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BACKGROUND: Nirmatrelvir-ritonavir is recommended for persons at risk for severe coronavirus disease 2019 (COVID-19) but remains underutilized. Information on which eligible groups are likely to benefit from treatment is needed. METHODS: We conducted a target trial emulation study in the Veterans Health Administration comparing nirmatrelvir-ritonavir treated versus matched untreated veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from April 2022 through March 2023. We measured incidence of any hospitalization or all-cause mortality at 30 days. Outcomes were measured for the entire cohort, as well as among subgroups defined by 30-day risk of death or hospitalization, estimated using an ensemble risk prediction model. RESULTS: Participants were 87% male with median age 66 years and 16% unvaccinated. Compared with matched untreated participants, those treated with nirmatrelvir-ritonavir (n = 24 205) had a lower 30-day risk for hospitalization (1.80% vs 2.30%; risk difference [RD], -0.50% points [95% confidence interval {CI}: -.69 to -.35]) and death (0.11% vs 0.30%; RD, -0.20 [95% CI: -.24 to -.13]). The greatest reductions in combined hospitalization or death were observed in the highest risk quartile (RD -2.85 [95% CI: -3.94 to -1.76]), immunocompromised persons (RD -1.91 [95% CI: -3.09 to -.74]), and persons aged ≥75 years (RD -1.16 [95% CI: -1.73 to -.59]). No reductions were observed in the 2 lowest risk quartiles or persons younger than 65 years. CONCLUSIONS: Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death in older veterans, those at highest predicted risk for severe outcomes, and immunocompromised groups. Benefit was not observed in younger veterans or groups at lower predicted risk for hospitalization and death.
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BACKGROUND: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). OBJECTIVE: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. DESIGN: Survey-based non-randomized cohort study with matched comparators. PARTICIPANTS: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. MAIN MEASURES: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. KEY RESULTS: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. CONCLUSION: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.
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COVID-19 , Depressão , Veteranos , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Depressão/epidemiologia , Depressão/psicologia , Estados Unidos/epidemiologia , Adulto , Idoso , Estudos de Coortes , SARS-CoV-2RESUMO
BACKGROUND: There is limited information on the extent and patterns of disparities in COVID-19 mortality throughout the pandemic. We aimed to examine trends in disparities by demographics over variants in the pre- and post-vaccine availability period among Californian workers using a social determinants of health lens. METHODS: Using death certificates, we identified all COVID-19 deaths that occurred between January 2020 and May 2022 among workers aged 18-64 years in California (CA). We derived estimates for at-risk worker populations using the Current Population Survey. The waves of COVID-19 mortality in the pre-vaccine availability period were March 2020-June 2020 (wave 1), and July 2020-November 2020 (wave 2), and in the post-vaccine availability period: December 2020-May 2021 (wave 3), June 2021-January 2022 (wave 4), and February 2022-May 2022 (wave 5). Poisson regression models with robust standard errors were used to determine wave-specific mortality rate ratios (MRRs). We examined the change in MRR across waves by including an interaction term between each demographic characteristic and wave period in different models. The role of potential misclassification of Race/ethnicity on death certificates was examined using probabilistic quantitative bias analysis as sensitivity analysis. RESULTS: Among the 24.1 million working age CA population included in the study, there were 26,068 COVID-19 deaths in the period between January 2020 and May 2022. Compared with their respective reference groups, workers who were 50-64 years old, male, Native Hawaiian, Latino, or African American, foreign-born; individuals who had lower education; and unmarried were disproportionately affected by COVID-19 mortality. While disparities by sex, race/ethnicity and foreign-born status narrowed in later waves (post-vaccine availability), disparities by age, education level and marital status did not change substantially across waves. CONCLUSION: Demographic disparities in COVID-19 mortality narrowed in the post-vaccine availability waves. However, the existence of disparities across all waves of the pandemic, even in an era of widespread vaccine coverage, could indicate remaining gaps in prevention and differential vulnerability. Addressing the underlying social, structural, and occupational factors that contribute to these disparities is critical for achieving health equity.
