Showing papers in "JAMA Internal Medicine in 2020"

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Abstract: Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

The Mental Health Consequences of COVID-19 and Physical Distancing: The Need for Prevention and Early Intervention.

Abstract: Since the first case of novel coronavirus disease 2019 (COVID-19) was diagnosed in December 2019, it has swept across the world and galvanized global action. This has brought unprecedented efforts to institute the practice of physical distancing (called in most cases “social distancing”) in countries all over the world, resulting in changes in national behavioral patterns and shutdowns of usual day-to-day functioning. While these steps may be critical to mitigate the spread of this disease, they will undoubtedly have consequences for mental health and well-being in both the short and long term. These consequences are of sufficient importance that immediate efforts focused on prevention and direct intervention are needed to address the impact of the outbreak on individual and population level mental health. The sparse literature on the mental health consequences of epidemics relates more to the sequelae of the disease itself (eg, mothers of children with congenital Zika syndrome) than to social distancing. However, largescale disasters, whether traumatic (eg, the World Trade Center attacks or mass shootings), natural (eg, hurricanes), or environmental (eg, Deepwater Horizon oil spill), are almost always accompanied by increases in depression, posttraumatic stress disorder (PTSD), substance use disorder, a broad range of other mental and behavioral disorders, domestic violence, and child abuse.1 For example, 5% of the population affected by Hurricane Ike in 2008 met the criteria for major depressive disorder in the month after the hurricane; 1 out of 10 adults in New York City showed signs of the disorder in the month following the 9/11 attacks.2,3 And almost 25% of New Yorkers reported increased alcohol use after the attacks.4 Communities affected by the Deepwater Horizon oil spill showed signs of clinically significant depression and anxiety.5 The SARS epidemic was also associated with increases in PTSD, stress, and psychological distress in patients and clinicians.6 For such events, the impact on mental health can occur in the immediate aftermath and then persist over long time periods. In the context of the COVID-19 pandemic, it appears likely that there will be substantial increases in anxiety and depression, substance use, loneliness, and domestic violence; and with schools closed, there is a very real possibility of an epidemic of child abuse. This concern is so significant that the UK has issued psychological first aid guidance from Mental Health UK.7 While the literature is not clear about the science of population level prevention, it leads us to conclude that 3 steps, taken now, can help us proactively prepare for the inevitable increase in mental health conditions and associated sequelae that are the consequences of this pandemic. First, it is necessary to plan for the inevitability of loneliness and its sequelae as populations physically and socially isolate and to develop ways to intervene. The use of digital technologies can bridge social distance, even while physical distancing measures are in place.8 Normal structures where people congregate, whether places of worship, or gyms, and yoga studios, can conduct online activities on a schedule similar to what was in place prior to social distancing. Some workplaces are creating virtual workspace where people can work and connect over video connections, so they are not virtually alone. Employers should ensure that each employee receives daily outreach during the work week, through a supervisor or buddy system, just to maintain social contact. Many observers note that outreach that involves voice and/or video is superior to email and text messaging. Extra efforts should be made to ensure connections with people who are typically marginalized and isolated, including the elderly, undocumented immigrants, homeless persons and those with mental illness. Social media can also be used to encourage groups to connect and direct individuals to trusted resources for mental health support. These platforms can also enhance check-in functions to provide regular contact with individuals as well as to allow people to share with others information about their well-being and resource needs. Even with all of these measures, there will still be segments of the population that are lonely and isolated. This suggests the need for remote approaches for outreach and screening for loneliness and associated mental health conditions so that social support can be provided. Particularly relevant here is the developing and implementing routines, particularly for children who are out of school, ensuring that they have access to regular programmed work. Online substitutes for daily routines, as mentioned above, can be extremely helpful, but not all children have access to technologies that enable remote connectivity. Needed are approaches for ensuring structure, continuity of learning, and socialization to mitigate the effect of shortand long-term sheltering in place. Second, it is critical that we have in place mechanisms for surveillance, reporting, and intervention, particularly, when it comes to domestic violence and child abuse. Individuals at risk for abuse may have limited opportunities to report or seek help when shelter-in-place requirements demand prolonged cohabitation at home and limit travel outside of the home. Systems will need to balance the need for social distancing with the availability of safe places to VIEWPOINT

Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy

Abstract: Importance Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). Objective To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. Design, Setting, and Participants This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase–polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. Exposures Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. Main Outcomes and Measures Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. Results Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). Conclusions and Relevance In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.

Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19.

