtual classes, and quickly reopened after 14 days of contact tracing and quarantine of possible contacts. Taiwan\'s experience suggests that, under certain circumstances, safely reopening colleges and universities this fall may be feasible with a combination of strategies that include containment (access control with contact tracing and quarantine) and mitigation (hygiene, sanitation, ventilation, and social distancing) practices.



Ann Intern Med: 19 Oct 2020; 173:638-641
Cheng SY, Wang CJ, Shen AC, Chang SC
Ann Intern Med: 19 Oct 2020; 173:638-641 | PMID: 32614638
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Abstract

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.

Skipper CP, Pastick KA, Engen NW, Bangdiwala AS, ... Rajasingham R, Boulware DR
Background
No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).
Objective
To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.
Design
Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).
Setting
Internet-based trial across the United States and Canada (40 states and 3 provinces).
Participants
Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.
Intervention
Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.
Measurements
Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.
Results
Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point];  = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo ( = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo ( < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death ( = 0.29).
Limitation
Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.
Conclusion
Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.
Primary funding source
Private donors.



Ann Intern Med: 19 Oct 2020; 173:623-631
Skipper CP, Pastick KA, Engen NW, Bangdiwala AS, ... Rajasingham R, Boulware DR
Ann Intern Med: 19 Oct 2020; 173:623-631 | PMID: 32673060
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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

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:

This program is still in alpha version.