RESUMO
The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
Assuntos
Anticorpos Antivirais , COVID-19 , Evasão da Resposta Imune , SARS-CoV-2 , Humanos , Anticorpos Monoclonais , Anticorpos Neutralizantes , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19 , SARS-CoV-2/classificação , SARS-CoV-2/genéticaRESUMO
Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxic chemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature of CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8+ T cells in human lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos T CD8-Positivos , ImunoterapiaRESUMO
OBJECTIVE: This work examines the relationship between local flavor policy exposure and any tobacco product use and flavored tobacco product use among U.S. youth and young adults, as well as the equity potential of these policies by race/ethnicity. METHODS: Participants were aged 15-36 (n = 10,893) surveyed from September-December 2019 using national, address- and probability-based sampling. Local flavor policies enacted before survey completion were linked to participant home address. Weighted cross-sectional multivariable logistic regression examined individual coverage by flavor policy vs. no flavor policy, with current any tobacco or flavored tobacco use, controlling for individual and county-level demographics, psychosocial variables, and other tobacco control policies. Interactions between race/ethnicity and any tobacco use and flavored tobacco use were assessed. RESULTS: Those covered by a flavor policy vs. no policy had lower odds of any tobacco use (aOR = 0.74, 95% CI = 0.55-1.00) and current flavored tobacco use (aOR = 0.67, 95% CI = 0.48-0.93). Compared with Non-Hispanic (NH)-White individuals, NH-Black individuals (aOR = 1.08, CI = 1.04-1.12) had higher odds of any tobacco use, and non-Hispanic Asian individuals had lower odds of any tobacco use (aOR = 0.67, CI = 0.53-0.85). Hispanic individuals exposed to policy had lower odds of flavored tobacco use compared to NH-White peers. CONCLUSIONS: Exposure to flavor restriction policies is associated with lower odds of any tobacco and flavored use among youth and young adults. Flavor restrictions may be beneficial in reducing tobacco use in youth from diverse racial/ethnic backgrounds. However, passing policies covering NH-Black individuals is needed to mitigate disparities in tobacco use by flavor policy coverage over time.
RESUMO
Sexual and gender minority (SGM) adults experience poor health outcomes, in part due to frequent avoidance of necessary health care. Little is known, however, about factors contributing to patterns of health care utilization in this population. Using national data from the All of Us Research Program, this study evaluated the prevalence of care avoidance due to patient-clinician identity discordance (PCID) and its association with health care discrimination among SGM adults. Sexual minority (20.0% vs 9.4%; adjusted rate ratio [aRR] = 1.58; 95% CI, 1.49-1.67, P <0.001) and gender minority adults (34.4% vs 10.3%; aRR = 2.00; 95% CI, 1.79-2.21, P <0.001) were significantly more likely than their non-SGM counterparts to report care avoidance due to PCID. Exposure to health care discrimination was also more prevalent in this population and was dose-dependently associated with significantly higher rates of PCID-based care avoidance. Study findings highlight the importance of diversifying the health care workforce, expanding SGM-related clinical training, and preventing health care discrimination against SGM patients.
Assuntos
Minorias Sexuais e de Gênero , Humanos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estados Unidos , Relações Médico-Paciente , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adolescente , IdosoRESUMO
BACKGROUND: Accurate estimation of SARS-CoV-2 re-infection is crucial to understanding the connection between infection burden and adverse outcomes. However, relying solely on PCR testing results in underreporting. We present a novel approach that includes longitudinal serologic data, and compared it against testing alone among people experiencing homelessness. METHODS: We recruited 736 individuals experiencing homelessness in Toronto, Canada, between June and September 2021. Participants completed surveys and provided saliva and blood serology samples every three months over 12 months of follow-up. Re-infections were defined as: positive PCR or rapid antigen test (RAT) results > 90 days after initial infection; new serologic evidence of infection among individuals with previous infection who sero-reverted; or increases in anti-nucleocapsid in seropositive individuals whose levels had begun to decrease. RESULTS: Among 381 participants at risk, we detected 37 re-infections through PCR/RAT and 98 re-infections through longitudinal serology. The comprehensive method identified 37.4 re-infection events per 100 person-years, more than four-fold more than the rate detected through PCR/RAT alone (9.0 events/100 person-years). Almost all test-confirmed re-infections (85%) were also detectable by longitudinal serology. CONCLUSIONS: Longitudinal serology significantly enhances the detection of SARS-CoV-2 re-infections. Our findings underscore the importance and value of combining data sources for effective research and public health surveillance.
