Royal Australian College of General Practitioners



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MEDICAL JOURNALS – DECEMBER 2020

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Annals of Internal Medicine Vol. 173 No. 8 October 20 2020

Qaseem A, Etxeandia-Ikobaltzeta I, Yost J, et al.

Use of N95, Surgical, and Cloth Masks to Prevent COVID-19 in Health Care and Community Settings: Living Practice Points From the American College of Physicians (Version 1).

pp642-649. doi:10.7326/M20-3234. PMID: 32551813; PMCID: PMC7357230.

Controversy exists around the appropriate types of masks and the situations in which they should be used in community and health care settings for the prevention of SARS-CoV-2 infection. In this article, the American College of Physicians (ACP) provides recommendations based on the best available evidence through 14 April 2020 on the effectiveness of N95 respirators, surgical masks, and cloth masks in reducing transmission of infection. The ACP plans periodic updates of these recommendations on the basis of ongoing surveillance of the literature for 1 year from the initial search date.

Skipper CP, Pastick KA, Engen NW, et al.

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

pp623-631. doi:10.7326/M20-4207. PMID: 32673060; PMCID: PMC7384270.

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. 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]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 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 (P = 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.

Cheng SY, Wang CJ, Shen AC, et al.

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

pp638-641. doi:10.7326/M20-2927. PMID: 32614638; PMCID: PMC7339040.

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.

Caturegli G, Materi J, Howard BM, et al.

Clinical Validity of Serum Antibodies to SARS-CoV-2 : A Case-Control Study.

pp614-622. doi:10.7326/M20-2889. PMID: 32628534; PMCID: PMC7370852.

Background: The clinical utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remains undefined.

Objective: To determine the clinical validity and utility of SARS-CoV-2 antibodies. Design: Case-control study.

Setting: First month of testing for coronavirus disease 2019 (COVID-19) by using a nucleic acid amplification test (NAAT) on nasopharyngeal swabs at the Johns Hopkins Hospital, Baltimore, Maryland (11 066 persons).

Participants: Of the 11 066 tested persons, 115 (1%) were hospitalized adults investigated for COVID-19. Clinical record review was performed to classify them into a COVID-19 case group (n = 60) or a non-COVID-19 control group (n = 55). The laboratory control groups comprised 513 persons not tested by NAAT: 160 healthy laboratory employees, 101 persons positive for IgG antibodies against Epstein-Barr virus capsid antigen, 215 positive for thyroperoxidase antibody, and 37 positive for rheumatoid factor.

Measurements: Serum IgG and IgA antibodies against SARS-CoV-2 spike protein were detected by using enzyme-linked immunosorbent assay.

Results: Sensitivity and specificity of the SARS-CoV-2 IgG assay were 0.976 (95% CI, 0.928 to 0.995) and 0.988 (CI, 0.974 to 0.995), respectively, when performed 14 days or later after symptom onset, but sensitivity decreased at earlier time points. Immunoglobulin G developed rapidly and was sustained at high levels throughout follow-up (up to 58 days). Antibodies to SARS-CoV-2 predicted the odds of developing acute respiratory distress syndrome, which increased by 62% (CI, 48% to 81%; P < 0.001) for every 2-fold increase in IgG. Of 11 066 NAAT-tested patients, 457 were repeatedly NAAT-negative, and serum samples were obtained for 18 such patients (6 COVID-19 case patients and 12 non-COVID-19 control patients). Antibodies were present in 5 of 6 case patients and none of the 12 control patients (P = 0.001).

Limitations: The study was retrospective and performed at a single center; the sample was small; follow-up was limited; and selection bias may have occurred.

Conclusion: Antibodies to SARS-CoV-2 demonstrate infection when measured at least 14 days after symptom onset, are associated with clinical severity, and provide valuable diagnostic support in patients who test negative by NAAT but remain clinically suspicious for COVID-19.

McCaw ZR, Tian L, Vassy JL, et al.

How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19.

pp632-637. doi:10.7326/M20-4044. PMID: 32634024; PMCID: PMC7350552.

Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan-Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.

Lechien JR, Chiesa-Estomba CM, Hans S, et al.

Loss of Smell and Taste in 2013 European Patients With Mild to Moderate COVID-19.

pp672-675. doi:10.7326/M20-2428. PMID: 32449883; PMCID: PMC7505100.