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COVID-19 , Disparidades nos Níveis de Saúde , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Adulto , Pessoa de Meia-Idade , California/epidemiologia , Masculino , Feminino , Adolescente , Adulto Jovem , Pandemias , SARS-CoV-2 , Vacinas contra COVID-19/administração & dosagem , Determinantes Sociais da SaúdeRESUMO
BACKGROUND: Research suggests an association between COVID-19 infection and certain financial hardships in the shorter term and among single-state and privately insured samples. Whether COVID-19 is associated with financial hardship in the longer-term or among socially vulnerable populations is unknown. Therefore, we examined whether COVID-19 was associated with a range of financial hardships 18 months after initial infection among a national cohort of Veterans enrolled in the Veterans Health Administration (VHA)-the largest national integrated health system in the US. We additionally explored the association between Veteran characteristics and financial hardship during the pandemic, irrespective of COVID-19. METHODS: We conducted a prospective, telephone-based survey. Out of 600 Veterans with COVID-19 from October 2020 through April 2021 who were invited to participate, 194 Veterans with COVID-19 and 194 matched comparators without a history of infection participated. Financial hardship outcomes included overall health-related financial strain, two behavioral financial hardships (e.g., taking less medication than prescribed due to cost), and seven material financial hardships (e.g., using up most or all savings). Weighted generalized estimating equations were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of financial hardship by COVID-19 status, and to assess the relationship between infection and Veteran age, VHA copay status, and comorbidity score, irrespective of COVID-19 status. RESULTS: Among 388 respondents, 67% reported at least one type of financial hardship since March 2020, with 21% reporting behavioral hardships and 64% material hardships; 8% reported severe-to-extreme health-related financial strain. Compared with uninfected matched comparators, Veterans with a history of COVID-19 had greater risks of severe-to-extreme health-related financial strain (RR: 4.0, CI: 1.4-11.2), taking less medication due to cost (RR: 2.9, 95% CI: 1.0-8.6), and having a loved one take time off work to care for them (RR: 1.9, CI: 1.1-3.6). Irrespective of COVID-19 status, Veterans aged < 65 years had a greater risk of most financial hardships compared with Veterans aged ≥ 65 years. CONCLUSIONS: Health-related financial hardships such as taking less medication due to cost and severe-to-extreme health-related financial strain were more common among Veterans with a history of COVID-19 than among matched comparators. Strategies are needed to address health-related financial hardship after COVID-19. TRIAL REGISTRATION: NCT05394025, registered 05-27-2022.
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COVID-19 , Estresse Financeiro , Veteranos , Humanos , COVID-19/epidemiologia , COVID-19/economia , Estados Unidos/epidemiologia , Estudos Prospectivos , Masculino , Feminino , Veteranos/estatística & dados numéricos , Pessoa de Meia-Idade , Estresse Financeiro/epidemiologia , Idoso , SARS-CoV-2 , Adulto , Pandemias/economia , United States Department of Veterans AffairsRESUMO
BACKGROUND: COVID-19 has been linked to the development of many post-COVID-19 conditions (PCCs) after acute infection. Limited information is available on the effectiveness of oral antivirals used to treat acute COVID-19 in preventing the development of PCCs. OBJECTIVE: To measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir-ritonavir in preventing PCCs. DESIGN: Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment. SETTING: Veterans Health Administration (VHA). PARTICIPANTS: Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022. INTERVENTION: Nirmatrelvir-ritonavir treatment for acute COVID-19. MEASUREMENTS: Cumulative incidence of 31 potential PCCs at 31 to 180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms. RESULTS: Eighty-six percent of the participants were male, with a median age of 66 years, and 17.5% were unvaccinated. Baseline characteristics were well balanced between participants treated with nirmatrelvir-ritonavir and matched untreated comparators. No differences were observed between participants treated with nirmatrelvir-ritonavir (n = 9593) and their matched untreated comparators in the incidence of most PCCs examined individually or grouped by organ system, except for lower combined risk for venous thromboembolism and pulmonary embolism (subhazard ratio, 0.65 [95% CI, 0.44 to 0.97]; cumulative incidence difference, -0.29 percentage points [CI, -0.52 to -0.05 percentage points]). LIMITATIONS: Ascertainment of PCCs using International Classification of Diseases, 10th Revision, codes may be inaccurate. Evaluation of many outcomes could have resulted in spurious associations with combined thromboembolic events by chance. CONCLUSION: Out of 31 potential PCCs, only combined thromboembolic events seemed to be reduced by nirmatrelvir-ritonavir. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.