Assuntos
COVID-19 , Pessoas Mal Alojadas , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2/genética , Reinfecção , Canadá/epidemiologiaRESUMO
PURPOSE OF REVIEW: To summarize and evaluate the literature on treatment approaches for oligometastatic and locally recurrent urothelial cancer. RECENT FINDINGS: There is no clear definition for oligometastatic urothelial cancers due to limited data. Studies focusing on oligometastatic and locally recurrent urothelial cancer have been primarily retrospective. Treatment options include local therapy with surgery or radiation, and generalized systemic therapy such as chemotherapy or immunotherapy. Oligometastatic and locally recurrent urothelial cancers remain challenging to manage, and treatment requires an interdisciplinary approach. Systemic therapy is nearly always a component of current care in the form of chemotherapy, but the role of immunotherapy has not been explored. Consideration of surgical and radiation options may improve outcomes, and no studies have compared directly between the two localized treatment options. The development of new prognostic and predictive biomarkers may also enhance the treatment landscape in the future.
Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/terapia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Metástase Neoplásica , Imunoterapia , Terapia Combinada , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia , PrognósticoRESUMO
BACKGROUND: Although cardiovascular mortality has increased among middle-aged U.S. adults since 2011, how the burden of cardiovascular risk factors has changed for this population by income level over the past 2 decades is unknown. OBJECTIVE: To evaluate trends in the prevalence, treatment, and control of cardiovascular risk factors among low-income and higher-income middle-aged adults and how social determinants contribute to recent associations between income and cardiovascular health. DESIGN: Serial cross-sectional study. SETTING: NHANES (National Health and Nutrition Examination Survey), 1999 to March 2020. PARTICIPANTS: Middle-aged adults (aged 40 to 64 years). MEASUREMENTS: Age-standardized prevalence of hypertension, diabetes, hyperlipidemia, obesity, and cigarette use; treatment rates for hypertension, diabetes, and hyperlipidemia; and rates of blood pressure, glycemic, and cholesterol control. RESULTS: The study population included 20 761 middle-aged adults. The prevalence of hypertension, diabetes, and cigarette use was consistently higher among low-income adults between 1999 and March 2020. Low-income adults had an increase in hypertension over the study period (37.2% [95% CI, 33.5% to 40.9%] to 44.7% [CI, 39.8% to 49.5%]) but no changes in diabetes or obesity. In contrast, higher-income adults did not have a change in hypertension but had increases in diabetes (7.8% [CI, 5.0% to 10.6%] to 14.9% [CI, 12.4% to 17.3%]) and obesity (33.0% [CI, 26.7% to 39.4%] to 44.0% [CI, 40.2% to 47.7%]). Cigarette use was high and stagnant among low-income adults (33.2% [CI, 28.4% to 38.0%] to 33.9% [CI, 29.6% to 38.3%]) but decreased among their higher-income counterparts (18.6% [CI, 13.5% to 23.7%] to 11.5% [CI, 8.7% to 14.3%]). Treatment and control rates for hypertension were unchanged in both groups (>80%), whereas diabetes treatment rates improved only among the higher-income group (58.4% [CI, 44.4% to 72.5%] to 77.4% [CI, 67.6% to 87.1%]). Income-based disparities in hypertension, diabetes, and cigarette use persisted in more recent years even after adjustment for insurance coverage, health care access, and food insecurity. LIMITATION: Sample size limitations could preclude detection of small changes in treatment and control rates. CONCLUSION: Over 2 decades in the United States, hypertension increased in low-income middle-aged adults, whereas diabetes and obesity increased in their higher-income counterparts. Income-based disparities in hypertension, diabetes, and smoking persisted even after adjustment for other social determinants of health. PRIMARY FUNDING SOURCE: National Institutes of Health.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Hiperlipidemias , Hipertensão , Adulto , Pessoa de Meia-Idade , Humanos , Estados Unidos/epidemiologia , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Inquéritos Nutricionais , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Obesidade/epidemiologia , Prevalência , Hiperlipidemias/epidemiologia , Fatores de RiscoRESUMO
The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: Operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from deidentified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data are available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.
