RESUMO
We provide updated results (11 October 2023 through 29 February 2024) from our previously conducted test-negative case-control study in Kaiser Permanente Southern California to evaluate sublineage-specific effectiveness of the BNT162b2 XBB1.5-adapted vaccine. Results suggest that XBB1.5-adapted vaccines may have reduced effectiveness against JN.1 versus XBB sublineages.
RESUMO
Importance: Data describing the early additional protection afforded by the recently recommended BNT162b2 XBB vaccine (Pfizer-BioNTech; 2023-2024 formulation) are limited. Objective: To estimate the association between receipt of the BNT162b2 XBB vaccine and medically attended COVID-19 outcomes among US adults 18 years and older. Design, Setting, and Participants: This test-negative case-control study was performed to estimate the effectiveness of the BNT162b2 XBB vaccine against COVID-19-associated hospitalization and emergency department (ED) or urgent care (UC) encounters among adults in the Kaiser Permanente Southern California health system between October 10, 2023, and December 10, 2023. Cases were those presenting with an acute respiratory illness and who had a positive SARS-CoV-2 polymerase chain reaction test; controls had an acute respiratory illness but tested negative for SARS-CoV-2. Exposure: The primary exposure was receipt of the BNT162b2 XBB vaccine compared with not receiving an XBB vaccine of any kind, regardless of prior COVID-19 vaccination or SARS-CoV-2 infection history. Receipt of prior (non-XBB) versions of COVID-19 vaccines was also compared with being unvaccinated to estimate remaining protection from older vaccines. Main Outcomes and Measures: Analyses for cases and controls were conducted separately for COVID-19 hospital admissions and ED/UC encounters. Adjusted odds ratios and 95% CIs were estimated from multivariable logistic regression models that were adjusted for patient demographic and clinical characteristics. Estimation of vaccine effectiveness was calculated as 1 - odds ratio × 100%. Results: Among 2854 cases and 15â¯345 controls (median [IQR] age, 56 [37-72] years; 10â¯658 [58.6%] female), adjusted estimation of effectiveness of the BNT162b2 XBB vaccine received a median of 34 days prior vs not having received an XBB vaccine of any kind was 62% (95% CI, 32%-79%) against COVID-19 hospitalization and 58% (95% CI, 48%-67%) for ED/UC visits. Compared with being unvaccinated, those who had received only older versions of COVID-19 vaccines did not show statistically significant reduced risk of COVID-19 outcomes, including hospital admission. Conclusions and Relevance: Findings of this case-control study reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines given that (1) the BNT162b2 XBB vaccine provided statistically significant additional protection against a range of COVID-19 outcomes and (2) older versions of COVID-19 vaccines offered little, if any, long-term protection, including against hospital admission, regardless of the number or type of prior doses received.
Assuntos
Vacina BNT162 , COVID-19 , Hospitalização , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacina BNT162/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Adulto , Hospitalização/estatística & dados numéricos , SARS-CoV-2/imunologia , Eficácia de Vacinas , Vacinas contra COVID-19/administração & dosagem , California/epidemiologiaRESUMO
Background: Sublingual immunotherapy (SLIT) with 12 SQ house dust mile SLIT-tablet (HDM SLIT-tablet) for dust mite-induced perennial allergic rhinitis is reported as effective and safe. Although serious allergic reactions (SARs) and eosinophilic esophagitis (EoE) have infrequently occurred under trial conditions, the safety of HDM SLIT-tablet challenge under real-world conditions is unknown. Objective: Our aim was to estimate the incidence of SARs and EoE due to HDM SLIT-tablet challenge. Methods: Through use of administrative data from Kaiser Permanente Southern California, this prospective observational study identified patients newly administered HDM SLIT-tablet with follow-up until SLIT discontinuation or end of study. Suspected cases of SARs and EoE were detected by using International Classification of Diseases, 10th Revision, diagnosis and Current Procedural Terminology procedure codes and medication dispensing records. A 3-member clinical review committee of allergists adjudicated suspected reactions. The incidence rate of confirmed SARs and EoE per 1000 person years of exposure were determined. Results: A total of 521 patients (93.9% adult and 6.1% pediatric) were exposed to HDM SLIT-tablet challenge from January 2018 through May 2023, for 440.4 person years of exposure. The patients' average age (SD) was 39.3 (14.1) years, 58.7% were female, 44.3% were non-Hispanic White, 40.3% had asthma, and 15.0% had gastroesophageal reflux disease. A SAR occurred in 1 adult patient, and during initial HDM SLIT-tablet challenge, SARs occurred in 2 pediatric adolescents, for an overall incidence of 6.8 SARs per 1000 patient years (95% CI = 2.2-21.1). EoE occurred in 1 adult patient, for an overall incidence of 2.3 cases of EoE per 1000 patient years (95% CI = 0.3-16.1). Conclusions: This real-world study demonstrated that SARs and EoE were infrequent events with HDM SLIT-tablet use, supporting the safety of HDM SLIT-tablets and need for physician supervision with initial challenge.