Doyle TJ.

COVID-19, Prison Visits, and the Value of a Cup of Coffee.

pp666-667. doi:10.7326/M20-3073. PMID: 32479164.

Chow EJ, Rolfes MA, O'Halloran A, et al.

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

pp605-613. doi:10.7326/M20-1509. PMID: 32833488.

Schluger NW.

The Saga of Hydroxychloroquine and COVID-19: A Cautionary Tale.

pp662-663. doi:10.7326/M20-5041. PMID: 32673059; PMCID: PMC7384271.

Tanael M.

Point-of-Care Ultrasonography, Primary Care, and Prudence.

pp650-651. doi:10.7326/M20-1840. PMID: 32687742.

Ludvigsson JF, Winell H, Sandin S, et al.

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

pp597-604. doi:10.7326/M20-0167. PMID: 32866418.

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.

Schoergenhofer C, Jilma B, Stimpfl T, et al.

Pharmacokinetics of Lopinavir and Ritonavir in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19).

pp670-672. doi:10.7326/M20-1550. PMID: 32422065; PMCID: PMC7236891.

Rousseau P.

Immigrant COVID.

p667. doi:10.7326/M20-4732. PMID: 32744866.

Prioleau P.

After the Night Shift.

p684. doi:10.7326/M19-1177. PMID: 33075269.

Wrighton MS, Lawrence SJ.

Reopening Colleges and Universities During the COVID-19 Pandemic.

pp664-665. doi:10.7326/M20-4752. PMID: 32614640; PMCID: PMC7339038.

Tigges S, Ward PJ.

Annals Graphic Medicine - How the Virus Stole Anatomy.

W135-W142. doi:10.7326/G20-0048. PMID: 32614641.

Addis A, Genazzani A, Trotta MP, et al.

Promoting Better Clinical Trials and Drug Information as Public Health Interventions for the COVID-19 Emergency in Italy.

pp654-655. doi:10.7326/M20-3775. PMID: 32543882; PMCID: PMC7322772.

Sacks HS.

Accuracy of point-of-care diagnostic tests for SARS-CoV-2 antibodies (IgM/IgG) is heterogeneous.

JC47. doi:10.7326/ACPJ202010200-047. PMID: 33075255.

Centor RM, Brown JM.

Web Exclusive. Annals On Call - Underdiagnosis of Primary Aldosteronism.

OC1. doi:10.7326/A19-0040. PMID: 33075251.

Piaditis GP, Kaltsas G, Markou A, et al.

The Unrecognized Prevalence of Primary Aldosteronism.

p681. doi:10.7326/L20-1096. PMID: 33075252.

Vaidya A, Brown JM, Carey RM, et al.

The Unrecognized Prevalence of Primary Aldosteronism.

p683. doi:10.7326/L20-1097. PMID: 33075250.

Sosa Barrios RH, Menacho-Román M, Mataix AL, et al.

The Unrecognized Prevalence of Primary Aldosteronism.

pp682-683. doi:10.7326/L20-1095. PMID: 33075253.

Pilz S, Grübler MR, Theiler-Schwetz V, et al.

The Unrecognized Prevalence of Primary Aldosteronism.

pp681-682. doi:10.7326/L20-1094. PMID: 33075254.

Chou R, Dana T, Buckley DI, et al.

Update Alert 4: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers.

pp143-144. doi:10.7326/L20-1134. PMID: 32915642; PMCID: PMC7505020.

Stone VE.

White Coats for Black Lives: The Time Has Come for Action.

pp656-657. doi:10.7326/M20-4280. PMID: 32551811.

Tuite AR, Greer AL, De Keninck S, et al.

Risk for COVID-19 Resurgence Related to Duration and Effectiveness of Physical Distancing in Ontario, Canada.

pp675-678. doi:10.7326/M20-2945. PMID: 32459528; PMCID: PMC7277487.

Griffin TP, Dinneen SF.

SGLT2 inhibitors increase risk for diabetic ketoacidosis in type 2 diabetes.

JC40. doi:10.7326/ACPJ202010200-040. PMID: 33075260.

Kimmel SE, Califf RM, Dean NE, et al.

