Pfizer (United States)

Several risk factors for progression to severe COVID-19have been identified, but whether multiple concomitant risk factors (risk stacking) further increase risk remains unknown. We sought to identify outpatient populations at the highest risk for severe COVID-19 using risk factor stacking. We conducted a retrospective cohort study of Veterans Affairs (VA) outpatient adults (≥ 18years) at high risk for severe COVID-19 with a positive SARS-CoV-2 test or COVID-19 diagnosis between April 1, 2022 and August 21, 2024. Severe COVID-19 was defined as COVID-19-related hospitalization or all-cause mortality within 30days. Logistic regression models were used to quantify the impact of combinations of multiple risk factors (stacked risks) on severe COVID-19. Risk factors, selected based on prevalence and CDC criteria, included age ≥ 50years, chronic lung disease, cancer, neurological conditions/cerebrovascular disease, chronic kidney disease, chronic liver disease, diabetes mellitus, heart conditions, mental health conditions, obesity, smoking, immunosuppression, hypertension, and not being up to date on COVID-19 vaccination. Among 379,144 VA outpatients with COVID-19, 1.5% (5801) had severe outcomes within 30days. Risk increased with each additional factor from two (adjusted odds ratio [aOR] 2.10, 95% confidence interval [CI] 1.37-3.23) to 14 risk factors (aOR 43.49, 95%CI 4.94-382.66) compared to one. Overall, 239 significant risk factor combinations were identified. Hypertension appeared in 196 combinations (82.0%), not up-to-date on COVID-19 vaccination in 173 combinations (72.4%), smoking in 168 combinations (70.3%), and heart conditions in 154 combinations (64.4%). The combination with the highest risk (aOR 35.25, 95%CI 16.06-77.37) included age ≥ 50years, chronic lung disease, neurological conditions/cerebrovascular disease, diabetes mellitus, heart conditions, smoking, hypertension, and not being up-to-date on COVID-19 vaccination. In this large national cohort, severe COVID-19 risk increased with the number of risk factors present. Patients with multiple overlapping risk factors who were not vaccinated were at the highest risk for severe COVID-19. As recommendations have shifted toward risk-based clinical decision-making, identifying patients with particularly high-risk combinations of conditions is increasingly important to support targeted vaccination and timely antiviral treatment.

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among older adults. Limited information is available in Israel regarding RSV outcomes, particularly compared to influenza, to guide strategies for RSV vaccination. This study aimed to characterize RSV infection and predictors of clinical outcomes among hospitalized adults aged ≥ 60years in Israel between 2016 and 2023, and to compare disease severity and outcomes with those of seasonal influenza hospitalizations. A retrospective analysis was conducted of hospitalized adults aged ≥ 60years with positive RSV or influenza confirmed via standard-of-care RT-PCR between 2016 and 2023. The primary outcome was a composite of intensive care unit (ICU) admission, mechanical ventilation, vasopressor support, or 30-day mortality. Cardiovascular complications were recorded. An inverse probability treatment weighting (IPTW) was used to adjust for potential confounding. Weighted and unweighted relative risks (RRs) were estimated to compare clinical outcomes between RSV and influenza. Overall, 817 RSV-positive and 2113 influenza-positive patients were included. Among patients with RSV, 30-day and 90-day mortality rates were 11.9% and 18.8% respectively; ICU admission was required for 10.6%, mechanical ventilation for 6.4%, and vasopressor support for 6.5%. Tachyarrhythmia was documented in 17.7% and ischemia in 9.9%. Predictors of the composite primary outcome included chronic pulmonary disease, lower respiratory tract infection, hypothermia, elevated pulse, lower blood pressure and increased creatinine. In IPTW-adjusted analyses, RSV infection had a trend for increased risk for the composite primary outcome (RR 1.03, 95% confidence interval [CI] 1.00, 1.06) and 90-day mortality (RR 1.02, 95%CI 0.99, 1.05) compared with influenza. Among hospitalized older adults, RSV infection carries considerable morbidity and mortality and may have a higher risk for poor clinical outcomes compared with influenza. These findings support the prioritization of RSV vaccination programs among older adults.

