RESUMEN
BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.).
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adulto , Anciano , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Neutralizantes/efectos adversos , Antivirales/efectos adversos , COVID-19/mortalidad , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Hospitalización , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Insuficiencia del TratamientoRESUMEN
Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P < 0.001) and more had a comorbidity (84% vs. 70%; P < 0.001). Of 170 discordant participants, 106 (62%) had postdischarge events captured by the TICO approach. Conclusions: Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered "recovered" using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.
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COVID-19 , Cuidados Posteriores , Anciano , Anticuerpos Monoclonales , Humanos , Alta del Paciente , SARS-CoV-2 , Resultado del TratamientoRESUMEN
BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/uso terapéutico , Anciano , Alanina/efectos adversos , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Neutralizantes/efectos adversos , Anticuerpos Neutralizantes/sangre , Antígenos Virales/sangre , Antivirales/efectos adversos , Biomarcadores/sangre , COVID-19/sangre , COVID-19/virología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Inutilidad Médica , Persona de Mediana Edad , ARN Viral/sangre , SARS-CoV-2 , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.
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COVID-19 , Adulto , COVID-19/terapia , Estudios Transversales , Humanos , Masculino , Nucleocápside , SARS-CoV-2RESUMEN
BACKGROUND/AIMS: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. METHODS: Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. Therapeutics for Inpatients with COVID-19 utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and Data and Safety Monitoring Board schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. RESULTS: As of 8 August 2021, five agents have entered the Therapeutics for Inpatients with COVID-19 master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement Therapeutics for Inpatients with COVID-19 across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. CONCLUSION: Through a robust multi-network partnership, the Therapeutics for Inpatients with COVID-19 protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak.
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Antivirales , Tratamiento Farmacológico de COVID-19 , Adulto , Antivirales/uso terapéutico , Hospitalización , Humanos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Mental health data from the 2016-2017 Vietnam Era Health Retrospective Observational Study (VE-HEROeS) were analyzed by cohort, represented by United States Vietnam theater veterans (VTs) who served in Vietnam, Cambodia, and Laos; nontheater veterans (NTs) without theater service; and age- and sex-matched nonveterans (NVs) without military service. The exposure of interest was Vietnam theater service. Surveys mailed to random samples of veterans (n = 42,393) and nonveterans (n = 6,885) resulted in response rates of 45.0% for veterans (n = 6,735 VTs, Mage = 70.09, SE = 0.04; n = 12,131 NTs) and 67.0% for NVs (n = 4,530). We examined self-report data on four mental health outcomes: probable posttraumatic stress disorder (PTSD), depression, psychological distress, and overall mental health functioning. Weighted adjusted odds ratios (aORs) between each outcome and cohort were estimated, controlling for covariates in four models: cohort plus sociodemographic variables (Model 1), Model 1 plus physical health variables (Model 2), Model 2 plus potentially traumatic events (PTEs; Model 3), and Model 3 plus other military service variables (Model 4). Mental health outcome prevalence was highest for VTs versus other cohorts, with the largest aOR, 2.88, for PTSD, 95% CI [2.46, 3.37], p < .001 (Model 4, VT:NT). Physical health and PTEs contributed most to observed effects; other service variables contributed least to aORs overall. Mental health dysfunction persists among VTs years after the war's end. The present results reaffirm previous findings and highlight the need for continued mental health surveillance in VTs.
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Trastornos por Estrés Postraumático , Veteranos , Anciano , Humanos , Salud Mental , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Estados Unidos/epidemiología , Veteranos/psicología , Vietnam/epidemiología , Guerra de VietnamRESUMEN
BACKGROUND: Research on chronic obstructive pulmonary disease (COPD) and herbicide exposure in Vietnam War veterans is limited. METHODS: Survey data were collected from 3193 US Army Chemical Corps veterans on herbicide exposure and self-reported physician-diagnosed COPD. Three spirometric patterns were used to define airflow obstruction (AFO): (i) FEV1 /FVC < 70% ("fixed ratio"); (ii) FEV1 /FVC < lower limit of normal ("LLN"); and (iii) (FEV1 /FVC < LLN and FVC ≥ LLN and FEV1 Asunto(s)
Herbicidas
, Exposición Profesional/estadística & datos numéricos
, Enfermedad Pulmonar Obstructiva Crónica/epidemiología
, Veteranos/estadística & datos numéricos
, Guerra de Vietnam
, Anciano
, Estudios de Cohortes
, Volumen Espiratorio Forzado
, Humanos
, Masculino
, Persona de Mediana Edad
, Prevalencia
, Enfermedad Pulmonar Obstructiva Crónica/fisiopatología
, Análisis de Regresión
, Estudios Retrospectivos
, Autoinforme
, Fumar/epidemiología
, Espirometría
, Estados Unidos/epidemiología
, Capacidad Vital
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X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval, the dose was increased to 0.05 mg/kg for an additional 22 weeks of treatment. Although specific antibody responses to T cell-dependent antigens was lacking, administration of rCD40 resulted in acquisition of the capacity to mount cutaneous delayed type hypersensitivity reactions that disappeared during the drug-free interval as well as the postbiologic follow-up period. With rCD40L treatment, patient T cells developed a new capacity to respond to T-cell mitogens with synthesis of IFN-γ and TNF-α. Intracellular cytokine staining studies showed that both CD4(+) and CD8(+) T cells participated in this response. Finally, CD40L therapy was associated with changes in lymph node size and architecture based on comparison of biopsies taken before and after therapy. This clinical study showed that rCD40L is capable of improving T cell-immune function in patients with XHM.