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COVID-19 , Tromboembolia , Veteranos , Estados Unidos/epidemiologia , Humanos , Masculino , Idoso , Feminino , Tratamento Farmacológico da COVID-19 , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2 , Antivirais/uso terapêuticoRESUMO
Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.
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Monkeypox virus , Mpox , Estados Unidos/epidemiologia , Humanos , Monkeypox virus/genética , Mpox/diagnóstico , Mpox/epidemiologia , Período de Incubação de Doenças InfecciosasRESUMO
Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease, or exposure period and demographic variables are limited. During 3 to 17 November 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status, and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here, we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8 to 10 days postexposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 h for BinaxNOW and 26 h for rRT-PCR. Point-of-care antigen tests have a shorter turnaround time than laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program.
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COVID-19 , SARS-CoV-2 , Antígenos Virais , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
Work-related factors can contribute to risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, and subsequent COVID-19-attributable outcomes, including death. Comparing COVID-19 metrics across industries can help identify workers at highest risk. Elevated COVID-19 mortality rates have been reported among all transportation workers, as well as specifically in public transportation industries (1-3). The California Department of Public Health (CDPH) calculated public transportation industry-specific COVID-19 outbreak incidence during January 2020-May 2022 and analyzed all laboratory-confirmed COVID-19 deaths among working-age adults in California to calculate public transportation industry-specific mortality rates during the same period. Overall, 340 confirmed COVID-19 outbreaks, 5,641 outbreak-associated cases, and 537 COVID-19-associated deaths were identified among California public transportation industries. Outbreak incidence was 5.2 times as high (129.1 outbreaks per 1,000 establishments) in the bus and urban transit industry and 3.6 times as high in the air transportation industry (87.7) as in all California industries combined (24.7). Mortality rates were 2.1 times as high (237.4 deaths per 100,000 workers) in transportation support services and 1.8 times as high (211.5) in the bus and urban transit industry as in all industries combined (114.4). Workers in public transportation industries are at higher risk for COVID-19 workplace outbreaks and mortality than the general worker population in California and should be prioritized for COVID-19 prevention strategies, including vaccination and enhanced workplace protection measures.
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COVID-19 , Adulto , California/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , Indústrias , SARS-CoV-2RESUMO
The oxidation of proline to pyrroline-5-carboxylate (P5C) leads to the transfer of electrons to ubiquinone in mitochondria that express proline dehydrogenase (ProDH). This electron transfer supports Complexes CIII and CIV, thus generating the protonmotive force. Further catabolism of P5C forms glutamate, which fuels the citric acid cycle that yields the reducing equivalents that sustain oxidative phosphorylation. However, P5C and glutamate catabolism depend on CI activity due to NAD+ requirements. NextGen-O2k (Oroboros Instruments) was used to measure proline oxidation in isolated mitochondria of various mouse tissues. Simultaneous measurements of oxygen consumption, membrane potential, NADH, and the ubiquinone redox state were correlated to ProDH activity and F1FO-ATPase directionality. Proline catabolism generated a sufficiently high membrane potential that was able to maintain the F1FO-ATPase operation in the forward mode. This was observed in CI-inhibited mouse liver and kidney mitochondria that exhibited high levels of proline oxidation and ProDH activity. This action was not observed under anoxia or when either CIII or CIV were inhibited. The duroquinone fueling of CIII and CIV partially reproduced the effects of proline. Excess glutamate, however, could not reproduce the proline effect, suggesting that processes upstream of the glutamate conversion from proline were involved. The ProDH inhibitors tetrahydro-2-furoic acid and, to a lesser extent, S-5-oxo-2-tetrahydrofurancarboxylic acid abolished all proline effects. The data show that ProDH-directed proline catabolism could generate sufficient CIII and CIV proton pumping, thus supporting ATP production by the F1FO-ATPase even under CI inhibition.