RESUMO
BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.
Assuntos
Poluição do Ar , Hipertensão Induzida pela Gravidez , Material Particulado , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Material Particulado/efeitos adversos , Material Particulado/análise , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/etiologia , Adulto , Poluição do Ar/efeitos adversos , California/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Adulto Jovem , Exposição Materna/efeitos adversos , Fatores de Risco , Exposição Ambiental/efeitos adversosRESUMO
A clear understanding of real-world uptake of nirmatrelvir-ritonavir for treatment of SARS-CoV-2 can inform treatment allocation strategies and improve interpretation of effectiveness studies. We used data from a large US healthcare system to describe nirmatrelvir-ritonavir dispenses among all SARS-CoV-2 positive patients aged ≥ 12 years meeting recommended National Institutes of Health treatment eligibility criteria for the study period between 1 January and 31 December, 2022. Overall, 10.9% (N = 34,791/319,900) of treatment eligible patients with SARS-CoV-2 infections received nirmatrelvir-ritonavir over the study period. Although uptake of nirmatrelvir-ritonavir increased over time, by the end of 2022, less than a quarter of treatment eligible patients with SARS-CoV-2 infections had received nirmatrelvir-ritonavir. Across patient demographics, treatment was generally consistent with tiered treatment guidelines, with dispenses concentrated among patients aged ≥ 65 years (14,706/63,921; 23.0%), and with multiple comorbidities (10,989/54,431; 20.1%). However, neighborhoods of lower socioeconomic status (upper third of neighborhood deprivation index [NDI]) had between 12% (95% CI: 7-18%) and 28% (25-32%) lower odds of treatment dispense over the time periods studied compared to the lower third of NDI distribution, even after accounting for demographic and clinical characteristics. A limited chart review (N = 40) confirmed that in some cases a decision not to treat was appropriate and aligned with national guidelines to use clinical judgement on a case-by-case basis. There is a need to enhance patient and provider awareness on the availability and benefits of nirmatrelvir-ritonavir for the treatment of COVID-19 illness.
Assuntos
COVID-19 , Lactamas , Leucina , Nitrilas , Prolina , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Ritonavir/uso terapêutico , Tratamento Farmacológico da COVID-19 , Antivirais/uso terapêuticoRESUMO
Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.