COVID-19 Clinical Trials: A Teachable Moment for Improving Our Research Infrastructure and Relevance. pp652-653. doi:10.7326/M20-2959. PMID: 32543881; PMCID: PMC7322771.

Trowbridge RL, Rencic JJ, Wijesekera TP, et al.

Avoiding Cognitive Errors in Clinical Decision Making.

pp678-679. doi:10.7326/L20-1059. PMID: 33075248.

Laine C.

Annals for Educators - 20 October 2020.

ED8. doi:10.7326/AWED202010200. PMID: 33075273.

Restrepo D, Armstrong KA, Metlay JP.

Avoiding Cognitive Errors in Clinical Decision Making.

p679. doi:10.7326/L20-1060. PMID: 33075247.

Musher DM.

Avoiding Cognitive Errors in Clinical Decision Making.

p679. doi:10.7326/L20-1058. PMID: 33075249.

Jacobs ZG.

Web Exclusive. Annals Graphic Medicine - Hats.

W133-W134. doi:10.7326/G20-0012. PMID: 33075256.

DePew R.

Memory Care Unit.

p637. doi:10.7326/M19-2736. PMID: 33075265.

Nanna MG, Granger CB.

In ACS, ticagrelor and prasugrel each reduce some ischemic events but increase major bleeding vs. clopidogrel.

JC44. doi:10.7326/ACPJ202010200-044. PMID: 33075264.

Bavishi C.

In ACS treated with drug-eluting stents and 3 mo of DAPT, ticagrelor monotherapy reduced clinical events at

1 y vs. DAPT.

JC43. doi:10.7326/ACPJ202010200-043. PMID: 33075261.

Wesorick DH, Chopra V.

Annals for Hospitalists - 20 October 2020.

ED8. doi:10.7326/AWHO202010200. PMID: 33075266.

Horton LC, Feuerstein JD.

In adults with severe acute GI bleeding, tranexamic acid did not reduce death due to bleeding at 5 days.

JC46. doi:10.7326/ACPJ202010200-046. PMID: 33075257.

MacIntyre CR.

Influenza Vaccine: Routine Secondary Prevention for Patients With Cardiovascular Disease?

pp660-661. doi:10.7326/M20-5810. PMID: 32833491.

Stern RH.

Locally Informed Simulation to Predict Hospital Capacity Needs During the COVID-19 Pandemic.

pp679-680. doi:10.7326/L20-1061. PMID: 33075246.

Weissman GE, Crane-Droesch A, Chivers C, et al.

Locally Informed Simulation to Predict Hospital Capacity Needs During the COVID-19 Pandemic.

pp680-681. doi:10.7326/L20-1062. PMID: 33075245.

Nightingale TE, Tejpar T, O'Connell C, et al.

Using Cannabis to Control Blood Pressure After Spinal Cord Injury: A Case Report.

pp668-670. doi:10.7326/L20-0090. PMID: 32539443.

Holbrook AM.

USPSTF recommends asking adults screening questions about unhealthy drug use.

JC38. doi:10.7326/ACPJ202010200-038. PMID: 33075271.

Merli GJ, Weitz HH.

Web Exclusive. Annals Consult Guys – Preoperative Cannabis: Reason to Postpone Surgery?

CG1. doi:10.7326/W19-0043. PMID: 33075267.

Haley SP, Chessman A.

Treatment effect of aspirin for primary prevention does not differ according to baseline ASCVD risk.

JC39. doi:10.7326/ACPJ202010200-039. PMID: 33075272.

Singh A, Sonpar A.

In adults exposed to COVID-19, hydroxychloroquine did not reduce confirmed or probable COVID-19; trial stopped for futility.

JC41. doi:10.7326/ACPJ202010200-041. PMID: 33075259.

Alvarado F, Borzak S.

After PCI and short-term DAPT, P2Y12 inhibitors alone vs. ongoing DAPT reduce major bleeding; CV events do not differ.

JC42. doi:10.7326/ACPJ202010200-042. PMID: 33075262.

Davenport MS, Weinreb JC.

Web Exclusive. Annals for Hospitalists Inpatient Notes - What Hospitalists Need to Know About Risk for Contrast-Induced Acute Kidney Injury From Contrast-Enhanced Computed Tomography.

HO2-HO3. doi:10.7326/M20-6296. PMID: 33075258.

