Pfizer (Ireland)

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.

Respiratory infections cause substantial morbidity and mortality in older adults and other at-risk adult populations. Despite the availability of effective vaccines, adult vaccination coverage remains suboptimal. This narrative review examines strategies designed to improve vaccine uptake among non-pregnant adults aged ≥18 years and inform future adult vaccination strategies. We conducted a targeted literature search using keywords for vaccination, respiratory diseases, strategy/program/implementation, and adults in PubMed database and CDC, WHO, and ECDC websites, between 2014 and 2024. A snowball search of literature reviews and key references was also performed to identify additional relevant studies. Eligible publications focused on vaccination strategies against influenza, COVID-19, and pneumococcal disease targeting non-pregnant adults (≥18 years). We categorized the strategies by intervention type to describe their influence on vaccination campaigns and vaccine uptake/coverage. We included 45 publications, encompassing strategies focused on individual decision-making, healthcare system functions, and national policy. Educational and awareness interventions (such as healthcare worker/provider recommendations during consultation, phone calls, letters, text messages, and social media outreach) reportedly raised vaccination rates. Access-related factors, including convenient vaccination sites and free or subsidized vaccines, were reported to be important factors in improving coverage in underserved communities. Within healthcare settings, strategies such as continuous vaccine provider training and workflow/process optimization were shown to enhance vaccination delivery. At the local or national policy levels, legislation governing program targets shaped immunization efforts and facilitated collaborations and partnerships to expand campaign reach. The findings may inform policymakers and public health/immunization practitioners in designing context-specific immunization initiatives that effectively reach adult populations.

Most patients with relapsed or refractory multiple myeloma (RRMM) have previously received lenalidomide (LEN) and proteasome inhibitors (PIs). This real-world study describes treatment patterns and clinical outcomes for RRMM patients post-LEN and PI in Germany. The BasecaMMp cohort included patients with prior LEN and PI therapy within the first to third line of treatment (LOT) between May 2016 and December 2023. Patient characteristics, treatment regimens and progression-free survival (PFS), overall survival (OS) and time to next treatment (TTNT) were analyzed. Of 1834 patients included (median age: 72.5 years; 59.5% male; median of 2 prior LOTs), around 30.4% were double-refractory, and 47.7% were LEN-refractory. Index therapies (first therapies received after exposure to LEN and a PI in the first to third lines) were highly heterogeneous. Median PFS was 12.7 (95% confidence interval [CI], 12.2-13.14) months overall and 11.3 (95% CI, 10.3-12.1) months in LEN-refractory patients, while median OS was 37.1 (95% CI, 34.2-40.7) months overall and 34.3 (95% CI, 31.1-41.0) months in LEN-refractory patients. These findings highlight the lack of a clear standard of care, poor clinical outcomes, and the need for more effective therapies and treatment strategies for this population.

RSV incidence in adults is frequently underestimated due to non-specific symptomatology, limited standard-of-care testing, and lower test sensitivity compared to infants. We conducted a retrospective observational study to estimate RSV-attributable incidence of specific types of cardiorespiratory hospitalizations among adults in Germany between 2015 and 2019. Information on hospitalizations and the number of people at risk of hospitalization (denominator) was gathered from a Statutory Health Insurance database. A quasi-Poisson regression model accounting for periodic and aperiodic time trends and virus activity was fitted to estimate the RSV-attributable incidence rate (IR) of four specific cardiovascular hospitalizations (arrhythmia, ischemic heart diseases, chronic heart failure exacerbations, and cerebrovascular diseases) and four specific respiratory hospitalizations (influenza/pneumonia, bronchitis/bronchiolitis, chronic lower respiratory tract diseases, and upper respiratory tract diseases). The estimated RSV-attributable IRs of hospitalizations generally increased with age. Among estimated cardiovascular hospitalizations in adults aged ≥ 60 years, arrhythmia and ischemic heart diseases accounted for the highest incidence of RSV-attributable events, followed by chronic heart failure exacerbation, with annual IR ranges of 157-260, 133-214, and 105-169 per 100,000 person-years, respectively. The most frequent RSV-attributable respiratory hospitalizations in adults aged ≥ 60 years were estimated for chronic lower respiratory tract diseases and bronchitis/bronchiolitis, with annual IR ranges of 103-168 and 77-122 per 100,000 person-years, respectively. RSV causes a considerable burden of respiratory and cardiovascular hospitalizations in adults in Germany, similar to other respiratory viruses (e.g., influenza and SARS-CoV-2). This highlights the need to implement effective prevention strategies, especially for older adults.