Assuntos
COVID-19/epidemiologia , Bases de Dados Factuais , Indicadores Básicos de Saúde , Assistência Ambulatorial/tendências , Métodos Epidemiológicos , Humanos , Internet/estatística & dados numéricos , Distanciamento Físico , Inquéritos e Questionários , Viagem , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Little cigars or cigarillos (LCCs) are frequently modified to smoke cannabis ("blunts") by youth and young adults. This study investigated whether young blunt users who are otherwise nicotine-naïve are more likely to initiate other tobacco products compared to never blunt users. METHODS AND MATERIALS: Data were from four waves of the Truth Longitudinal Cohort (TLC), a national probability-based sample of youth and young adults (aged 15-24 years) in the United States (Wave 1: January-April 2017; Wave 2: February-May 2018; Wave 3: February-May 2019; Wave 4: September-December 2019). The sample was restricted to nicotine naïve respondents at Wave 1 with possible ever use of blunts (N = 5,284). Logistic regression analyses tested whether ever blunt use at Wave 1 predicted initiation of nicotine products by Wave 4, controlling for established risk factors. RESULTS: Compared to never-blunt users, ever users of blunts at Wave 1 had significantly higher odds of ever using cigars (OR: 4.74; 95% CI: 1.80-12.47; p = 0.002), e-cigarettes (OR: 4.66; 95% CI: 2.42-8.95; p < 0.001), cigarettes (OR: 3.02; 95% CI: 1.17-7.84, p = 0.023), or hookah (OR: 3.47; 95% CI: 1.07-11.29, p = 0.039) by Wave 4. Cannabis (never blunt) use by Wave 1 predicted ever use of e-cigarettes (OR: 3.45, 95% CI: 2.38-5.02, p < 0.001), cigarettes (OR: 3.81; 95% CI: 2.26-6.43, p < 0.001), or hookah (OR: 2.13; 95% CI: 1.12-4.05, p = 0.021) by Wave 4. DISCUSSION: Blunts are a point of nicotine initiation that places users at increased risk of progression to cigars, while the same relationship was not found for cannabis alone.
Assuntos
Cannabis , Sistemas Eletrônicos de Liberação de Nicotina , Alucinógenos , Produtos do Tabaco , Humanos , Estados Unidos/epidemiologia , Adolescente , Adulto Jovem , Nicotina , Fatores de Risco , Uso de TabacoRESUMO
Importance: Medicare's Hospital Value-Based Purchasing (HVBP) program will provide a health equity adjustment (HEA) to hospitals that have greater proportions of patients dually eligible for Medicare and Medicaid and that offer high-quality care beginning in fiscal year 2026. However, which hospitals will benefit most from this policy change and to what extent are unknown. Objective: To estimate potential changes in hospital performance after HEA and examine hospital patient mix, structural, and geographic characteristics associated with receipt of increased payments. Design, Setting, and Participants: This cross-sectional study analyzed all 2676 hospitals participating in the HVBP program in fiscal year 2021. Publicly available data on program performance and hospital characteristics were linked to Medicare claims data on all inpatient stays for dual-eligible beneficiaries at each hospital to calculate HEA points and HVBP payment adjustments. Exposures: Hospital Value-Based Purchasing program HEA. Main Outcomes and Measures: Reclassification of HVBP bonus or penalty status and changes in payment adjustments across hospital characteristics. Results: Of 2676 hospitals participating in the HVBP program in fiscal year 2021, 1470 (54.9%) received bonuses and 1206 (45.1%) received penalties. After HEA, 102 hospitals (6.9%) were reclassified from bonus to penalty status, whereas 119 (9.9%) were reclassified from penalty to bonus status. At the hospital level, mean (SD) HVBP payment adjustments decreased by $4534 ($90â¯033) after HEA, ranging from a maximum reduction of $1â¯014â¯276 to a maximum increase of $1â¯523â¯765. At the aggregate level, net-positive changes in payment adjustments were largest among safety net hospitals ($28â¯971â¯708) and those caring for a higher proportion of Black patients ($15â¯468â¯445). The likelihood of experiencing