Assuntos
Metilação de DNA , Neoplasias da Próstata , Masculino , Humanos , Estudos de Casos e Controles , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de RiscoRESUMO
BACKGROUND: XBB-related omicron sublineages have recently replaced BA.4/5 as the predominant omicron sublineages in the USA and other regions globally. Despite preliminary signs of immune evasion of XBB sublineages, few data exist describing the real-world effectiveness of bivalent COVID-19 vaccines, especially against XBB-related illness. We aimed to investigate the effectiveness of the Pfizer--BioNTech BNT162b2 BA.4/5 bivalent vaccine against both BA.4/5-related and XBB-related disease in adults aged 18 years or older. METHODS: In this test-negative case-control study, we estimated the effectiveness of the BNT162b2 BA.4/5 bivalent vaccine using data from electronic health records of Kaiser Permanente Southern California health system members aged 18 years or older who received at least two doses of the wild-type COVID-19 mRNA vaccines. Participants sought care for acute respiratory infection between Aug 31, 2022, and April 15, 2023, and were tested for SARS-CoV-2 via PCR tests. Relative vaccine effectiveness (≥2 doses of wild-type mRNA vaccine plus a BNT162b2 BA.4/5 bivalent booster vs ≥2 doses of a wild-type mRNA vaccine alone) and absolute vaccine effectiveness (vs unvaccinated individuals) was estimated against critical illness related to acute respiratory infection (intensive care unit [ICU] admission, mechanical ventilation, or inpatient death), hospital admission, emergency department or urgent care visits, and in-person outpatient encounters with odds ratios from logistic regression models adjusted for demographic and clinical factors. We stratified vaccine effectiveness estimates for hospital admission, emergency department or urgent care visits, and outpatient encounters by omicron sublineage (ie, likely BA.4/5-related vs likely XBB-related), time since bivalent booster receipt, age group, number of wild-type doses received, and immunocompromised status. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were conducted for 123 419 encounters (24 246 COVID-19 cases and 99 173 test-negative controls), including 4131 episode of critical illness (a subset of hospital admissions), 14 529 hospital admissions, 63 566 emergency department or urgent care visits, and 45 324 outpatient visits. 20 555 infections were BA.4/5 related and 3691 were XBB related. In adjusted analyses, relative vaccine effectiveness for those who received the BNT162b2 BA.4/5 bivalent booster compared with those who received at least two doses of a wild-type mRNA vaccine alone was an additional 50% (95% CI 23-68) against critical illness, an additional 39% (28-49) against hospital admission, an additional 35% (30-40) against emergency department or urgent care visits, and an additional 28% (22-33) against outpatient encounters. Waning of the bivalent booster from 0-3 months to 4-7 months after vaccination was evident for outpatient outcomes but was not detected for critical illness, hospital admission, and emergency department or urgent care outcomes. The relative effectiveness of the BNT162b2 BA.4/5 bivalent booster for XBB-related infections compared with BA.4/5-related infections was 56% (95% CI 12-78) versus 40% (27-50) for hospital admission; 34% (21-45) versus 36% (30-41) against emergency department or urgent care visits; and 29% (19-38) versus 27% (20-33) for outpatient encounters. INTERPRETATION: By mid-April, 2023, individuals previously vaccinated only with wild-type vaccines had little protection against COVID-19-including hospital admission. A BNT162b2 BA.4/5 bivalent booster restored protection against a range of COVID-19 outcomes, including against XBB-related sublineages, with the most substantial protection observed against hospital admission and critical illness. FUNDING: Pfizer.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Estados Unidos/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacina BNT162 , SARS-CoV-2 , Estudos de Casos e Controles , Estado Terminal , Vacinas de mRNA , Vacinas CombinadasRESUMO