In this paper, we present the development of a safe water-based synthesis of 1,2,3-triazole using cheap raw materials. Starting from glyoxal and hydrazine, a safe and efficient three-step end-to-end continuous process was developed. This protocol transforms heterogeneous batch reactions into a homogeneous streamlined continuous flow system. This advancement not only obviated the separation of hazardous intermediates, thereby mitigating potential risks, but also significantly diminished the reaction time of each step. This has ensured a rapid and stable supply of 1,2,3-triazole for downstream product development such as tazobactam. Additionally, the study delves into the insights gained from transitioning from batch reactions to continuous flow processes, highlighting the practical and safety benefits of continuous flow synthesis.

Respiratory syncytial virus (RSV) causes a substantial disease burden among infants. In older children and adults, incidence is underestimated due to nonspecific symptoms and limited standard-of-care testing. We aimed to estimate RSV-attributable hospitalizations and deaths in Spain during 2016-2019. Nationally representative hospitalization and mortality databases were obtained from the Ministry of Health and the National Statistical Office. A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends and viral activity, while allowing for potential overdispersion. In children, the RSV-attributable respiratory hospitalization incidence was highest among infants aged 0-5months (3998-5453 cases/100,000 person-years, representing 72% of all respiratory hospitalizations) and decreased with age. In 2019, estimated rates in children 0-5, 6-11, 12-23months and 6-17years were approximately 1.3, 1.4, 1.5, and 6.5 times higher than those based on standard-of-care RSV-specific codes. In adults, the RSV-attributable cardiorespiratory hospitalization rate increased with age and was highest among persons ≥ 80years (1325-1506 cases/100,000, 6.5% of all cardiorespiratory hospitalizations). In 2019, for persons aged 18-49, 50-59, 60-79, and ≥ 80years, estimated rates were approximately 8, 6, 8, and 16 times higher than those based on standard-of-care RSV-specific codes. The RSV-attributable cardiorespiratory mortality rate was highest among ≥ 80 age group (126-150 deaths/100,000, 3.5-4.1% of all cardiorespiratory deaths), when reported mortality rate ranged between 0 and 0.5/100,000. When accounting for under-ascertainment, estimated RSV-attributable hospitalizations were higher than those reported based on standard-of-care RSV-specific codes in all age groups but particularly among older children and older adults. Like other respiratory viruses, RSV contributes to both respiratory and cardiovascular complications. Efficacious RSV vaccines could have a high public health impact in these age and risk groups.

Recent studies have reported very low capacity during sterile filtration of glycoconjugate vaccines due to rapid fouling of the sterile filter. The objective of this study was to explore the potential for significantly increasing the capacity of the sterile filter through the use of an appropriate prefilter. Data were obtained using prefilters with different pore size and chemistry, with the sterile filtration performed at constant filtrate flux using 0.22 μm nominal pore size Durapore® polyvinylidene difluoride membranes. Prefiltration through 5μm pore size Durapore® or Nylon prefilters nearly eliminated the fouling of the sterile filter, leading to more than a 100-fold reduction in the rate of pressure increase for the sterile filter. This dramatic improvement in sterile filter performance was due to the removal of large components (greater than 1 μm in size) as confirmed by dynamic light scattering. These results demonstrate the potential of using large pore size prefilters to significantly enhance the performance of the sterile filtration process for the production of important glycoconjugate vaccines.