increases in payment adjustments was significantly higher among safety net compared with non-safety net hospitals (574 of 683 [84.0%] vs 709 of 1993 [35.6%]; adjusted rate ratio [ARR], 2.04 [95% CI, 1.89-2.20]) and high-proportion Black hospitals compared with non-high-proportion Black hospitals (396 of 523 [75.7%] vs 887 of 2153 [41.2%]; ARR, 1.40 [95% CI, 1.29-1.51]). Rural hospitals (374 of 612 [61.1%] vs 909 of 2064 [44.0%]; ARR, 1.44 [95% CI, 1.30-1.58]), as well as those located in the South (598 of 1040 [57.5%] vs 192 of 439 [43.7%]; ARR, 1.25 [95% CI, 1.10-1.42]) and in Medicaid expansion states (801 of 1651 [48.5%] vs 482 of 1025 [47.0%]; ARR, 1.16 [95% CI, 1.06-1.28]), were also more likely to experience increased payment adjustments after HEA compared with their urban, Northeastern, and Medicaid nonexpansion state counterparts, respectively. Conclusions and Relevance: Medicare's implementation of HEA in the HVBP program will significantly reclassify hospital performance and redistribute program payments, with safety net and high-proportion Black hospitals benefiting most from this policy change. These findings suggest that HEA is an important strategy to ensure that value-based payment programs are more equitable.
Assuntos
Atenção à Saúde , Economia Hospitalar , Equidade em Saúde , Medicare , Aquisição Baseada em Valor , Humanos , Estudos Transversais , Grupos Diagnósticos Relacionados/economia , Grupos Diagnósticos Relacionados/estatística & dados numéricos , Elegibilidade Dupla ao MEDICAID e MEDICARE , Economia Hospitalar/estatística & dados numéricos , Equidade em Saúde/economia , Equidade em Saúde/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Medicare/economia , Medicare/estatística & dados numéricos , Qualidade da Assistência à Saúde/economia , Qualidade da Assistência à Saúde/estatística & dados numéricos , Estados Unidos/epidemiologia , Aquisição Baseada em Valor/economia , Aquisição Baseada em Valor/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Provedores de Redes de Segurança/economia , Provedores de Redes de Segurança/etnologia , Provedores de Redes de Segurança/estatística & dados numéricos , População Rural , Atenção à Saúde/economia , Atenção à Saúde/etnologia , Atenção à Saúde/estatística & dados numéricosRESUMO
OBJECTIVE: This report explores the experiences of preclinical medical students who led group dialectical behavior therapy (DBT) for a student-run LGBTQ + mental health clinic. METHODS: In the clinic, experienced clinicians trained and supervised preclinical medical students to facilitate DBT groups. The authors conducted a qualitative study to understand the impact of the DBT groups on the student facilitators via semi-structured interviews, which were evaluated using thematic analysis. RESULTS: The clinic hosted nine iterations of group DBT facilitated by preclinical medical students, involving 18 student leaders and 30 patients. Twelve student facilitators were interviewed. Participants had a diverse array of specialty interests and were primarily motivated by the opportunity for early clinical experience. They reported improved clinical skills, increased appreciation of psychotherapy as a treatment modality, and increased interest in incorporating psychotherapy in their future practice. Furthermore, participants reported using DBT skills to cultivate wellbeing during clerkship year and in their personal lives. CONCLUSIONS: Offering preclinical medical students the opportunity to lead group DBT therapy is a novel educational model providing early training in psychotherapy techniques. This opportunity for early direct patient experience in a supervised group setting attracted medical students with a diverse range of specialty interests. This model provided medical students specific DBT skills to implement in future patient care interactions and to maintain their personal wellbeing throughout medical training. The broad appeal and lasting effects of this program may prove beneficial at other institutions.