Abstract: Importance Early identification of patients with novel coronavirus disease 2019 (COVID-19) who may develop critical illness is of great importance and may aid in delivering proper treatment and optimizing use of resources. Objective To develop and validate a clinical score at hospital admission for predicting which patients with COVID-19 will develop critical illness based on a nationwide cohort in China. Design, Setting, and Participants Collaborating with the National Health Commission of China, we established a retrospective cohort of patients with COVID-19 from 575 hospitals in 31 provincial administrative regions as of January 31, 2020. Epidemiological, clinical, laboratory, and imaging variables ascertained at hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-GRAM). The score provides an estimate of the risk that a hospitalized patient with COVID-19 will develop critical illness. Accuracy of the score was measured by the area under the receiver operating characteristic curve (AUC). Data from 4 additional cohorts in China hospitalized with COVID-19 were used to validate the score. Data were analyzed between February 20, 2020 and March 17, 2020. Main Outcomes and Measures Among patients with COVID-19 admitted to the hospital, critical illness was defined as the composite measure of admission to the intensive care unit, invasive ventilation, or death. Results The development cohort included 1590 patients. the mean (SD) age of patients in the cohort was 48.9 (15.7) years; 904 (57.3%) were men. The validation cohort included 710 patients with a mean (SD) age of 48.2 (15.2) years, and 382 (53.8%) were men and 172 (24.2%). From 72 potential predictors, 10 variables were independent predictive factors and were included in the risk score: chest radiographic abnormality (OR, 3.39; 95% CI, 2.14-5.38), age (OR, 1.03; 95% CI, 1.01-1.05), hemoptysis (OR, 4.53; 95% CI, 1.36-15.15), dyspnea (OR, 1.88; 95% CI, 1.18-3.01), unconsciousness (OR, 4.71; 95% CI, 1.39-15.98), number of comorbidities (OR, 1.60; 95% CI, 1.27-2.00), cancer history (OR, 4.07; 95% CI, 1.23-13.43), neutrophil-to-lymphocyte ratio (OR, 1.06; 95% CI, 1.02-1.10), lactate dehydrogenase (OR, 1.002; 95% CI, 1.001-1.004) and direct bilirubin (OR, 1.15; 95% CI, 1.06-1.24). The mean AUC in the development cohort was 0.88 (95% CI, 0.85-0.91) and the AUC in the validation cohort was 0.88 (95% CI, 0.84-0.93). The score has been translated into an online risk calculator that is freely available to the public (http://118.126.104.170/) Conclusions and Relevance In this study, a risk score based on characteristics of COVID-19 patients at the time of admission to the hospital was developed that may help predict a patient’s risk of developing critical illness.

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset.

Abstract: Importance The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. Objective To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. Design, Setting, and Participants This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. Main Outcomes and Measures Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). Results We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 44 men and 56 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). Conclusions and Relevance In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.

Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

Abstract: Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020.

Abstract: Importance Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US. Design, Setting, and Participants This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State. Exposures Infection with SARS-CoV-2. Main Outcomes and Measures The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date. Results Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases. Conclusions and Relevance During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

Is a "Cytokine Storm" Relevant to COVID-19?

Abstract: In its most severe form, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), leads to a life-threatening pneumonia and acute respiratory distress syndrome (ARDS). The mortality rate from COVID-19 ARDS can approach 40% to 50%.1,2 Although the mechanisms of COVID-19–induced lung injury are still being elucidated, the term cytokine storm has become synonymous with its pathophysiology, both in scientific publications and the media. Absent convincing data of their effectiveness in COVID-19, drugs such as tocilizumab and sarilumab, which are monoclonal antibodies targeting interleukin (IL)-6 activity, are being used to treat patients; trials of these agents typically cite the cytokine storm as their rationale (NCT04306705, NCT04322773). A critical evaluation of the term cytokine storm and its relevance to COVID-19 is warranted. Cytokine storm has no definition. Broadly speaking, it denotes a hyperactive immune response characterized by the release of interferons, interleukins, tumor-necrosis factors, chemokines, and several other mediators. These mediators are part of a well-conserved innate immune response necessary for efficient clearance of infectious agents. Cytokine storm implies that the levels of released cytokines are injurious to host cells. Distinguishing an appropriate from a dysregulated inflammatory response in the pathophysiology of critical illness, however, has been a major challenge. To add further complexity, most mediators implicated in cytokine storm demonstrate pleotropic downstream effects and are frequently interdependent in their biological activity. The interactions of these mediators and the pathways they inform are neither linear nor uniform. Further, although their quantified levels may suggest severity of responses, they do not necessarily imply pathogenesis. This complex interplay illustrates the limitations of interfering in the acute inflammatory response based on single mediators and at indiscriminate time points. Whyhasthe“cytokinestorm”beensocloselyassociatedwith COVID-19? During the SARS epidemic caused by SARS-CoV-1, the termcytokinestormwasdescribedasafeatureandassociatedwith adverseoutcomes.3 SeveralearlycaseseriesinCOVID-19reported levelsofsomeplasmacytokineselevatedabovethenormalrange. In most cases, however, they are lower than plasma levels in previous cohorts of patients with ARDS. Interleukin-6, a proinflammatory cytokine, is a key mediator in the acute inflammatory response and the purported cytokine storm. The Table summarizes reported IL-6 levels in 5 cohorts of patients with COVID-19,1,2,4-6 each with more than 100 patients, and 3 cohorts of patients with ARDS.7-9 Although the median values are above the normal range in many (but not all) cases, they are lower than the median values typically reported in ARDS. The median values in random-

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea.

Abstract: Importance There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. Design, Setting, and Participants A retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea. Main Outcomes and Measures Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care personnel carefully identified patients’ symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription–polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients. Results Of the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients (P = .07). The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients (β = −0.065 [SE, 0.023];P = .005). Conclusions and Relevance In this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2.

Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020.

Abstract: Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19–reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

Assessing Telemedicine Unreadiness Among Older Adults in the United States During the COVID-19 Pandemic.

Abstract: This cross-sectional study uses 2018 data from the National Health and Aging Trends Study to assess the prevalence among older adults in the United States of unreadiness to access video or telephone telemedicine because of disability or inexperience with technology.