Importance: Women are especially vulnerable to mental health matters post partum because of biological, emotional, and social changes during this period. However, epidemiologic evidence of an association between air pollution exposure and postpartum depression (PPD) is limited. Objective: To examine the associations between antepartum and postpartum maternal air pollution exposure and PPD. Design, Setting, and Participants: This retrospective cohort study used data from Kaiser Permanente Southern California (KPSC) electronic health records and included women who had singleton live births at KPSC facilities between January 1, 2008, and December 31, 2016. Data were analyzed between January 1 and May 10, 2023. Exposures: Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter less than or equal to 2.5 µm (PM2.5), particulate matter less than or equal to 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) from spatial interpolation of monitoring station measurements. Constituents of PM2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from fine-resolution geoscience-derived models based on satellite, ground-based monitor, and chemical transport modeling data. Main Outcomes and Measures: Participants with an Edinburgh Postnatal Depression Scale score of 10 or higher during the 6 months after giving birth were referred to a clinical interview for further assessment and diagnosis. Ascertainment of PPD was defined using a combination of diagnostic codes and prescription medications. Results: The study included 340â¯679 participants (mean [SD] age, 30.05 [5.81] years), with 25â¯674 having PPD (7.54%). Increased risks for PPD were observed to be associated with per-IQR increases in antepartum and postpartum exposures to O3 (adjusted odds ratio [AOR], 1.09; 95% CI, 1.06-1.12), PM10 (AOR, 1.02; 95% CI, 1.00-1.04), and PM2.5 (AOR, 1.02; 95% CI, 1. 00-1.03) but not with NO2; PPD risks were mainly associated with PM2.5 organic matter and black carbon. Overall, a higher risk of PPD was associated with O3 during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods. Conclusions and Relevance: The study findings suggest that long-term exposure to antepartum and postpartum air pollution was associated with higher PPD risks. Identifying the modifiable environmental risk factors and developing interventions are important public health issues to improve maternal mental health and alleviate the disease burden of PPD.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Depressão Pós-Parto , Ozônio , Gravidez , Humanos , Feminino , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Exposição Ambiental/efeitos adversos , Estudos Retrospectivos , Dióxido de Nitrogênio , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Período Pós-Parto , CarbonoRESUMO
This study examines the association of the receipt of wild-type BNT162b2 vaccine with medically attended COVID-19 outcomes among children younger than 5 years in the US.
Assuntos
Vacina BNT162 , COVID-19 , Humanos , Vacina BNT162/uso terapêutico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Assistência Ambulatorial/estatística & dados numéricos , Estados Unidos/epidemiologia , Pré-Escolar , Vacinação/estatística & dados numéricos , Fatores EtáriosRESUMO
PURPOSE: Weight loss surgery is an effective, long-term treatment for severe obesity but individual response to surgery varies widely. The purpose of this study was to test a comprehensive theoretical model of factors that may be correlated with the greatest surgical weight loss at 1-3 years following surgery. Such a model would help determine what predictive factors to measure when patients are preparing for surgery that may ensure the best weight outcomes. MATERIALS AND METHODS: The Bariatric Experience Long Term (BELONG) study collected self-reported and medical record-based baseline information as correlates of 1- and 3-year % total weight loss (TWL) in n = 1341 patients. Multiple linear regression was used to determine the associations between 120 baseline variables and %TWL. RESULTS: Participants were 43.4 ± 11.3 years old, Hispanic or Black (52%; n = 699), women (86%; n = 1149), and partnered (72%; n = 965) and had annual incomes of ≥ $51,000 (60%; n = 803). A total of 1006 (75%) had 3-year follow-up weight. Regression models accounted for 10.1% of the variance in %TWL at 1-year and 13.6% at 3 years. Only bariatric operation accounted for a clinically meaningful difference (~ 5%) in %TWL at 1-year. At 3 years after surgery, only bariatric operation, Black race, and BMI ≥ 50 kg/m2 were associated with clinically meaningful differences in %TWL. CONCLUSIONS: Our findings combined with many others support a move away from extensive screening and selection of patients at the time of surgery to a focus on improving access to this treatment.