Assuntos
Terapia do Comportamento Dialético , Pesquisa Qualitativa , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Feminino , Masculino , Adulto , Clínica Dirigida por Estudantes , Educação de Graduação em Medicina , Serviços de Saúde Mental , Minorias Sexuais e de Gênero , Psicoterapia de Grupo/educação , Estágio ClínicoRESUMO
PURPOSE: Perioperative vision loss (POVL) is a rare and devastating complication following prone spine surgery. Due to the rare nature of this complication, there is limited research available about patient and surgical risk factors that increase the risk of POVL. The objective of this study was to investigate associated risk factors for POVL with use of the National Surgical Quality Improvement Program (NSQIP) database. DESIGN: This study used a case-control secondary data analysis methodology that included five cases of POVL and 250 controls from the American College of Surgeons National Surgical Quality Improvement Program database who all underwent prone spine surgery between 2010 and 2020. METHODS: Each POVL case was matched to 50 randomly selected controls (n = 250) based on type and year of surgery. Demographics and variables of interest were compared among the POVL cases, among POVL cases and the aggregate control group (n = 250), and POVL cases against their matched control group. Univariate and multivariate conditional logistic regression were then used to estimate the odds of developing POVL in relation to potential patient and surgical risk factors. FINDINGS: When POVL cases were compared to the 250 control cases using univariate analysis, patients who developed POVL were more likely to have received a blood transfusion within 72 hours of surgery (P < .0001). and have longer operative times (odds ratio = 1.01, 95% CI [1.003, 1.017], P = .003). CONCLUSIONS: Two surgical risk factors were determined to be statistically significant, including the need for perioperative blood transfusion and prolonged operative time. These findings support previous research on POVL which often identified blood loss and prolonged operative times as surgical risk factors. The narrow patient population used in this project may have limited the ability to perform a more robust study on POVL. Therefore, further research on POVL using the National Surgical Quality Improvement Program database is strongly encouraged.
RESUMO
Obstructive sleep apnea (OSA) is a common condition that can cause daytime or nocturnal symptoms with long-term impact on the patient's health. Various therapies and surgeries have been introduced over the years, and patient wishes and compliance are essential factors in the success of treatment. Drug-induced sleep endoscopy (DISE) is a procedure that assesses the opening and closing of the upper airway in real time. This article summarizes the indications and contraindications of DISE, with a review of sedation methods and the VOTE classification system, in order to facilitate the use of a common nomenclature based on a protocol applied at the CHUV.
Le syndrome d'apnées obstructives du sommeil (SAOS) est une affection courante pouvant provoquer des symptômes diurnes ou nocturnes ayant un impact à long terme sur la santé du patient. Diverses thérapies et chirurgies ont été introduites au fil des années et les souhaits des patients et l'observance thérapeutique sont des facteurs essentiels dans le succès du traitement. L'endoscopie du sommeil induit par les médicaments (DISE: drug-induced sleep endoscopy) permet d'évaluer l'ouverture et la fermeture des voies respiratoires supérieures en temps réel. Cet article résume les indications et contre-indications de la DISE avec un rappel des méthodes de sédation et le système de classification VOTE, afin de faciliter l'utilisation d'une nomenclature commune basée sur un protocole appliqué au CHUV.
Assuntos
Anestesia , Laringe , Humanos , Endoscopia , Contraindicações , SonoRESUMO
PURPOSE: Currently, there are multiple active clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of glioblastoma. The noninvasive quantification of baseline PARP expression using positron emission tomography (PET) may provide prognostic information and lead to more precise treatment. Due to the lack of brain-penetrant PARP imaging agents, the reliable and accurate in vivo quantification of PARP in the brain remains elusive. Herein, we report the synthesis of a brain-penetrant PARP PET tracer, (R)-2-(2-methyl-1-(methyl-11C)pyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide ([11C]PyBic), and its preclinical evaluations in a syngeneic RG2 rat glioblastoma model and healthy nonhuman primates. METHODS: We synthesized [11C]PyBic using veliparib as the labeling precursor, performed dynamic PET scans on RG2 tumor-bearing rats and calculated the distribution volume ratio (DVR) using simplified reference region method 2 (SRTM2) with the contralateral nontumor brain region as the reference region. We performed biodistribution studies, western blot, and immunostaining studies to validate the in vivo PET quantification results. We characterized the brain kinetics and binding specificity of [11C]PyBic in nonhuman primates on FOCUS220 scanner and calculated the volume of distribution (VT), nondisplaceable volume of distribution (VND), and nondisplaceable binding potential (BPND) in selected brain regions. RESULTS: [11C]PyBic was synthesized efficiently in one step, with greater than 97% radiochemical and chemical purity and molar activity of 148 ± 85 MBq/nmol (n = 6). [11C]PyBic demonstrated PARP-specific binding in RG2 tumors, with 74% of tracer binding in tumors blocked by preinjected veliparib (i.v., 5 mg/kg). The in vivo PET imaging results were corroborated by ex vivo biodistribution, PARP1 immunohistochemistry and immunoblotting data. Furthermore, brain penetration of [11C]PyBic was confirmed by quantitative monkey brain PET, which showed high specific uptake (BPND > 3) and low nonspecific uptake (VND < 3 mL/cm3) in the monkey brain. CONCLUSION: [11C]PyBic is the first brain-penetrant PARP PET tracer validated in a rat glioblastoma model and healthy nonhuman primates. The brain kinetics of [11C]PyBic are suitable for noninvasive quantification of available PARP binding in the brain, which posits [11C]PyBic to have broad applications in oncology and neuroimaging.