Trends in Mortality for Medicare Beneficiaries Treated in the Emergency Department From 2009 to 2016.

Abstract: Importance Emergency department (ED) visits are common and increasing. Whether outcomes associated with care in the ED are improving over time is largely unknown to date. Objective To examine trends in 30-day mortality rates associated with ED care among Medicare beneficiaries aged 65 years or older. Design, Setting, and Participants This cross-sectional study used a random 5% sample in 2009 and 2010 and a 20% sample from 2011 to 2016, for a total of 15 416 385 ED visits from 2009 to 2016 among Medicare beneficiaries aged 65 years or older. Exposures Time (year) as a continuous variable. Main Outcomes and Measures The primary outcome was 30-day mortality, overall and stratified by illness severity and hospital characteristics. Secondary outcomes included mortality rates on the day of the ED visit (day 0) as well as at 7 and 14 days. Changes in disposition from the ED (admission, observation, transfer, died in the ED, and discharged) over time were also examined. Results The sample included 15 416 385 ED visits (60.8% women and 39.2% men; mean [SD] age, 78.6 [8.5] years) at 4828 acute care hospitals. The percentage of patients discharged from the ED increased from 53.6% in 2009 to 56.7% in 2016. Unadjusted 30-day mortality declined from 5.1% in 2009 to 4.6% in 2016 (−0.068% per year; 95% CI, −0.074% to −0.063% per year;P Conclusions and Relevance Among Medicare beneficiaries receiving ED care in the United States, mortality within 30 days of an ED visit appears to have declined in recent years, particularly for patients with the highest severity of illness, even as fewer patients are being admitted from an ED visit. This study’s findings suggest that further study is needed to understand the reasons for this decline and why certain types of hospitals are seeing greater improvements in outcomes.

Trends in Emergency Department Visits and Hospital Admissions in Health Care Systems in 5 States in the First Months of the COVID-19 Pandemic in the US.

Abstract: Importance As coronavirus disease 2019 (COVID-19) spread throughout the US in the early months of 2020, acute care delivery changed to accommodate an influx of patients with a highly contagious infection about which little was known. Objective To examine trends in emergency department (ED) visits and visits that led to hospitalizations covering a 4-month period leading up to and during the COVID-19 outbreak in the US. Design, Setting, and Participants This retrospective, observational, cross-sectional study of 24 EDs in 5 large health care systems in Colorado (n = 4), Connecticut (n = 5), Massachusetts (n = 5), New York (n = 5), and North Carolina (n = 5) examined daily ED visit and hospital admission rates from January 1 to April 30, 2020, in relation to national and the 5 states’ COVID-19 case counts. Exposures Time (day) as a continuous variable. Main Outcomes and Measures Daily counts of ED visits, hospital admissions, and COVID-19 cases. Results A total of 24 EDs were studied. The annual ED volume before the COVID-19 pandemic ranged from 13 000 to 115 000 visits per year; the decrease in ED visits ranged from 41.5% in Colorado to 63.5% in New York. The weeks with the most rapid rates of decrease in visits were in March 2020, which corresponded with national public health messaging about COVID-19. Hospital admission rates from the ED were stable until new COVID-19 case rates began to increase locally; the largest relative increase in admission rates was 149.0% in New York, followed by 51.7% in Massachusetts, 36.2% in Connecticut, 29.4% in Colorado, and 22.0% in North Carolina. Conclusions and Relevance From January through April 2020, as the COVID-19 pandemic intensified in the US, temporal associations were observed with a decrease in ED visits and an increase in hospital admission rates in 5 health care systems in 5 states. These findings suggest that practitioners and public health officials should emphasize the importance of visiting the ED during the COVID-19 pandemic for serious symptoms, illnesses, and injuries that cannot be managed in other settings.

Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China.

Abstract: Importance Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

What Other Countries Can Learn From Italy During the COVID-19 Pandemic.