Assuntos
Cirurgia Bariátrica , Bariatria , Obesidade Mórbida , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Hispânico ou Latino , Obesidade Mórbida/cirurgia , Redução de Peso , Negro ou Afro-Americano , MasculinoRESUMO
Importance: Immunocompromised individuals are at increased risk for severe outcomes due to SARS-CoV-2 infection. Given the varying and complex nature of COVID-19 vaccination recommendations, it is important to understand COVID-19 vaccine uptake in this vulnerable population. Objective: To assess mRNA COVID-19 vaccine uptake and factors associated with uptake among immunocompromised individuals from December 14, 2020, through August 6, 2022. Design, Setting, and Participants: This cohort study was conducted with patients of Kaiser Permanente Southern California (KPSC), an integrated health care system in the US. The study included patients aged 18 years or older who were immunocompromised (individuals with an immunocompromising condition or patients who received immunosuppressive medications in the year prior to December 14, 2020) and still met criteria for being immunocompromised 1 year later. Exposures: Age, sex, self-identified race and ethnicity, prior positive COVID-19 test result, immunocompromising condition, immunomodulating medication, comorbidities, health care utilization, and neighborhood median income. Main Outcomes and Measures: Outcomes were the number of doses of mRNA COVID-19 vaccine received and the factors associated with receipt of at least 4 doses, estimated by hazard ratios (HRs) and 95% Wald CIs via Cox proportional hazards regression. Statistical analyses were conducted between August 9 and 23, 2022. Results: Overall, 42â¯697 immunocompromised individuals met the study eligibility criteria. Among these, 18â¯789 (44.0%) were aged 65 years or older; 20 061 (47.0%) were women and 22 635 (53.0%) were men. With regard to race and ethnicity, 4295 participants (10.1%) identified as Asian or Pacific Islander, 5174 (12.1%) as Black, 14â¯289 (33.5%) as Hispanic, and 17â¯902 (41.9%) as White. As of the end of the study period and after accounting for participant censoring due to death or disenrollment from the KPSC health plan, 78.0% of immunocompromised individuals had received a third dose of mRNA COVID-19 vaccine. Only 41.0% had received a fourth dose, which corresponds to a primary series and a monovalent booster dose for immunocompromised individuals. Uptake of a fifth dose was only 0.9% following the US Centers for Disease Control and Prevention (CDC) recommendation to receive a second monovalent booster (ie, fifth dose). Adults aged 65 years or older (HR, 3.95 [95% CI, 3.70-4.22]) were more likely to receive at least 4 doses compared with those aged 18 to 44 years or 45 to 64 years (2.52 [2.36-2.69]). Hispanic and non-Hispanic Black adults (HR, 0.77 [95% CI, 0.74-0.80] and 0.82 [0.78-0.87], respectively, compared with non-Hispanic White adults), individuals with prior documented SARS-CoV-2 infection (0.71 [0.62-0.81] compared with those without), and individuals receiving high-dose corticosteroids (0.88 [0.81-0.95] compared with those who were not) were less likely to receive at least 4 doses. Conclusions and Relevance: These findings suggest that adherence to CDC mRNA monovalent COVID-19 booster dose recommendations among immunocompromised individuals was low. Given the increased risk for severe COVID-19 in this vulnerable population and the well-established additional protection afforded by booster doses, targeted and tailored efforts to ensure that immunocompromised individuals remain up to date with COVID-19 booster dose recommendations are warranted.
Assuntos
COVID-19 , Estados Unidos/epidemiologia , Adulto , Masculino , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Coortes , SARS-CoV-2 , EtnicidadeRESUMO
In a 1:1 matched test-negative design among 5- to 11-year-olds in the Kaiser Permanente Southern California health system (n = 3984), BNT162b2 effectiveness against the omicron-related emergency department or urgent care encounters was 60% [95%CI: 47-69] <3 months post-dose-two and 28% [8-43] after ≥3 months. A booster improved protection to 77% [53-88].