Assuntos
Glioblastoma , Ratos , Animais , Glioblastoma/diagnóstico por imagem , Glioblastoma/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/metabolismo , Distribuição Tecidual , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , PrimatasRESUMO
Objectives. To assess the performance of US federally qualified health centers (FQHCs) after 6 years of required sexual orientation and gender identity (SOGI) data reporting and update estimated proportions of sexual and gender minorities cared for at FQHCs. Methods. We conducted secondary analyses of data reported to the 2020 and 2021 Uniform Data System from 1297 FQHCs caring for nearly 30 000 000 patients annually. We used multivariable logistic regression to explore FQHC-level and patient-level factors associated with SOGI data completeness. Results. SOGI data were missing for 29.1% and 24.0% of patients, respectively. Among patients with reported SOGI data, 3.5% identified as sexual minorities and 1.5% identified as gender minorities. Southern FQHCs and those caring for more low-income and Black patients were more likely to have above-average SOGI data completeness. Larger FQHCs were more likely to have below-average SOGI data completeness. Conclusions. Substantial increases in SOGI data completeness at FQHCs over 6 years reflect the success of reporting mandates. Future research is needed to identify other patient-level and FQHC-level factors contributing to residual levels of SOGI data missingness. (Am J Public Health. 2023;113(8):883-892. https://doi.org/10.2105/AJPH.2023.307323).
Assuntos
Identidade de Gênero , Minorias Sexuais e de Gênero , Humanos , Feminino , Masculino , Comportamento SexualRESUMO
BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.
Assuntos
Algoritmos , Biomarcadores/sangue , Infarto do Miocárdio/diagnóstico , Guias de Prática Clínica como Assunto , Triagem/métodos , Troponina/sangue , Diagnóstico Diferencial , Europa (Continente) , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Sociedades Médicas , Fatores de TempoRESUMO
BACKGROUND: Cardiovascular deaths increased during the early phase of the COVID-19 pandemic in the United States. However, it is unclear whether diverse racial/ethnic populations have experienced a disproportionate rise in heart disease and cerebrovascular disease deaths. METHODS: We used the National Center for Health Statistics to identify heart disease and cerebrovascular disease deaths for non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic individuals from March to August 2020 (pandemic period), as well as for the corresponding months in 2019 (historical control). We determined the age- and sex-standardized deaths per million by race/ethnicity for each year. We then fit a modified Poisson model with robust SEs to compare change in deaths by race/ethnicity for each condition in 2020 versus 2019. RESULTS: There were a total of 339 076 heart disease and 76 767 cerebrovascular disease deaths from March through August 2020, compared with 321 218 and 72 190 deaths during the same months in 2019. Heart disease deaths increased during the pandemic in 2020, compared with the corresponding period in 2019, for non-Hispanic White (age-sex standardized deaths per million, 1234.2 versus 1208.7; risk ratio for death [RR], 1.02 [95% CI, 1.02-1.03]), non-Hispanic Black (1783.7 versus 1503.8; RR, 1.19 [95% CI, 1.17-1.20]), non-Hispanic Asian (685.7 versus 577.4; RR, 1.19 [95% CI, 1.15-1.22]), and Hispanic (968.5 versus 820.4; RR, 1.18 [95% CI, 1.16-1.20]) populations. Cerebrovascular disease deaths also increased for non-Hispanic White (268.7 versus 258.2; RR, 1.04 [95% CI, 1.03-1.05]), non-Hispanic Black (430.7 versus 379.7; RR, 1.13 [95% CI, 1.10-1.17]), non-Hispanic Asian (236.5 versus 207.4; RR, 1.15 [95% CI, 1.09-1.21]), and Hispanic (264.4 versus 235.9; RR, 1.12 [95% CI, 1.08-1.16]) populations. For both heart disease and cerebrovascular disease deaths, Black, Asian, and Hispanic populations experienced a larger relative increase in deaths than the non-Hispanic White population (interaction term, P<0.001). CONCLUSIONS: During the COVID-19 pandemic in the United States, Black, Hispanic, and Asian populations experienced a disproportionate rise in deaths caused by heart disease and cerebrovascular disease, suggesting that these groups have been most impacted by the indirect effects of the pandemic. Public health and policy strategies are needed to mitigate the short- and long-term adverse effects of the pandemic on the cardiovascular health of diverse populations.