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Ligando de CD40/uso terapéutico , Síndrome de Inmunodeficiencia con Hiper-IgM Tipo 1/inmunología , Síndrome de Inmunodeficiencia con Hiper-IgM Tipo 1/terapia , Proteínas Recombinantes/uso terapéutico , Adolescente , Animales , Ligando de CD40/administración & dosificación , Ligando de CD40/efectos adversos , Ligando de CD40/inmunología , Niño , Estudios de Seguimiento , Humanos , Síndrome de Inmunodeficiencia con Hiper-IgM Tipo 1/patología , Inmunoterapia , Interferón gamma/inmunología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Ratones , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/patología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVES: We measured HIV testing and seropositivity among veterans in Veterans Affairs (VA) care for calendar years 2009 through 2011 and analyzed 2011 results by patient demographics. METHODS: We performed a repeated-measures cross-sectional study using standardized electronic data extraction from the VA electronic health records for all veterans with at least 1 outpatient visit during 2009 through 2011. We analyzed testing rates and seropositivity by demographic characteristics for 2011. RESULTS: Of veterans with an outpatient visit, 20.0% had an HIV test in 2011, compared with 9.2% in 2009. Documented HIV testing rates were highest in women and Blacks. Of confirmed positive test results, 67.0% were in outpatients older than 50 years. Seropositivity was highest among men aged 30 to 49 years, women aged 50 to 69 years, and Black outpatients of both genders. Implementation of an electronic clinical reminder was associated with higher testing rates. CONCLUSIONS: The significant effect of an electronic clinical reminder suggests that such decision support tools can substantially increase testing rates. The frequency of positive test results in older individuals suggests the need for additional work to define optimum approaches to HIV testing in this population.
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Seropositividad para VIH/diagnóstico , Tamizaje Masivo/estadística & datos numéricos , United States Department of Veterans Affairs , Adulto , Anciano , Estudios Transversales , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Seropositividad para VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Grupos Raciales , Distribución por Sexo , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Our objectives were to 1) understand the scope of the current mortality literature on U.S. women Vietnam War-era veterans and 2) identify major themes and knowledge gaps that might guide future research. METHODS: A systematic scoping review was conducted. Electronic bibliographic databases were searched for studies published on women Vietnam War-era veterans' mortality between 1973 and 2020. Inclusion and exclusion criteria were applied, study information was charted using pre-established design parameters, and studies deemed eligible were retained for a more in-depth review. FINDINGS: One hundred nineteen studies were initially identified. Of these, six were ultimately retained for critical review. External cause, all-cause, cancer, and cardiovascular mortality were prominent outcomes across studies. Although both methodology and outcomes varied by study, unifying themes emerged. Prominent themes included a) historic barriers to accurately identifying and classifying this veteran cohort, b) historic barriers to comprehensive assessment of their health and mortality risk, and c) the healthy soldier effect and its limitations. Research gaps identified in this review reflect a need to pay more attention to sex differences in mortality risk and military occupational and sex-specific health risk confounders in mortality models. CONCLUSIONS: The research literature examining mortality among women Vietnam War-era veterans is circumscribed in size and scope. Questions about the roles of salient military occupational exposures and health risk factors on mortality risks and trends in this cohort remain unaddressed. These questions should be areas of focus in next steps research.