With the rising prevalence of aging worldwide, there is a necessity for reliable and frequent assessments of older individuals' health status to manage and potentially prevent age-related complications. Digital health technologies (DHTs), such as wearable devices, provide an opportunity to gather objective, continuous, and unobtrusive measurements, enabling effective health management in everyday life. We aimed to evaluate the relationship between digital endpoints and frailty, nutritional status, and patient-reported outcomes (PROs) in older individuals, as well as quantified their compliance and comfort with DHTs. In two cross-sectional studies, namely the Geriatric Anorexia Studies 1 and 2, including three in-clinic visits and 2-3 weeks of at-home monitoring, 94 participants (mean age 72.98 years, SD 6.28 years) were stratified based on their frailty status (n=39, 41%, nonfrail; n=45, 48%, prefrail; and n=10, 11%, frail) and nutritional status (n=70, 74%, with normal nutrition and n=24, 26%, at risk for malnutrition), as assessed in a clinical setting using the Fried Frailty Score and the Simplified Nutritional Appetite Questionnaire, respectively. We remotely monitored older adults using different DHTs. At home, participants were monitored with a wrist accelerometer for physical activity, continuous glucose monitoring (CGM) for glucose concentration, a digital body scale for weight and body composition, and a digital nutritional scale for meal tracking. Compliance with devices was assessed via wear time and correct at-home usage, while comfort was evaluated using questionnaires. The association between digital endpoints and frailty/nutritional status was investigated via linear regression, followed by ANOVA, and the relationship between digital endpoints collected at home and PROs was evaluated via Spearman's ρ. Weight and body composition were also assessed during in-clinic visits with a research-grade scale, used to validate the at-home digital body scale measurements, via the intraclass correlation coefficient, Pearson's R, and Bland-Altman plots with mean bias. Physical activity digital endpoints collected at home were significantly different across frailty and nutritional groups and significantly correlated with self-reported appetite, fatigue, and physical function (eg, for mean daily activity in the maximum 60 minutes of activity, ρ=0.28, -0.23, and 0.47, respectively). More than 80% of participants reported that all devices were mostly to very acceptable to wear/use: 95% (88/93) for the body scale, 86% (43/50) for CGM, 80% (40/50) for the nutrition scale, and 91% (84/93) for the wrist accelerometer. Compliance ranged from 60% of monitoring days for the digital nutrition scale to 90% for the wrist accelerometer. Physical activity digital endpoints show clear prognostic significance for frailty and malnutrition in older individuals and reflect self-reported measures. DHTs can be reliably deployed at home for older individuals to measure their physical activity, weight and body composition, glucose concentration, and meal intakes, thus enabling patient-centric, data-centric clinical trials. ClinicalTrials.gov NCT04858932; https://clinicaltrials.gov/study/NCT04858932; ClinicalTrials.gov NCT05211973; https://clinicaltrials.gov/study/NCT05211973.

For patients with advanced breast cancer (ABC), standard-of-care (SOC) treatment in first line (1L) with CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) is well established. However, data on treatment patterns in second line (2L), where the treatment landscape is evolving, are lacking. This large real-world study investigated treatment sequencing from 1L to 2L in patients with HR+/HER2- ABC in the post-CDK4/6i era. Data leveraged the Adelphi ABC Disease Specific Programme (DSP)™, a cross-sectional survey conducted in Europe and the United States between July 2022 and March 2023. Physicians provided data for consecutively consulting patients, including current and historic clinical status, treatment sequencing and biomarker testing history. All analyses were descriptive. Data for 767 patients with HR+/HER2- ABC receiving 2L treatment at data collection were analyzed. In 2L, 31.6% received chemotherapy-based regimens, 17.7% received ET monotherapy, 21.5% received CDK4/6i+ET, and 26.3% received a targeted therapy (mTOR/PARP/PI3K inhibitors). Of those receiving 2L, 58% previously received a CDK4/6i regimen in 1L, in line with treatment guidance, while 21% received chemotherapy. Use of targeted therapies in 2L was driven by biomarker testing. Country/region-specific variation in biomarker testing and treatments were likely due to differences in local guidance and practice. This study provides insights into treatment sequencing in patients with HR+/HER2- ABC who progress to 2L in the post-CDK4/6i era. For patients without targetable mutations, there is no clear SOC at 2L and treatment options are limited. New treatments may further shape this developing landscape.