Hviid A.

Vaccine Safety in Pregnancy: Going Beyond the Perinatal Period.

pp658-659. doi:10.7326/M20-5489. PMID: 32866416.

Brophy J.

In adults with chest pain, a troponin limit of detection strategy did not increase early discharge rate.

JC45. doi:10.7326/ACPJ202010200-045. PMID: 33075263.

Annals of Internal Medicine Vol. 173 No. 9 November 3 2020

Qaseem A, McLean RM, O'Gurek D, et al.

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.

pp739-748. doi:10.7326/M19-3602. PMID: 32805126.

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: ACP and AAFP recommend that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with topical nonsteroidal anti-inflammatory drugs (NSAIDs) with or without menthol gel as first-line therapy to reduce or relieve symptoms, including pain; improve physical function; and improve the patient's treatment satisfaction (Grade: strong recommendation; moderate-certainty evidence).

Recommendation 2a: ACP and AAFP suggest that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with oral NSAIDs to reduce or relieve symptoms, including pain, and to improve physical function, or with oral acetaminophen to reduce pain (Grade: conditional recommendation; moderate-certainty evidence).

Recommendation 2b: ACP and AAFP suggest that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with specific acupressure to reduce pain and improve physical function, or with transcutaneous electrical nerve stimulation to reduce pain (Grade: conditional recommendation; low-certainty evidence).

Recommendation 3: ACP and AAFP suggest against clinicians treating patients with acute pain from non-low back, musculoskeletal injuries with opioids, including tramadol (Grade: conditional recommendation; low-certainty evidence).

Busse JW, Sadeghirad B, Oparin Y, et al.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network

Meta-analysis of Randomized Trials.

pp730-738. doi:10.7326/M19-3601. PMID: 32805127.

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.

Sudharsanan N, Didzun O, Bärnighausen T, et al.

The Contribution of the Age Distribution of Cases to COVID-19 Case Fatality Across Countries : A Nine-Country Demographic Study.

pp714-720. doi:10.7326/M20-2973. PMID: 32698605; PMCID: PMC7397549.

Background: There is wide variation in coronavirus disease 2019 (COVID-19) case-fatality rates (CFRs) across countries, leading to uncertainty about the true lethality of the disease. A large part of this variation may be due to the ages of individuals who are tested and identified.

Objective: To measure the contribution of distortions from the age distributions of confirmed cases to CFRs within and across populations.

Design: Cross-sectional demographic study using aggregate data on COVID-19 cases and deaths by age.

Setting: Population-based data from China, France, Germany, Italy, the Netherlands, South Korea, Spain, Switzerland, and the United States.

Participants: All individuals with confirmed COVID-19, as reported by each country as of 19 April 2020

(n = 1 223 261).

Measurements: Age-specific COVID-19 CFRs and age-specific population shares by country.

Results: The overall observed CFR varies widely, with the highest rates in Italy (9.3%) and the Netherlands (7.4%) and the lowest rates in South Korea (1.6%) and Germany (0.7%). Adjustment for the age distribution of cases explains 66% of the variation across countries, with a resulting age-standardized median CFR of 1.9%. Among a larger sample of 95 countries, the observed variation in COVID-19 CFRs is 13 times larger than what would be expected on the basis of just differences in the age composition of countries.

Limitation: The age-adjusted rates assume that, conditional on age, COVID-19 mortality among diagnosed cases is the same as that among undiagnosed cases and that individuals of all ages are equally susceptible to severe acute respiratory syndrome coronavirus 2 infection.

Conclusion: Selective testing and identification of older cases considerably warps estimates of the lethality of COVID-19 within populations and comparisons across countries. Removing age distortions and focusing on differences in age-adjusted case fatality will be essential for accurately comparing countries' performance in caring for patients with COVID-19 and for monitoring the epidemic over time.

Tison GH, Avram R, Kuhar P, et al.

Worldwide Effect of COVID-19 on Physical Activity: A Descriptive Study.

pp767-770. doi:10.7326/M20-2665. PMID: 32598162; PMCID: PMC7384265.

Schiavon CA, Bhatt DL, Ikeoka D, et al.

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

pp685-693. doi:10.7326/M19-3781. PMID: 32805133.

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. (: 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/m2 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 ( ................
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