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Prolina Oxidase , Ubiquinona , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Complexo I de Transporte de Elétrons/metabolismo , Ácido Glutâmico/metabolismo , Camundongos , Mitocôndrias/metabolismo , Prolina/metabolismo , Prolina Oxidase/metabolismo , Ubiquinona/metabolismoRESUMO
Human dihydrolipoamide dehydrogenase (hLADH, hE3) deficiency (OMIM# 246900) is an often prematurely lethal genetic disease usually caused by inactive or partially inactive hE3 variants. Here we report the crystal structure of wild-type hE3 at an unprecedented high resolution of 1.75 Å and the structures of six disease-causing hE3 variants at resolutions ranging from 1.44 to 2.34 Å. P453L proved to be the most deleterious substitution in structure as aberrations extensively compromised the active site. The most prevalent G194C-hE3 variant primarily exhibited structural alterations close to the substitution site, whereas the nearby cofactor-binding residues were left unperturbed. The G426E substitution mainly interfered with the local charge distribution introducing dynamics to the substitution site in the dimer interface; G194C and G426E both led to minor structural changes. The R460G, R447G and I445M substitutions all perturbed a solvent accessible channel, the so-called H+/H2O channel, leading to the active site. Molecular pathomechanisms of enhanced reactive oxygen species (ROS) generation and impaired binding to multienzyme complexes were also addressed according to the structural data for the relevant mutations. In summary, we present here for the first time a comprehensive study that links three-dimensional structures of disease-causing hE3 variants to residual hLADH activities, altered capacities for ROS generation, compromised affinities for multienzyme complexes and eventually clinical symptoms. Our results may serve as useful starting points for future therapeutic intervention approaches.
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Di-Hidrolipoamida Desidrogenase/deficiência , Complexos Multienzimáticos/metabolismo , Domínio Catalítico , Di-Hidrolipoamida Desidrogenase/genética , Humanos , Complexos Multienzimáticos/genética , Mutagênese Sítio-Dirigida , Mutação/genética , Conformação Proteica , Espécies Reativas de Oxigênio/metabolismoRESUMO
Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies.
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Teste Sorológico para COVID-19 , COVID-19/diagnóstico , Serviços de Saúde Comunitária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arizona/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Transmission of multidrug-resistant tuberculosis (MDRTB) requires spatial proximity between infectious cases and susceptible persons. We assess activity space overlap among MDRTB cases and community controls to identify potential areas of transmission. METHODS: We enrolled 35 MDRTB cases and 64 TB-free community controls in Lima, Peru. Cases were whole genome sequenced and strain clustering was used as a proxy for transmission. GPS data were gathered from participants over seven days. Kernel density estimation methods were used to construct activity spaces from GPS locations and the utilization distribution overlap index (UDOI) was used to quantify activity space overlap. RESULTS: Activity spaces of controls (median = 35.6 km2, IQR = 25.1-54) were larger than cases (median = 21.3 km2, IQR = 17.9-48.6) (P = 0.02). Activity space overlap was greatest among genetically clustered cases (mean UDOI = 0.63, sd = 0.67) and lowest between cases and controls (mean UDOI = 0.13, sd = 0.28). UDOI was positively associated with genetic similarity of MDRTB strains between case pairs (P < 0.001). The odds of two cases being genetically clustered increased by 22% per 0.10 increase in UDOI (OR = 1.22, CI = 1.09-1.36, P < 0.001). CONCLUSIONS: Activity space overlap is associated with MDRTB clustering. MDRTB transmission may be occurring in small, overlapping activity spaces in community settings. GPS studies may be useful in identifying new areas of MDRTB transmission.