Assuntos
Vacina BNT162 , COVID-19 , Humanos , Criança , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: The SARS-CoV-2 omicron (B.1.1.529 BA.1) lineage was first detected in November, 2021, and is associated with reduced vaccine effectiveness. By March, 2022, BA.1 had been replaced by sub-lineage BA.2 in the USA. As new variants evolve, vaccine performance must be continually assessed. We aimed to evaluate the effectiveness and durability of BNT162b2 (Pfizer-BioNTech) against hospital and emergency department admissions for BA.1 and BA.2. METHODS: In this test-negative, case-control study, we sourced data from the electronic health records of adult (aged ≥18 years) members of Kaiser Permanente Southern California (KPSC), which is a health-care system in the USA, who were admitted to one of 15 KPSC hospitals or emergency departments (without subsequent hospitalisation) between Dec 27, 2021, and June 4, 2022, with an acute respiratory infection and were tested for SARS-CoV-2 by RT-PCR. Omicron sub-lineage was determined by use of sequencing, spike gene target failure, and the predominance of variants in certain time periods. Our main outcome was the effectiveness of two or three doses of BNT162b2 in preventing emergency department or hospital admission. Variant-specific vaccine effectiveness was evaluated by comparing the odds ratios from logistic regression models of vaccination between test-positive cases and test-negative controls, adjusting for the month of admission, age, sex, race and ethnicity, body-mass index, Charlson Comorbidity Index, previous influenza or pneumococcal vaccines, and previous SARS-CoV-2 infection. We also assessed effectiveness by the time since vaccination. This study is registered at ClinicalTrials.gov, NCT04848584, and is ongoing. FINDINGS: Of 65 813 total admissions during the study period, we included 16 994 in our analyses, of which 7435 were due to BA.1, 1056 were due to BA.2, and 8503 were not due to SARS-CoV-2. In adjusted analyses, two-dose vaccine effectiveness was 40% (95% CI 27 to 50) for hospitalisation and 29% (18 to 38) for emergency department admission against BA.1 and 56% (31 to 72) for hospitalisation and 16% (-5 to 33) for emergency department admission against BA.2. Three-dose vaccine effectiveness was 79% (74 to 83) for hospitalisation and 72% (67 to 77) for emergency department admission against BA.1 and 71% (55 to 81) for hospitalisation and 21% (1 to 37) for emergency department admission against BA.2. Less than 3 months after the third dose, vaccine effectiveness was 80% (74 to 84) for hospitalisation and 74% (69 to 78) for emergency department admission against BA.1. Vaccine effectiveness 3 months or more after the third dose was 76% (69 to 82) against BA.1-related hospitalisation and 65% (56 to 73) against BA.1-related emergency department admission. Against BA.2, vaccine effectiveness was 74% (47 to 87) for hospitalisation and 59% (40 to 72) for emergency department admission at less than 3 months after the third dose and 70% (53 to 81) for hospitalisation and 5% (-21 to 25) for emergency department admission at 3 months or more after the third dose. INTERPRETATION: Two doses of BNT162b2 provided only partial protection against BA.1-related and BA.2-related hospital and emergency department admission, which underscores the need for booster doses against omicron. Although three doses offered high levels of protection (≥70%) against hospitalisation, variant-adapted vaccines are probably needed to improve protection against less severe endpoints, like emergency department admission, especially for BA.2. FUNDING: Pfizer.
Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Adolescente , Vacina BNT162 , Estudos de Casos e Controles , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hospitalização , Hospitais , Vacinas Pneumocócicas , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: Few studies have evaluated the effect of statin exposure on metastasis risk among prostate cancer patients not receiving curative treatment. METHODS: We included men diagnosed with localized prostate cancer at an integrated health care system between 1997 and 2006 who did not receive curative treatment within 6 months of diagnosis. We followed these men until a metastatic event, disenrollment, death, or 12/31/2016. We collected all data from electronic health records supplemented by chart review. We used Cox regressions to examine the association between post-diagnostic statin exposure and metastasis, controlling for clinical characteristics and pre-diagnostic statin exposure. RESULTS: There were 4245 men included. Mean age of diagnosis was 68.02 years. 46.6% of men used statins after prostate cancer diagnosis. During follow-up, 192 men developed metastasis (cumulative incidence rate: 14.5%). In the adjusted Cox model, statin use post-prostate cancer diagnosis was not significantly associated with a metastatic event (HR = 0.97, 95% CI = 0.69, 1.36). Pre-diagnostic statin use was also not associated with development of metastasis (HR = 0.76, 95% CI = 0.53, 1.10). We did not observe a dose-response for the proportion of person-time at-risk post-prostate cancer diagnosis on statins (HR = 0.98 per 10% increase in person-time exposed [95% CI = 0.93, 1.03]). CONCLUSIONS: We did not find an inverse association between post-diagnosis statin exposure and metastasis development in localized prostate cancer patients who did not receive active treatment. Our results did not offer support to the chemopreventive potential of post-diagnostic statin use among men on active surveillance.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias da Próstata , Masculino , Humanos , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Seguimentos , Progressão da Doença , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Próstata/patologiaRESUMO