Abstract: In the coronavirus disease 2019 (COVID-19) pandemic, Italy has been hit very hard,1 with 110 574 documented cases and 13 155 documented deaths related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as of April 1, 2020. The number of cases and deaths cannot be explained simply because of the epidemic starting in Italy earlier compared with other countries besides China. It is important to understand why death rates were so high in Italy to learn how to best prepare and how to plan for optimal actions in other countries. Some contributing factors may be immutable (eg, age structure of the population), but even these need to be laid out carefully in preparedness assessments. Some other contributing factors are potentially modifiable. Some factors pertain to demographics and background disease in the population. Italy has the most elderly population in Europe and the second most elderly population in the world after Japan. COVID-19 has a strong age dependence for the severity of the infection and the risk of death. The median age of people infected with SARS-CoV-2 who are dying in Italy has been 80 years, and the average age of patients requiring critical care support has been 67 years. Moreover, COVID-19 morbidity and mortality is strongly dependent on the presence of concomitant serious diseases, and Italy has a high proportion of patients with history of smoking and high rates of chronic obstructive pulmonary disease and ischemic heart disease.2 The corollary is that preparedness for needs of intensive care unit (ICU) beds and estimates of expected deaths should consider the age structure and chronic diseases of the population served by each health care system. Taking this adjustment into account, burden of disease may be expected to be much less in most areas in the United States, with variability across states and hospital catchment areas. For example, the proportion of the population older than 65 years is 9.5% in Alaska as compared with 19.1% in Florida and 23.1% in Italy. A second set of factors in Italy is the increased burden of cases that presented themselves to the health care system. The proportion of people infected must have been very high in specific areas that were highly affected. In the town of Vò, all 3300 residents were tested the day the first case was detected in the third week of February, and 3% were found to be infected.3 Following aggressive testing, the epidemic was extinguished. However, elsewhere in Italy, it is likely that the prevalence of infection was several times higher in the absence of effective public health intervention. For example, it is likely that the health care system was overwhelmed in Bergamo owing to massive viral transmission during the Champions League match on February 19, 2020 (Atalanta vs Valencia), where a third of the population of Bergamo attended and continued celebrations overnight. Italian life is famous for its socialization and frequent congregations and clustering. It is possible also that in early stages, there was not much adoption of standard hygienic measures, and instructions to stay at home proved difficult to accept, with many complaints registered with the police.4 Accordingly, a higher level of preparedness should be considered for areas where mass gatherings have occurred or where there is extensive social intermingling. A third set of factors pertains to the standard capacity of the health care system and decisions made during hospital management of the presenting cases. Italy has a highly competent state-run health care system, but it has only a modest number of ICU beds and very few subintensive care beds. Overall, 5090 ICU beds (8.4 per 100 000 population) are available in Italy, and 2601 beds in coronary care units (4.3 per 100 000 population),5 as opposed to much higher numbers (36 ICU beds per 100 000 population) in the United States. Given the little experience in dealing with the new virus, it is unavoidable that some strategic mistakes were made about which patients should be hospitalized. In the winter, hospitals tend to run close to full capacity, with 87% average occupancy in Italy during the flu season. Apparently, many patients with relatively modest symptoms were admitted; by the time more patients with severe cases started to arrive, there were limited reserves. Hospital overcrowding may also explain the high infection rate of medical personnel. As of March 30, 2020, 8920 medical personnel had been found to be infected in Italy,6 leading to further loss of capacity for hospitals to respond. Moreover, early infection of medical personnel led to the spread of the infection to other patients within hospitals. In Lombardy, SARS-CoV-2 became largely a nosocomial infection. Nine percent of infections in Italy occurred among health care personnel.6 Characteristically, the first patient with COVID-19 visited the emergency department twice, thus exposing all of the personnel and patients in that area before the infection was recognized. Italy is a decentralized country; thus, preparedness and containment may have been hampered. There was a delay from the first case detection (February 21, 2020) to the first containment decree from the government that closed the relevant villages 3 days later. The lessons relevant to other countries are the need to (1) avoid bringing patients with suspected SARS-CoV-2 infection to the hospital, except when they clearly require hospital care; (2) maintain strict hygienic procedures in the hospital environment; and (3) act swiftly in VIEWPOINT

Assessment of Disparities in Digital Access Among Medicare Beneficiaries and Implications for Telemedicine

Abstract: This cross-sectional study uses data from the 2018 American Community Survey to assess disparities in digital access among Medicare beneficiaries by demographic and socioeconomic characteristics.

Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort

Abstract: Importance Ultraprocessed foods (UPF) are widespread in Western diets. Their consumption has been associated in recent prospective studies with increased risks of all-cause mortality and chronic diseases such as cancer, cardiovascular diseases, hypertension, and dyslipidemia; however, data regarding diabetes is lacking. Objective To assess the associations between consumption of UPF and risk of type 2 diabetes (T2D). Design, Setting, and Participants In this population-based prospective cohort study, 104 707 participants aged 18 years or older from the French NutriNet-Sante cohort (2009-2019) were included. Dietary intake data were collected using repeated 24-hour dietary records (5.7 per participant on average), designed to register participants' usual consumption for more than 3500 different food items. These were categorized according to their degree of processing by the NOVA classification system. Main Outcomes and Measures Associations between UPF consumption and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). Results A total of 104 707 participants (21 800 [20.8%] men and 82 907 [79.2%] women) were included. Mean (SD) baseline age of participants was 42.7 (14.5) years. Absolute T2D rates in the lowest and highest UPF consumers were 113 and 166 per 100 000 person-years, respectively. Consumption of UPF was associated with a higher risk of T2D (multi-adjusted hazard ratio [HR] for an absolute increment of 10 in the percentage of UPF in the diet, 1.15; 95% CI, 1.06-1.25; median follow-up, 6.0 years; 582 252 person-years; 821 incident cases). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet, for other metabolic comorbidities (HR, 1.13; 95% CI, 1.03-1.23), and for weight change (HR, 1.13; 95% CI, 1.01-1.27). The absolute amount of UPF consumption (grams per day) was consistently associated with T2D risk, even when adjusting for unprocessed or minimally processed food intake (HR for a 100 g/d increase, 1.05; 95% CI, 1.02-1.08). Conclusions and Relevance In this large observational prospective study, a higher proportion of UPF in the diet was associated with a higher risk of T2D. Even though these results need to be confirmed in other populations and settings, they provide evidence to support efforts by public health authorities to recommend limiting UPF consumption. Trial Registration ClinicalTrials.gov Identifier:NCT03335644

Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial

Abstract: Importance The efficacy and safety of time-restricted eating have not been explored in large randomized clinical trials. Objective To determine the effect of 16:8-hour time-restricted eating on weight loss and metabolic risk markers. Interventions Participants were randomized such that the consistent meal timing (CMT) group was instructed to eat 3 structured meals per day, and the time-restricted eating (TRE) group was instructed to eatad libitumfrom 12:00pmuntil 8:00pmand completely abstain from caloric intake from 8:00pmuntil 12:00pmthe following day. Design, Setting, and Participants This 12-week randomized clinical trial including men and women aged 18 to 64 years with a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 to 43 was conducted on a custom mobile study application. Participants received a Bluetooth scale. Participants lived anywhere in the United States, with a subset of 50 participants living near San Francisco, California, who underwent in-person testing. Main Outcomes and Measures The primary outcome was weight loss. Secondary outcomes from the in-person cohort included changes in weight, fat mass, lean mass, fasting insulin, fasting glucose, hemoglobin A1clevels, estimated energy intake, total energy expenditure, and resting energy expenditure. Results Overall, 116 participants (mean [SD] age, 46.5 [10.5] years; 70 [60.3%] men) were included in the study. There was a significant decrease in weight in the TRE (−0.94 kg; 95% CI, −1.68 to −0.20;P = .01), but no significant change in the CMT group (−0.68 kg; 95% CI, -1.41 to 0.05,P = .07) or between groups (−0.26 kg; 95% CI, −1.30 to 0.78;P = .63). In the in-person cohort (n = 25 TRE, n = 25 CMT), there was a significant within-group decrease in weight in the TRE group (−1.70 kg; 95% CI, −2.56 to −0.83;P Conclusions and Relevance Time-restricted eating, in the absence of other interventions, is not more effective in weight loss than eating throughout the day. Trial Registration ClinicalTrials.gov Identifiers:NCT03393195andNCT03637855

Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China.

Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied. Objective To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19. Design, Setting, and Participants In this cohort study, a total of 175 patients with mild symptoms of COVID-19 who were hospitalized from January 24 to February 26, 2020, were followed up until March 16, 2020, at Shanghai Public Health Clinical Center, Shanghai, China. Exposures SARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase–polymerase chain reaction testing of nasopharyngeal samples. Main Outcomes and Measures The primary outcome was SARS-CoV-2–specific NAb titers. Secondary outcomes included spike-binding antibodies, cross-reactivity against SARS-associated CoV, kinetics of NAb development, and clinical information, including age, sex, disease duration, length of stay, lymphocyte counts, and blood C-reactive protein level. Results Of the 175 patients with COVID-19, 93 were female (53%); the median age was 50 (interquartile range [IQR], 37-63) years. The median length of hospital stay was 16 (IQR, 13-21) days, and the median disease duration was 22 (IQR, 18-26) days. Variable levels of SARS-CoV-2–specific NAbs were observed at the time of discharge (50% inhibitory dose [ID50], 1076 [IQR, 448-2048]). There were 10 patients whose NAb titers were less than the detectable level of the assay (ID50, Conclusions and Relevance In this cohort study, among 175 patients who recovered from mild COVID-19 in Shanghai, China, NAb titers to SARS-CoV-2 appeared to vary substantially. Further research is needed to understand the clinical implications of differing NAb titers for protection against future infection.

Associations of Processed Meat, Unprocessed Red Meat, Poultry, or Fish Intake With Incident Cardiovascular Disease and All-Cause Mortality

Abstract: Importance Although the associations between processed meat intake and cardiovascular disease (CVD) and all-cause mortality have been established, the associations of unprocessed red meat, poultry, or fish consumption with CVD and all-cause mortality are still uncertain. Objective To identify the associations of processed meat, unprocessed red meat, poultry, or fish intake with incident CVD and all-cause mortality. Design, Setting, and Participants This cohort study analyzed individual-level data of adult participants in 6 prospective cohort studies in the United States. Baseline diet data from 1985 to 2002 were collected. Participants were followed up until August 31, 2016. Data analyses were performed from March 25, 2019, to November 17, 2019. Exposures Processed meat, unprocessed red meat, poultry, or fish intake as continuous variables. Main Outcomes and Measures Hazard ratio (HR) and 30-year absolute risk difference (ARD) for incident CVD (composite end point of coronary heart disease, stroke, heart failure, and CVD deaths) and all-cause mortality, based on each additional intake of 2 servings per week for monotonic associations or 2 vs 0 servings per week for nonmonotonic associations. Results Among the 29 682 participants (mean [SD] age at baseline, 53.7 [15.7] years; 13 168 [44.4%] men; and 9101 [30.7%] self-identified as non-white), 6963 incident CVD events and 8875 all-cause deaths were adjudicated during a median (interquartile range) follow-up of 19.0 (14.1-23.7) years. The associations of processed meat, unprocessed red meat, poultry, or fish intake with incident CVD and all-cause mortality were monotonic (Pfor nonlinearity ≥ .25), except for the nonmonotonic association between processed meat intake and incident CVD (Pfor nonlinearity = .006). Intake of processed meat (adjusted HR, 1.07 [95% CI, 1.04-1.11]; adjusted ARD, 1.74% [95% CI, 0.85%-2.63%]), unprocessed red meat (adjusted HR, 1.03 [95% CI, 1.01-1.06]; adjusted ARD, 0.62% [95% CI, 0.07%-1.16%]), or poultry (adjusted HR, 1.04 [95% CI, 1.01-1.06]; adjusted ARD, 1.03% [95% CI, 0.36%-1.70%]) was significantly associated with incident CVD. Fish intake was not significantly associated with incident CVD (adjusted HR, 1.00 [95% CI, 0.98-1.02]; adjusted ARD, 0.12% [95% CI, −0.40% to 0.65%]). Intake of processed meat (adjusted HR, 1.03 [95% CI, 1.02-1.05]; adjusted ARD, 0.90% [95% CI, 0.43%-1.38%]) or unprocessed red meat (adjusted HR, 1.03 [95% CI, 1.01-1.05]; adjusted ARD, 0.76% [95% CI, 0.19%-1.33%]) was significantly associated with all-cause mortality. Intake of poultry (adjusted HR, 0.99 [95% CI, 0.97-1.02]; adjusted ARD, −0.28% [95% CI, −1.00% to 0.44%]) or fish (adjusted HR, 0.99 [95% CI, 0.97-1.01]; adjusted ARD, −0.34% [95% CI, −0.88% to 0.20%]) was not significantly associated with all-cause mortality. Conclusions and Relevance These findings suggest that, among US adults, higher intake of processed meat, unprocessed red meat, or poultry, but not fish, was significantly associated with a small increased risk of incident CVD, whereas higher intake of processed meat or unprocessed red meat, but not poultry or fish, was significantly associated with a small increased risk of all-cause mortality. These findings have important public health implications and should warrant further investigations.