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Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/transmissão , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Adulto , Feminino , Sistemas de Informação Geográfica , Humanos , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Rede Social , Adulto JovemRESUMO
PURPOSE: This study describes challenges faced while incorporating sometimes conflicting stakeholder feedback into study design and development of patient-facing materials for a translational genomics study aiming to reduce health disparities among diverse populations. METHODS: We conducted an ethnographic analysis of study documents including summaries of patient advisory committee meetings and interviews, reflective field notes written by study team members, and correspondence with our institutional review board (IRB). Through this analysis, we identified cross-cutting challenges for incorporating stakeholder feedback into development of our recruitment, risk assessment, and informed consent processes and materials. RESULTS: Our analysis revealed three key challenges: (1) balancing precision and simplicity in the design of study materials, (2) providing clinical care within the research context, and (3) emphasizing potential study benefits versus risks and limitations. CONCLUSIONS: While involving patient stakeholders in study design and materials development can increase inclusivity and responsiveness to patient needs, patient feedback may conflict with that of content area experts on the research team and IRBs who are tasked with overseeing the research. Our analysis highlights the need for further empirical research about ethical challenges when incorporating patient feedback into study design, and for dialogue with genomic researchers and IRB representatives about these issues.
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Comitês de Ética em Pesquisa , Genômica , Retroalimentação , Humanos , Consentimento Livre e Esclarecido , PesquisadoresRESUMO
Nursing homes are high-risk settings for outbreaks of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1,2). During the COVID-19 pandemic, U.S. health departments worked to improve infection prevention and control (IPC) practices in nursing homes to prevent outbreaks and limit the spread of COVID-19 in affected facilities; however, limited resources have hampered health departments' ability to rapidly provide IPC support to all nursing homes within their jurisdictions. Since 2008, the Centers for Medicare & Medicaid Services (CMS) has published health inspection results and quality ratings based on their Five-Star Quality Rating System for all CMS-certified nursing homes (3); these ratings might be associated with facility-level risk factors for COVID-19 outbreaks. On April 17, 2020, West Virginia became the first state to mandate and conduct COVID-19 testing for all nursing home residents and staff members to identify and reduce transmission of SARS-CoV-2 in these settings (4). West Virginia's census of nursing home outbreaks was used to examine associations between CMS star ratings and COVID-19 outbreaks. Outbreaks, defined as two or more cases within 14 days (with at least one resident case), were identified in 14 (11%) of 123 nursing homes. Compared with 1-star-rated (lowest rated) nursing homes, the odds of a COVID-19 outbreak were 87% lower among 2- to 3-star-rated facilities (adjusted odds ratio [aOR] = 0.13, 95% confidence interval [CI] = 0.03-0.54) and 94% lower among 4- to 5-star-rated facilities (aOR = 0.06, 95% CI = 0.006-0.39). Health departments could use star ratings to help identify priority nursing homes in their jurisdictions to inform the allocation of IPC resources. Efforts to mitigate outbreaks in high-risk nursing homes are necessary to reduce overall COVID-19 mortality and associated disparities. Moreover, such efforts should incorporate activities to improve the overall quality of life and care of nursing home residents and staff members and address the social and health inequities that have been recognized as a prominent feature of the COVID-19 pandemic in the United States (5).