Importance: Data about the duration of protection of 2 and 3 doses of BNT162b2 in children and adolescents are needed to help inform recommendations for boosters in this age group. Objective: To evaluate vaccine effectiveness (VE) and durability associated with 2 doses of BNT162b2 against Delta- and Omicron-related emergency department (ED) and urgent care (UC) encounters among adolescents aged 12 to 17 years and to estimate VE associated with 3 doses against these same outcomes. Design, Setting, and Participants: This test-negative case-control study was conducted at Kaiser Permanente Southern California, an integrated health care system using electronic health records in the US. Participants included Kaiser Permanente Southern California members ages 12 to 17 years with an ED or UC encounter from November 1, 2021, through March 18, 2022, for acute respiratory infection who were tested for SARS-CoV-2 via a reverse transction-polymerase chain reaction test. Analyses were conducted from March 21 to June 22, 2022. Exposures: BNT162b2 vaccination status ascertained from electronic health records and state registry data. Main Outcomes and Measures: The main outcome was VE associated with BNT162b2 against ED and UC encounters related to Delta or Omicron variant SARS-CoV-2 infection. Results: Analyses were conducted among 3168 adolescents, including 1004 with ED visits and 2164 with UC visits. Median (IQR) age was 15 (13-16) years, and 1461 (46.1%) were boys. In adjusted analyses, VE associated with 2 doses of BNT162b2 against ED or UC encounters was highest within the first 2 months for both Delta (89% [95% CI, 69% to 96%]) and Omicron (73% [95% CI, 54% to 84%]) variants but waned to 49% (95% CI, 27% to 65%) for the Delta variant and 16% (95% CI, -7% to 34%) for the Omicron variant at 6 months and beyond. A third dose of BNT162b2 was associated with improved protection against the Omicron variant (87% [95% CI, 72% to 94%]) after a median (IQR) of 19 (9-32) days after dose 3. Conclusions and Relevance: These findings suggest that 2 doses of the BNT162b2 COVID-19 vaccine were associated with high levels of protection against ED and UC encounters related to the Delta and Omicron variants of SARS-CoV-2 in the first few months after vaccination. However, effectiveness waned over time, especially against Omicron. A third dose of BNT162b2 was associated with improved protection against Omicron beyond that seen initially after 2 doses, underscoring the importance of boosters for adolescents aged 12 to 17 years.
Assuntos
COVID-19 , Vacinas , Adolescente , Assistência Ambulatorial , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Casos e Controles , Criança , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , SARS-CoV-2RESUMO
BACKGROUND: Colon cancer, a potentially preventable and curable cancer, remains one of the leading causes of cancer-related death in the United States. In 2010 the researchers undertook a multifaceted initiative to reduce colon cancer mortality rates by 50% over 10 years. METHODS: A baseline literature review of preventable causes of colon cancer mortality and review of 50 deaths from colon cancer in one institution identified a set of care process improvements that could be implemented to decrease colon cancer mortality. In 2017 a second mortality review identified a second set of care process improvements that were subsequently implemented. Compliance with these processes was monitored along with age and gender-adjusted mortality rates. RESULTS: Identified care process improvements included improving the follow-up of patients with rectal bleeding and presumed iron deficiency anemia and improving the reliability of postsurgical surveillance for cancer recurrence, decreasing elapsed time from surgery to chemotherapy, increasing surgical referrals for patients with advanced colon cancer, increasing the upper age limit and overall rate of colon cancer screening, increasing vitamin D and aspirin use, and monitoring and increasing the adenoma detection rate. Compliance with these processes improved for most measures, including screening (73.7% to 79.9%), adenoma detection rates on screening colonoscopy (30% to 36% for women and 42% to 49% for men), and chemotherapy within 35 days of surgery for colon cancer (39.0% to 51.9%). Age- and gender-adjusted mortality decreased from 13.8 per 100,000 in 2009-2011 to 10.5 per 100,000 in 2016-2018. CONCLUSIONS: This quality improvement program was feasible to implement, resulted in process improvements, and decreased colon cancer mortality over seven years.