Meeting the Care Needs of Older Adults Isolated at Home During the COVID-19 Pandemic.

Abstract: The dramatic shift toward social distancing measures presents important challenges to the health and wellbeing of community-dwelling older adults, particularly those who are frail, very old, or have multiple chronic conditions. Such older adults are at high risk of dying from COVID-19.1 Yet they also have high rates of morbidity and mortality from other acute and chronic conditions—and may adapt poorly to aggressive physical distancing and the changing health system structures that accompany it. In this Viewpoint, we highlight the health challenges for community-dwelling older adults and offer targeted suggestions for actions clinicians can take to mitigate these threats. Although loneliness and depression may result from or coexist with social isolation, they only represent the tip of the iceberg of potential harm. For many older adults, health is influenced more by their daily lives than by medical interventions. Changes in the types of foods eaten due to changes in food availability during shelterin-place orders may precipitate the exacerbation of heart failure, for example. Lack of exercise due to isolating at home may lead to deconditioning with subsequent weakness and falls. Reduction in the cognitive stimulation that comes with socializing and engaging with the wider world may worsen cognitive and behavioral symptoms of dementia.2 Older adults with medical, cognitive, or social frailty have less reserve to compensate when their homeostasis is threatened. When facing the challenges of social isolation, they are particularly vulnerable to rapid declines. Withdrawal of the formal and informal functional supports on which many vulnerable older adults rely may compound these problems. These supports can make all the difference between staying in their home or ending up in a hospital, residential care, or long-term care facility. Although policies and practices for those who provide professional services for older adults continue to evolve, many have substantially cut back on inhome supportive services, adult day health care, and other programs. Family and friends who have served as caregivers may be afraid or unable to visit. While it has been heartening to see voluntary networks spring up to help older adults buy groceries and the like, other basic needs such as assistance with bathing, basic home cleaning, and dementia supports may be unmet. Finally, when declines in health occur, fear of going to medical facilities may prevent people from receiving the care they need—a likely contributor to anecdotal reports of marked declines in hospitalization for non-COVID serious illness that have been observed in some hospitals. Moreover, the telephone and video substitutes for inperson evaluation pose special challenges for some older adults. Hearing loss, cognitive impairment, and unfamiliarity with new technology may compromise their ability to effectively use these modalities. These technology platforms have not been rigorously evaluated in older adults and may not be configured for easy use.3 Yet for many older adults they have become the sole source of connection with the health care system. All is not doom and gloom, however. Although social and health system realignments in response to COVID-19 are unavoidable, clinicians can help reduce their potentially negative effects on the health of older adults by identifying and addressing the risks and helping patients compensate. First, telephone or video visits may be improved with simple, common sense interventions. Ensure that vulnerable patients are wearing their hearing aids (or using telephonic adaptive devices, if they have them). Enlist the help of a family member, friend, paid caregiver, or staff member in advance of the visit to familiarize older adults with video-call technology. By practicing ahead of time, the UCSF Care at Home program has rapidly increased utilization of such technologies. It may also be useful to engage caregivers in a visit through a 3-way call, which can be done using apps such as Facetime or Skype, which can be used during the COVID-19 national health emergency as part of the expanded Medicare telemedicine services.4 Telemedicine only goes so far, however. There is a risk that reflexive thinking and fear among both clinicians and patients may override clinical common sense about which in-person visits are in fact essential. Clinicians should be mindful of this potential cognitive trap and advise their patients to avoid it as well. When a trip to the clinic or lab may be particularly risky or challenging, creative solutions such as home health nursing evaluation, phlebotomy, or a house call (while maintaining stringent infection control safeguards) should be considered. Second, when meeting with older patients face-toface or virtually, clinicians should inquire about unmet social or functional needs. Have informal or formal services and supports been withdrawn, and, if so, how is the person managing? How is the person getting food and staying active? If answers are concerning, additional or novel supports such as home meal delivery or emergency on-call home care services should be considered, with health system social workers and Area Agencies on Aging often having the best knowledge of options.5 Early identification of these issues may help prevent hospitalizations. Where appropriate, patients should also be encouraged to accept available home care services, which may be essential to preserve their health, but which they may have previously declined because of concerns about exposure to COVID-19. Health sysVIEWPOINT