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Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Qualidade da Assistência à Saúde/normas , Idoso , COVID-19 , Centers for Medicare and Medicaid Services, U.S. , Humanos , Casas de Saúde/normas , Pandemias , Medição de Risco/métodos , Estados Unidos/epidemiologia , West Virginia/epidemiologiaRESUMO
Coronavirus disease 2019 (COVID-19) has had a substantial impact on racial and ethnic minority populations and essential workers in the United States, but the role of geographic social and economic inequities (i.e., deprivation) in these disparities has not been examined (1,2). As of July 9, 2020, Utah had reported 27,356 confirmed COVID-19 cases. To better understand how area-level deprivation might reinforce ethnic, racial, and workplace-based COVID-19 inequities (3), the Utah Department of Health (UDOH) analyzed confirmed cases of infection with SARS-CoV-2 (the virus that causes COVID-19), COVID-19 hospitalizations, and SARS-CoV-2 testing rates in relation to deprivation as measured by Utah's Health Improvement Index (HII) (4). Age-weighted odds ratios (weighted ORs) were calculated by weighting rates for four age groups (≤24, 25-44, 45-64, and ≥65 years) to a 2000 U.S. Census age-standardized population. Odds of infection increased with level of deprivation and were two times greater in high-deprivation areas (weighted OR = 2.08; 95% confidence interval [CI] = 1.99-2.17) and three times greater (weighted OR = 3.11; 95% CI = 2.98-3.24) in very high-deprivation areas, compared with those in very low-deprivation areas. Odds of hospitalization and testing also increased with deprivation, but to a lesser extent. Local jurisdictions should use measures of deprivation and other social determinants of health to enhance transmission reduction strategies (e.g., increasing availability and accessibility of SARS-CoV-2 testing and distributing prevention guidance) to areas with greatest need. These strategies might include increasing availability and accessibility of SARS-CoV-2 testing, contact tracing, isolation options, preventive care, disease management, and prevention guidance to facilities (e.g., clinics, community centers, and businesses) in areas with high levels of deprivation.
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Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Áreas de Pobreza , Adulto , Idoso , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/diagnóstico , Humanos , Incidência , Pessoa de Meia-Idade , Fatores de Risco , Utah/epidemiologia , Adulto JovemRESUMO
Improved understanding of the overall distribution of workplace coronavirus disease 2019 (COVID-19) outbreaks by industry sector could help direct targeted public health action; however, this has not been described. The Utah Department of Health (UDOH) analyzed COVID-19 surveillance data to describe workplace outbreaks by industry sectors. In this report, workplaces refer to non-health care, noncongregate-living, and noneducational settings. As of June 5, 2020, UDOH reported 277 COVID-19 outbreaks, 210 (76%) of which occurred in workplaces. Approximately 12% (1,389 of 11,448) of confirmed COVID-19 cases in Utah were associated with workplace outbreaks. The 210 workplace outbreaks occurred in 15 of 20 industry sectors;* nearly one half of all workplace outbreaks occurred in three sectors: Manufacturing (43; 20%), Construction (32; 15%) and Wholesale Trade (29; 14%); 58% (806 of 1,389) of workplace outbreak-associated cases occurred in these three sectors. Although 24% of Utah's workforce in all 15 affected sectors identified as Hispanic or Latino (Hispanic) or a race other than non-Hispanic white (nonwhite) (1), 73% (970 of 1,335) of workplace outbreak-associated COVID-19 cases were in persons who identified as Hispanic or nonwhite. Systemic social inequities have resulted in the overrepresentation of Hispanic and nonwhite workers in frontline occupations where exposure to SARS-CoV-2, the virus that causes COVID-19, might be higher (2); extra vigilance in these sectors is needed to ensure prevention and mitigation strategies are applied equitably and effectively to workers of racial and ethnic groups disproportionately affected by COVID-19. Health departments can adapt workplace guidance to each industry sector affected by COVID-19 to account for different production processes and working conditions.
Assuntos
Infecções por Coronavirus/etnologia , Surtos de Doenças , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Indústrias/estatística & dados numéricos , Doenças Profissionais/etnologia , Pneumonia Viral/etnologia , Grupos Raciais/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Utah/epidemiologia , Local de Trabalho , Adulto JovemRESUMO
BACKGROUND: The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls. METHODS: We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network. RESULTS: We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected. CONCLUSIONS: Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission.