Assuntos
Adenoma , Neoplasias do Colo , Neoplasias Colorretais , Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Reprodutibilidade dos Testes , Estados UnidosRESUMO
BACKGROUND: The duration of protection against the omicron (B.1.1.529) variant for current COVID-19 vaccines is not well characterised. Vaccine-specific estimates are especially needed. We aimed to evaluate the effectiveness and durability of two and three doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine against hospital and emergency department admissions due to the delta (B.1.617.2) and omicron variants. METHODS: In this case-control study with a test-negative design, we analysed electronic health records of members of Kaiser Permanente Southern California (KPSC), a large integrated health system in California, USA, from Dec 1, 2021, to Feb 6, 2022. Vaccine effectiveness was calculated in KPSC patients aged 18 years and older admitted to hospital or an emergency department (without a subsequent hospital admission) with a diagnosis of acute respiratory infection and tested for SARS-CoV-2 via PCR. Adjusted vaccine effectiveness was estimated with odds ratios from adjusted logistic regression models. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were done for 11â123 hospital or emergency department admissions. In adjusted analyses, effectiveness of two doses of the BNT162b2 vaccine against the omicron variant was 41% (95% CI 21-55) against hospital admission and 31% (16-43) against emergency department admission at 9 months or longer after the second dose. After three doses, effectiveness of BNT162b2 against hospital admission due to the omicron variant was 85% (95% CI 80-89) at less than 3 months but fell to 55% (28-71) at 3 months or longer, although confidence intervals were wide for the latter estimate. Against emergency department admission, the effectiveness of three doses of BNT162b2 against the omicron variant was 77% (72-81) at less than 3 months but fell to 53% (36-66) at 3 months or longer. Trends in waning against SARS-CoV-2 outcomes due to the delta variant were generally similar, but with higher effectiveness estimates at each timepoint than those seen for the omicron variant. INTERPRETATION: Three doses of BNT162b2 conferred high protection against hospital and emergency department admission due to both the delta and omicron variants in the first 3 months after vaccination. However, 3 months after receipt of a third dose, waning was apparent against SARS-CoV-2 outcomes due to the omicron variant, including hospital admission. Additional doses of current, adapted, or novel COVD-19 vaccines might be needed to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by the omicron variant or future variants with similar escape potential. FUNDING: Pfizer.
Assuntos
COVID-19 , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Casos e Controles , Serviço Hospitalar de Emergência , Hospitais , Humanos , SARS-CoV-2/genética , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: High-risk medication dispenses to patients with a prior fall or hip fracture represent a potentially dangerous disease-drug interaction among older adults. The research team quantified the prevalence, identified risk factors, and generated patient and provider insights into high-risk medication dispenses in a large, community-based integrated health system using a commonly used quality measure. METHODS: This was a mixed methods study with a convergent design combining a retrospective cohort study using electronic health record (EHR) data, individual interviews of primary care physicians, and a focus group of patient advisors. RESULTS: Of 113,809 patients ≥ 65 years with a fall/fracture in 2009-2015, 35.4% had a potentially harmful medication dispensed after their fall/fracture. Most medications were prescribed by primary care providers. Older age, male gender, and race/ethnicity other than non-Hispanic White were associated with a reduced risk of high-risk medication dispenses. Patients with a pre-fall/fracture medication dispense were substantially more likely to have a post-fall/fracture medication dispense (hazard ratio [HR]â¯=â¯13.26, 95% confidence interval [CI]â¯=â¯12.91-13.61). Both patients and providers noted that providers may be unaware of patient falls due to inconsistent assessments and patient reluctance to disclose falls. Providers also noted the lack of a standard location to document falls and limited decision support alerts within the EHR. CONCLUSION: High-risk medication dispenses are common among older patients with a history of falls/fractures. Future interventions should explore improved assessment and documentation of falls, decision support, clinician training strategies, patient educational resources, building trusting patient-clinician relationships to facilitate long-term medication discontinuation among persistent medication users, and a focus on fall prevention.