Association Between Healthy Eating Patterns and Risk of Cardiovascular Disease

Abstract: Importance The 2015-2020 Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of cardiovascular disease (CVD). Objective To examine the associations of dietary scores for 4 healthy eating patterns with risk of incident CVD. Design, Setting, and Participants Prospective cohort study of initially healthy women from the Nurses’ Health Study (NHS) (1984-2016) and the NHS II (1991-2017) and men from the Health Professionals Follow-up Study (HPFS) (1986-2012). The dates of analysis were July 25 to December 4, 2019. Exposures Healthy Eating Index–2015 (HEI-2015), Alternate Mediterranean Diet Score (AMED), Healthful Plant-Based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). Main Outcomes and Measures Cardiovascular disease events, including fatal and nonfatal coronary heart disease (CHD) and stroke. Results The final study sample included 74 930 women in the NHS (mean [SD] baseline age, 50.2 [7.2] years), 90 864 women in the NHS II (mean [SD] baseline age, 36.1 [4.7] years), and 43 339 men in the HPFS (mean [SD] baseline age, 53.2 [9.6] years). During a total of 5 257 190 person-years of follow-up, 23 366 incident CVD cases were documented (18 092 CHD and 5687 stroke) (some individuals were diagnosed as having both CHD and stroke). Comparing the highest with the lowest quintiles, the pooled multivariable-adjusted hazard ratios (HRs) of CVD were 0.83 (95% CI, 0.79-0.86) for the HEI-2015, 0.83 (95% CI, 0.79-0.86) for the AMED, 0.86 (95% CI, 0.82-0.89) for the HPDI, and 0.79 (95% CI, 0.75-0.82) for the AHEI (Pfor trend Conclusions and Relevance In 3 large prospective cohorts with up to 32 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of CVD. These findings support the recommendations of the 2015-2020 Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure.

Abstract: This cohort study investigates whether the prone position is associated with improved oxygenation and decreased risk for intubation in spontaneously breathing patients with severe COVID-19 hypoxemic respiratory failure

Assessment of the Prevalence of Medical Student Mistreatment by Sex, Race/Ethnicity, and Sexual Orientation

Abstract: Importance Previous studies have shown that medical student mistreatment is common. However, few data exist to date describing how the prevalence of medical student mistreatment varies by student sex, race/ethnicity, and sexual orientation. Objective To examine the association between mistreatment and medical student sex, race/ethnicity, and sexual orientation. Design, Setting, and Participants This cohort study analyzed data from the 2016 and 2017 Association of American Medical Colleges Graduation Questionnaire. The questionnaire annually surveys graduating students at all 140 accredited allopathic US medical schools. Participants were graduates from allopathic US medical schools in 2016 and 2017. Data were analyzed between April 1 and December 31, 2019. Main Outcomes and Measures Prevalence of self-reported medical student mistreatment by sex, race/ethnicity, and sexual orientation. Results A total of 27 504 unique student surveys were analyzed, representing 72.1% of graduating US medical students in 2016 and 2017. The sample included the following: 13 351 female respondents (48.5%), 16 521 white (60.1%), 5641 Asian (20.5%), 2433 underrepresented minority (URM) (8.8%), and 2376 multiracial respondents (8.6%); and 25 763 heterosexual (93.7%) and 1463 lesbian, gay, or bisexual (LGB) respondents (5.3%). At least 1 episode of mistreatment was reported by a greater proportion of female students compared with male students (40.9% vs 25.2%,P Conclusions and Relevance Female, URM, Asian, multiracial, and LGB students seem to bear a disproportionate burden of the mistreatment reported in medical schools. It appears that addressing the disparate mistreatment reported will be an important step to promote diversity, equity, and inclusion in medical education.

Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis.

Abstract: Importance Risk of nephrogenic systemic fibrosis (NSF) to individual patients with stage 4 or 5 chronic kidney disease (CKD; defined as estimated glomerular filtration rate of Objective To assess the pooled risk of NSF in patients with stage 4 or 5 CKD receiving a group II GBCA. Data Sources A health sciences informationist searched the Ovid (MEDLINE and MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citation, and Daily and Versions), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Open Grey databases from inception to January 29, 2019, yielding 2700 citations. Study Selection Citations were screened for inclusion in a multistep process. Agreement for final cohort inclusion was determined by 2 blinded screeners using Cohen κ. Inclusion criteria consisted of stage 4 or 5 CKD with or without dialysis, administration of an unconfounded American College of Radiology classification group II GBCA (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, or gadoteridol), and incident NSF as an outcome. Conference abstracts, retracted manuscripts, narrative reviews, editorials, case reports, and manuscripts not reporting total group II GBCA administrations were excluded. Data Extraction and Synthesis Data extraction was performed for all studies by a single investigator, including publication details, study design and time frame, patient characteristics, group II GBCA(s) administered, total exposures for patients with stage 4 or stage 5 CKD, total cases of unconfounded NSF, reason for GBCA administration, follow-up duration, loss to follow-up, basis for NSF screening, and diagnosis. Main Outcomes and Measures Pooled incidence of NSF and the associated upper bound of a 2-sided 95% CI (risk estimate) for the pooled data and each of the 4 group II GBCAs. Results Sixteen unique studies with 4931 patients were included (κ = 0.68) in this systematic review and meta-analysis. The pooled incidence of NSF was 0 of 4931 (0%; upper bound of 95% CI, 0.07%). The upper bound varied owing to different sample sizes for gadobenate dimeglumine (0 of 3167; upper bound of 95% CI, 0.12%), gadoterate meglumine (0 of 1204; upper bound of 95% CI, 0.31%), gadobutrol (0 of 330; upper bound of 95% CI, 1.11%), and gadoteridol (0 of 230; upper bound of 95% CI, 1.59%). Conclusions and Relevance This study’s findings suggest that the risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely less than 0.07%. The potential diagnostic harms of withholding group II GBCA for indicated examinations may outweigh the risk of NSF in this population. Trial Registration PROSPERO identifier:CRD42019123284