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Personal Militar , Veteranos , Femenino , Humanos , Masculino , Vietnam , Factores de Riesgo , Guerra de VietnamRESUMEN
Background: The US Department of Veterans Affairs (VA) Office of Research and Development (ORD) supports an extensive clinical trials enterprise. Until recently, external partnerships were limited. The VA's potential value as a partner became more apparent during the COVID-19 pandemic because of its large health care system, diverse patient population, and expertise in conducting clinical trials. Observations: By leveraging its infrastructure, the VA was able to participate in 7 large-scale COVID-19 therapeutic and vaccine trials. A key aspect of this enterprise approach is the ability to provide centralized direction and coordination. The VA's partnerships with external groups offered insights into the challenges associated with conducting important trials, especially when rapidity and coordination were essential. The ORD also developed solutions for reducing study startup time that could be established as best practices. We offer lessons for the challenges VA faced: site infrastructure needs and capabilities; study management roles and responsibilities; educational resources; local review; study design demands; contracting and budgeting; central-level systems; and communication. Conclusions: VA participation in major COVID-19 therapeutic and vaccine trials represented a significant part of its research response to the pandemic. These contributions extended beyond the participants, scientists, and data that helped inform subsequent regulatory approvals. The VA also had an opportunity to directly develop partnerships with non-VA groups. These groups became more familiar with the VA while enabling us to gain more experience in the diverse practices used to conduct multisite clinical studies. Ultimately, these efforts empower the VA to further serve the broader scientific and clinical communities.
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Background: The US Department of Veterans Affairs (VA) enterprise approach to research (VA Research) has built a data-sharing framework available to all research teams within VA. Combined with robust analytic systems and tools available for investigators, VA Research has produced actionable results during the COVID-19 pandemic. Big data science techniques applied to VA's health care data demonstrate that medical research can be performed quickly and judiciously during nationwide health care emergencies. Observations: We envision a common framework of data collection, management, and surveillance implemented in partnership with other health care agencies that would capture even broader, actionable, and timely observational data on populations, while providing opportunities for enhanced collaborative research across agencies. This model should be continued and expanded through the current COVID-19 and future pandemics. Conclusions: Extending the achievements of VA Research in the COVID-19 pandemic to date, we advocate national goals of open science by working toward a synergistic national framework of anonymized, synchronized, shared health data that would provide researchers with potent tools to combat future public health crises.
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Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in vaccinated immunocompromised patients, particularly after the emergence of the Omicron variant. In this retrospective cohort study with exact matching and propensity score adjustment within the U.S. Department of Veterans Affairs (VA) healthcare system, we selected immunocompromised veterans age ≥18 years as of 1 January 2022, receiving VA healthcare. We compared a cohort of 1,878 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to 7,014 matched controls selected from patients who met study criteria but were not treated. Patients were followed through 15 June 2022, or until death, whichever occurred earlier. The primary outcome was a composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used Cox proportional hazards modeling to estimate the hazard ratios (HRs) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Most (73%) tixagevimab/cilgavimab recipients were ≥65 years old, and 80% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to matched controls, recipients had a lower incidence of the composite COVID-19 outcome (49/1,878 [2.6%] versus 312/7,014 [4.4%]; HR 0.35; 95% CI, 0.24-0.52), and individually SARS-CoV-2 infection (HR 0.44; 95% CI, 0.22-0.88), COVID-19 hospitalization (HR 0.24; 95% CI, 0.10-0.59), and all-cause mortality (HR 0.32; 95% CI, 0.19-0.55). In conclusion, tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 during the Omicron BA.1, BA.2, and BA.2.12.1 surge. IMPORTANCE SARS-CoV-2 remains an ongoing global health crisis that justifies continued efforts to validate and expand, when possible, knowledge on the efficacy of available vaccines and treatments. Clinical trials have been limited due to fast tracking of medications for mitigation of the COVID-19 pandemic for the general population. We present a real-world analysis, using electronic health record data, of the effectiveness of tixagevimab/cilgavimab for the prevention of COVID-19 infection in the unique population of U.S. veterans. Unlike those in the PROVENT clinical trial from which the emergency use authorization for tixagevimab/cilgavimab as a preventative treatment arose, the veterans population is highly immunocompromised and nearly 96% totally vaccinated. These demographics allowed us to analyze the effectiveness of tixagevimab/cilgavimab in preventing COVID-19 under different conditions in a more fragile population than that of the initial clinical trial.
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COVID-19 , Adolescente , Anciano , Humanos , COVID-19/prevención & control , Electrónica , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiología , Salud de los Veteranos , AdultoRESUMEN
In September 2020, the Department of Veterans Affairs (VA) launched a novel volunteer research registry to rapidly recruit eligible study participants for research on SARS-CoV-2 and COVID-19 vaccines and treatments at VA Medical Centers selected as study sites for COVID-19 clinical trials. Targeted multimedia outreach campaigns were used to recruit diverse populations, including those historically under-represented in medical research. By November 2022, 58,561 volunteers were enrolled in the registry, 19% of whom were women, 9% Hispanic/Latino, and 8% Black. The registry's strategic approach to outreach proved successful in recruiting diverse volunteers, with geotargeted e-mails recruiting the most diversity.