Assuntos
Busca de Comunicante/estatística & dados numéricos , Farmacorresistência Bacteriana Múltipla , Mycobacterium tuberculosis/genética , Rede Social , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Adulto , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Comércio , Feminino , Instalações de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Filmes Cinematográficos , Família Multigênica , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Peru/epidemiologia , Instituições Acadêmicas , Meios de Transporte , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
The reaction catalyzed by succinate-CoA ligase in the mitochondrial matrix yields a high-energy phosphate when operating towards hydrolysis of the thioester bond of succinyl-CoA, known as mitochondrial substrate-level phosphorylation (mSLP). The catabolism of several metabolites converge to succinyl-CoA but through different biochemical pathways. Among them, threonine, serine and methionine catabolize to succinyl-CoA through the common intermediate, 2-ketobutyrate. During the course of this pathway 2-ketobutyrate will become succinyl-CoA through propionyl-CoA catabolism, obligatorily passing through an ATP-consuming step substantiated by propionyl-CoA carboxylase. Here, by recording the directionality of the adenine nucleotide translocase while measuring membrane potential we tested the hypothesis that catabolism of 2-ketobutyrate negates mSLP due to the ATP-consuming propionyl-CoA carboxylase step in rotenone-treated, isolated mouse liver and brain mitochondria. 2-Ketobutyrate produced a less negative membrane potential compared to NADH or FADH2-linked substrates, which was sensitive to inhibition by rotenone, atpenin and arsenate, implying the involvement of complex I, complex II and a dehydrogenase-most likely branched chain keto-acid dehydrogenase, respectively. Co-addition of 2-ketobutyrate with NADH- or FADH2-linked substrates yielded no greater membrane potential than in the presence of substrates alone. However, in the presence of NADH-linked substrates, 2-ketobutyrate prevented mSLP in a dose-dependent manner. Our results imply that despite that 2-ketobutyrate leads to succinyl-CoA formation, obligatory metabolism through propionyl-CoA carboxylase associated with ATP expenditure abolishes mSLP. The provision of metabolites converging to 2-ketobutyrate may be a useful way for manipulating mSLP without using pharmacological or genetic tools.
Assuntos
Acil Coenzima A/metabolismo , Butiratos/farmacologia , Mitocôndrias/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Acil Coenzima A/efeitos dos fármacos , Animais , Camundongos , Mitocôndrias/metabolismo , Fosforilação/fisiologia , Rotenona/farmacologia , Especificidade por Substrato/efeitos dos fármacosRESUMO
BACKGROUND: Major changes to the teaching of anatomy associated with the integration of basic and clinical sciences in modern medical curricula have coincided with students reporting concern over achievement of learning outcomes in anatomy. Little guidance exists for medical educators designing anatomy courses that account for factors that positively influence medical student confidence in their own anatomy knowledge. We sought to determine what factors are associated with medical students' self-reported confidence in their anatomy knowledge in preparation for clinical practice. METHODS: Cross-sectional national survey of Australian medical students distributed using social media. We performed univariate and multivariable ordinal regression to determine the factors in anatomy learning and teaching that influence medical student self-reported confidence to have sufficient anatomy knowledge by the time of graduation, for practice as a junior doctor. RESULTS: Of 1309 surveyed, 1101 (84%) responded, representing 6.5% of the Australian medical student population. Mean age was 23.9 years (SD 4.8 years), a majority were female (644, 58.5%), and students in all years of both undergraduate (52%, 575) and graduate entry courses (48%, 529) were represented. Items associated with increased self-reported confidence in anatomy knowledge included adequate assessment of anatomy (Odds Ratio 2.17 [95% CI 1.69-2.81]), integration of anatomy with other basic sciences (OR 1.97 [1.52-2.56]) and clinical teaching (OR 1.90 [1.46-2.48]), male gender (OR 1.89 [1.48-2.42]), anatomy education prior to medical school (OR 1.46 [1.14-1.87]) and exposure to dissection (OR 1.39 [1.08-1.78]). Medical students in their clinical years reported lower confidence in their anatomy knowledge (OR 0.6 [0.47-0.77], p < 0.0001). Age and career intention were not significant predictors of confidence. CONCLUSIONS: Medical educators can enhance student confidence in their own anatomy knowledge by developing curricula that vertically integrating anatomy learning and teaching, integrate anatomy teaching with other basic sciences, and providing consistent assessment through both the pre-clinical and clinical stages of medical training. Anatomy education should also incorporate dissection as a teaching method, and students could benefit from completion of anatomy education prior to medical school. Consideration should also be given to further investigate the confidence of female students in their anatomy knowledge.