Association of a Workplace Sales Ban on Sugar-Sweetened Beverages With Employee Consumption of Sugar-Sweetened Beverages and Health.

Abstract: Importance Reductions in sugar-sweetened beverage (SSB) intake can improve health, but are difficult for individuals to achieve on their own. Objectives To evaluate whether a workplace SSB sales ban was associated with SSB intake and cardiometabolic health among employees and whether a brief motivational intervention provides added benefits to the sales ban. Design, Setting, and Participants This before-after study and additional randomized trial conducted from July 28, 2015, to October 16, 2016, at a Northern California university and hospital assessed SSB intake, anthropometrics, and cardiometabolic biomarkers among 214 full-time English-speaking employees who were frequent SSB consumers (≥360 mL [≥12 fl oz] per day) before and 10 months after implementation of an SSB sales ban in a large workplace, with half the employees randomized to receive a brief motivational intervention targeting SSB reduction. Interventions The employer stopped selling SSBs in all workplace venues, and half the sample was randomized to receive a brief motivational intervention and the other half was a control group that did not receive the intervention. This intervention was modeled on standard brief motivational interventions for alcohol used in the workplace that promote health knowledge and goal setting. Main Outcomes and Measures Outcomes included changes in SSB intake, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and measures of abdominal adiposity. The primary associations tested were the correlation between changes in SSB intake and changes in HOMA-IR. Results Among the 214 study participants, 124 (57.9%) were women, with a mean (SD) age of 41.2 (11.0) years and a baseline mean (SD) body mass index of 29.4 (6.5). They reported a mean daily intake of 1050 mL (35 fl oz) of SSBs at baseline and 540 mL (18 fl oz) at follow-up—a 510-mL (17–fl oz) (48.6%) decrease (P Conclusions and Relevance This study’s findings suggest that the workplace sales ban was associated with a reduction in SSB intake and a significant reduction in waist circumference among employees within 10 months. The randomized clinical trial portion of this study found that targeting those at high risk with a brief motivational intervention led to additional improvements. Workplace sales bans may offer a promising new private-sector strategy for reducing the health harms of SSB intake. Trial Registration ClinicalTrials.gov identifier:NCT02585336

US Public Concerns About the COVID-19 Pandemic From Results of a Survey Given via Social Media.

Abstract: This survey study assessed public concerns about symptoms of coronavirus disease 2019 and individual actions in response to the pandemic.

Experiences of Home Health Care Workers in New York City During the Coronavirus Disease 2019 Pandemic: A Qualitative Analysis.

Abstract: Importance Home health care workers care for community-dwelling adults and play an important role in supporting patients with confirmed and suspected coronavirus disease 2019 (COVID-19) who remain at home. These workers are mostly middle-aged women and racial/ethnic minorities who typically earn low wages. Despite being integral to patient care, these workers are often neglected by the medical community and society at large; thus, developing a health care system capable of addressing the COVID-19 crisis and future pandemics requires a better understanding of the experiences of home health care workers. Objective To understand the experiences of home health care workers caring for patients in New York City during the COVID-19 pandemic. Design, setting, and participants From March to April 2020, a qualitative study with 1-to-1 semistructured interviews of 33 home health care workers in New York City was conducted in partnership with the 1199SEIU Home Care Industry Education Fund, a benefit fund of the 1199 Service Employees International Union United Healthcare Workers East, the largest health care union in the US. Purposeful sampling was used to identify and recruit home health care workers. Main outcomes and measures Audio-recorded interviews were professionally transcribed and analyzed using grounded theory. Major themes and subthemes were identified. Results In total, 33 home health care workers employed by 24 unique home care agencies across the 5 boroughs of New York City participated. Participants had a mean (SD) age of 47.6 (14.0) years, 32 (97%) were women, 21 (64%) were Black participants, and 6 (18%) were Hispanic participants. Five major themes emerged: home health care workers (1) were on the front lines of the COVID-19 pandemic but felt invisible; (2) reported a heightened risk for virus transmission; (3) received varying amounts of information, supplies, and training from their home care agencies; (4) relied on nonagency alternatives for support, including information and supplies; and (5) were forced to make difficult trade-offs in their work and personal lives. Conclusions and relevance In this qualitative analysis, home health care workers reported providing frontline essential care, often at personal risk, during the COVID-19 pandemic. They experienced challenges that exacerbated the inequities they face as a marginalized workforce. Interventions and policies to better support these frontline health care professionals are urgently needed.