To evaluate diabetic ketoacidosis (DKA) risk among new users of ertugliflozin versus sulfonylureas (SU) or thiazolidinediones (TZD) and incretin-based drugs in patients with type 2 diabetes. We used Medicare and Medicaid fee-for-service adjudicated claims within the Innovation in Medical Evidence and Development Surveillance network to identify three new-user cohorts: (1) ertugliflozin; (2) SU/TZD; and (3) incretin-based drugs. The outcome was a principal hospital discharge diagnosis for DKA. Adjusted hazard ratios (HRs) were estimated after 1:1 propensity score (PS) matching, separately for ertugliflozin vs. SU/TZD and vs. incretin-based drugs. Subgroup analyses were performed based on baseline insulin use. After PS matching, baseline characteristics were similarly distributed in each cohort. For ertugliflozin (n = 42,907) vs. SU/TZD (n = 42,907), the incidence rates of DKA per 1000 person-years (PY) were 2.95 and 1.49, respectively. For ertugliflozin (n = 42,247) vs. incretin-based drugs (n = 42,247), the incidence rates of DKA per 1000 PY were 2.76 and 1.06, respectively. For ertugliflozin vs. SU/TZD, the HR [95% confidence interval (CI)] was 1.88 [1.17-3.02]; in non-insulin users, 2.34 [1.27-4.31]; and in insulin users, 1.17 [0.54-2.52]. For ertugliflozin vs. incretin-based drugs, the HR [95% CI] was 2.40 [1.40-4.11]; in non-insulin users, 2.84 [1.42-5.66]; and in insulin users, 1.87 [0.79-4.46]. Ertugliflozin was associated with a higher risk of DKA relative to comparators. HRs were higher among new users with no-concomitant insulin use than those with concomitant insulin use. Results were consistent with prior SGLT2i data and highlighted the importance of caution by both patients and physicians.

The "100 Days Mission" aims to compress the timeline for delivering safe and effective vaccines in response to future pandemics. Here, we present insights from Pfizer leaders involved in the COVID-19 vaccine effort on key enablers for rapid large-scale manufacture of pandemic vaccines to achieve this ambitious goal. For pharmaceutical companies, these enablers include robust governance models, secure supply chains, innovative production strategies, and maintained "warm" manufacturing capacity. Additionally, we examine the crucial role of government support through regulatory harmonization, enhanced global surveillance, and improved logistics. By addressing these critical factors, the global community can better prepare for rapid vaccine manufacturing in response to future pandemic threats.

Abstract A novel 3D-printed platform for photochemical reaction miniaturization has been designed, created, and characterized to expedite photoredox reaction optimization. The system offers two configurations, supporting throughput of 16 or 96 parallel experiments. This approach provides a cost-effective and sustainable strategy to access large datasets with minimal economic burden, allowing its implementation in virtually all research groups interested in photochemistry. Initial characterization data for both configurations and blueprints of the 3D-printed device are provided to ensure rapid and straightforward implementation.

Advances in prostate cancer (PC) therapy have improved survival and expanded systemic treatment options. To support treatment decision-making, it is important to understand tradeoffs patients are willing to make between survival and other factors such as side effects. This targeted literature review evaluated the results of discrete-choice experiment (DCE) studies assessing patients' and healthcare professionals' (HCPs') preferences for systemic therapies for PC. PubMed was searched for PC DCE studies evaluating patient or HCP preferences for systemic treatment published through April 2025. Attribute importance rankings were summarized descriptively and stratified by respondent type and by PC stage corresponding to the treatments assessed. Studies primarily assessing preferences for androgen deprivation therapy, which is used in patients with biochemically recurrent non-metastatic castration-sensitive PC, were categorized as "earlier stage"; those assessing systemic combination therapies for metastatic or castration-resistant PC were categorized as "late stage." Seventeen eligible studies were included (late-stage PC treatments, n = 10 patient studies and n = 3 HCP studies; earlier-stage PC treatments, n = 4 patient studies, with one reporting an HCP subgroup). Overall, patients and HCPs showed the strongest preferences for attributes related to efficacy outcomes (e.g.,extending overall survival, clinical progression). Preferences for avoidance of long-term safety attributes, such cardiovascular side effects, were generally ranked higher in late-stage studies than in earlier-stage studies. Meanwhile, avoidance of short-term tolerability attributes, such as injection-site reaction and sexual function, were prioritized and measured only in earlier-stage studies. Preferences differed between respondent types for late-stage treatments, with HCPs placing greater importance on tolerability attributes (fatigue, central nervous system side effects) and patients prioritizing safety (avoiding falls, cardiovascular side effects). Despite differences in safety and tolerability attribute rankings among respondents across earlier-stage and late-stage PC treatments, efficacy outcomes were most important to patients and HCPs.