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Importance: There are persistent questions about suicide deaths among US veterans who served in the Vietnam War. It has been believed that Vietnam War veterans may be at an increased risk for suicide. Objective: To determine whether military service in the Vietnam War was associated with an increased risk of suicide, and to enumerate the number of suicides and analyze patterns in suicides among Vietnam War theater veterans compared with the US population. Design, Setting, and Participants: This cohort study compiled a roster of all Vietnam War-era veterans and Vietnam War theater veterans who served between February 28, 1961, and May 7, 1975. The 2 cohorts included theater veterans, defined as those who were deployed to the Vietnam War, and nontheater veterans, defined as those who served during the Vietnam War era but were not deployed to the Vietnam War. Mortality in these 2 cohorts was monitored from 1979 (beginning of follow-up) through 2019 (end of follow-up). Data analysis was performed between January 2022 and July 2023. Main Outcomes and Measures: The outcome of interest was death by suicide occurring between January 1, 1979, and December 31, 2019. Suicide mortality was ascertained from the National Death Index. Hazard ratios (HRs) that reflected adjusted associations between suicide risk and theater status were estimated with Cox proportional hazards regression models. Standardized mortality rates (SMRs) were calculated to compare the number of suicides among theater and nontheater veterans with the expected number of suicides among the US population. Results: This study identified 2â¯465â¯343 theater veterans (2â¯450â¯025 males [99.4%]; mean [SD] age at year of entry, 33.8 [6.7] years) and 7â¯122â¯976 nontheater veterans (6â¯874â¯606 males [96.5%]; mean [SD] age at year of entry, 33.3 [8.2] years). There were 22â¯736 suicides (24.1%) among theater veterans and 71â¯761 (75.9%) among nontheater veterans. After adjustments for covariates, Vietnam War deployment was not associated with an increased risk of suicide (HR, 0.94; 95% CI, 0.93-0.96). There was no increased risk of suicide among either theater (SMR, 0.97; 95% CI, 0.96-0.99) or nontheater (SMR, 0.97; 95% CI, 0.97-0.98) veterans compared with the US population. Conclusions and Relevance: This cohort study found no association between Vietnam War-era military service and increased risk of suicide between 1979 and 2019. Nonetheless, the 94â¯497 suicides among all Vietnam War-era veterans during this period are noteworthy and merit the ongoing attention of health policymakers and mental health professionals.
Asunto(s)
Suicidio , Veteranos , Masculino , Humanos , Estudios de Cohortes , Vietnam/epidemiología , Análisis de DatosRESUMEN
Objectives: To examine differences in potentially traumatic events (PTEs), probable PTSD, and health-related quality of life (HRQoL) between lesbian, gay, and bisexual (LGB) and heterosexual Vietnam Era veterans. Method: Data are from the 2016-2017 Vietnam Era Health Retrospective Observational study survey (n = 18,866; 45% response rate). PTEs were defined using the 10-item Brief Trauma Questionnaire and a dichotomous item about whether respondents witnessed sexual assault during military service. Current probable PTSD was measured with the Primary Care PTSD Screen, and mental and physical HRQoL was assessed with the SF-8™. Multivariable regression analyses were first adjusted for sociodemographic and military-related characteristics, and then with PTEs as a count variable ranging from 0-11. Survey weights accounted for the complex sampling design and nonresponse. Results: Approximately 1.5% of veterans were LGB. Compared to heterosexual veterans, LGB veterans were more likely to report exposure to natural disasters, childhood physical abuse, adulthood physical assault, and sexual assault, and they were less likely to report combat exposure, witnessing someone being seriously injured or killed, or witnessing sexual assault while in the military. Compared to heterosexual veterans, LGB veterans had greater odds of current probable PTSD (adjusted odds ratio [aOR] = 1.50, 95% CI [1.04, 2.16]) and poorer mental HRQoL (B = -1.70, SE = .72, p = .018). PTEs attenuated sexual orientation differences in probable PTSD (aOR = 1.27, 95% CI [.82, 1.97]) and poorer mental HRQoL (B = -1.22, SE = .67, p = .067). Conclusions: Among Vietnam Era veterans, PTEs differ based on sexual orientation, and contribute to LGB veterans' greater prevalence of current probable PTSD and poorer mental HRQoL relative to heterosexual veterans. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Asunto(s)
Minorías Sexuales y de Género , Veteranos , Adulto , Niño , Femenino , Heterosexualidad , Humanos , Masculino , Calidad de Vida , Conducta Sexual , VietnamRESUMEN
The protection provided by natural versus hybrid immunity from COVID-19 is unclear. We reflect on the challenges from trying to conduct a randomized post-SARS-CoV-2 infection vaccination trial study with rapidly evolving scientific data, vaccination guidelines, varying international policies, difficulties with vaccine availability, vaccine hesitancy, and a constantly evolving virus.