Assuntos
COVID-19/patologia , Transtornos Cerebrovasculares/mortalidade , Disparidades nos Níveis de Saúde , Cardiopatias/mortalidade , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Asiático/estatística & dados numéricos , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/virologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/etnologia , Transtornos Cerebrovasculares/patologia , Feminino , Cardiopatias/complicações , Cardiopatias/etnologia , Hispânico ou Latino/estatística & dados numéricos , Mortalidade Hospitalar/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Risco , SARS-CoV-2/isolamento & purificação , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. OBJECTIVE: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. METHODS: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. RESULTS: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. CONCLUSION: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Infecções por HIV , Inibidores de Hidroximetilglutaril-CoA Redutases , Doença Arterial Periférica , Veteranos , Idoso , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/tratamento farmacológico , PrescriçõesRESUMO
BACKGROUND: Hospitalizations fell precipitously among the general population during the COVID-19 pandemic. It remains unclear whether individuals experiencing homelessness experienced similar reductions. OBJECTIVE: To examine how overall and cause-specific hospitalizations changed among individuals with a recent history of homelessness (IRHH) and their housed counterparts during the first wave of the COVID-19 pandemic, using corresponding weeks in 2019 as a historical control. DESIGN: Population-based cohort study conducted in Ontario, Canada, between September 30, 2018, and September 26, 2020. PARTICIPANTS: In total, 38,617 IRHH, 15,022,368 housed individuals, and 186,858 low-income housed individuals matched on age, sex, rurality, and comorbidity burden. MAIN MEASURES: Primary outcomes included medical-surgical, non-elective (overall and cause-specific), elective surgical, and psychiatric hospital admissions. KEY RESULTS: Average rates of medical-surgical (rate ratio: 3.8, 95% CI: 3.7-3.8), non-elective (10.3, 95% CI: 10.1-10.4), and psychiatric admissions (128.1, 95% CI: 126.1-130.1) between January and September 2020 were substantially higher among IRHH compared to housed individuals. During the peak period (March 17 to June 16, 2020), rates of medical-surgical (0.47, 95% CI: 0.47-0.47), non-elective (0.80, 95% CI: 0.79-0.80), and psychiatric admissions (0.86, 95% CI: 0.84-0.88) were significantly lower among housed individuals relative to equivalent weeks in 2019. No significant changes were observed among IRHH. During the re-opening period (June 17-September 26, 2020), rates of non-elective hospitalizations for liver disease (1.41, 95% CI: 1.23-1.69), kidney disease (1.29, 95% CI: 1.14-1.47), and trauma (1.19, 95% CI: 1.07-1.32) increased substantially among IRHH but not housed individuals. Distinct hospitalization patterns were observed among IRHH even in comparison with more medically and socially vulnerable matched housed individuals. CONCLUSIONS: Persistence in overall hospital admissions and increases in non-elective hospitalizations for liver disease, kidney disease, and trauma indicate that the COVID-19 pandemic presented unique challenges for recently homeless individuals. Health systems must better address the needs of this population during public health crises.