Evaluation of MMV Pandemic Response Box compounds to identify potent compounds against clinically relevant bacterial and fungal clinical isolates in vitro.

Background: Multidrug resistant bacterial and fungal pathogens are resistant to a number of significant front-line drugs, hence, identification of new inhibitory agents to combat them is crucial. In this study, we aim to evaluate the activity of Pandemic Box compounds from Malaria Medicines Venture (MMV) against A. baumannii and P. aeruginosa bacterial, C. auris, C. albicans and A. niger fungal clinical isolates. Methods: Isolates were initially screened with 201 antibacterial and 46 antifungal compounds (10 µM) using a microbroth dilution in triplicates to determine MIC. A persister assay was performed for bacterial pathogens. Results: Out of 201 antibacterial compounds, twenty-nine and seven compounds inhibited the growth of A. baumannii and P. aeruginosa at 10 µM, respectively. MMV1580854, MMV1579788, eravacycline and epetraborole inhibited both the bacterial test isolates. In a persister assay, MMV1634390 showed complete bactericidal effect against A. baumannii. With antifungal activity compounds, C. auris responded to15 compounds, Six compounds inhibited C. albicans and one was effective against A. niger at 10 µM. The ratio of Minimum Fungicidal Concentration (MFC): Minimum Inhibitory Concentration (MIC) of MMV1782110 was 2 against C. auris. Eberconazole, amorolfine and luliconazole are fungicidal targeting C. albicans at a MFC: MIC ratio of 2. Conclusion: Five compounds from MMV Pandemic Box were found to be inhibiting colistin and ceftazidime resistant A. baumannii clinical isolate, also against colistin and ß-lactam resistant P. aeruginosa clinical isolate. MMV1634390 showed complete bactericidal effect against A. baumannii in a persister assay. MMV1782110, Eberconazole, amorolfine and luliconazole exhibited potent anti-fungal activity. Further investigations are warranted to identify the targets and mechanism.

Validity of the Health Personality Assessment among rectal cancer survivors in Serbia.

Understanding health personality traits in rectal cancer survivors could help to optimize recovery and coping mechanisms. The objective of this study was to evaluate psychometric properties of the Health Personality Assessment in Serbian language among rectal cancer survivors. A cross-sectional study was carried out from June to December 2022. The study sample consisted of 76 people who underwent the open lower anterior resection for rectal carcinoma at the Clinic for Digestive Surgery and the Clinic for Emergency Surgery, University of Clinical Center of Serbia (Belgrade, Serbia) and whose ileostomy was closed. Study participants were interviewed over the telephone using the Serbian version of the HPA which was translated according to the internationally accepted methodology for translation and adaptation of questionnaires. The confirmatory factor analysis suggested that the fit indices for 5-factor structure of the HPA were acceptable-to-good: Goodness of fit index = 0.939; Tucker Lewis fit index = 0.989; Comparative fit index = 0.992; Root Mean Square Error of Approximation = 0.019. Cronbach's alpha coefficients for Health Neuroticism, Health Extraversion and Health Agreeableness were>0.7 and for Health Openness and Health Conscientiousness were >0.4. Predictive validity testing suggested that not having complications with the ileostomy and a longer time since ileostomy closure were associated with stronger Health Agreeableness. Also, a longer time since ileostomy closure was associated with stronger Health Conscientiousness. The Serbian version of the HPA showed good construct validity and acceptable internal consistency. This is an important tool in further research of personality and health outcomes among rectal cancer survivors.

Cross-sectional and longitudinal associations between late-life depressive symptoms and cognitive deficits: 20-year follow-up of the Kuakini Honolulu-Asia aging study.

OBJECTIVE: To examine depressed affect, somatic complaints, and positive affect as longitudinal predictors of fluid, crystallized and global cognitive performance in the Kuakini Honolulu-Asia Aging Study (HAAS), a large prospective cohort study of Japanese-American men. METHODS: We assessed 3,088 dementia-free Kuakini-HAAS participants aged 71-93 (77.1 ± 4.2) years at baseline (1991-1993). Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression (CES-D) Scale. Baseline CES-D depression subscales (depressed and positive affects; somatic complaints) were computed. The Cognitive Abilities Screening Instrument (CASI) measured cognitive performance on a 100-point scale; fluid and crystallized cognitive abilities were derived from CASI factor analysis. Cognition was also evaluated at 4 follow-up examinations over a 20-year period. Multiple regression assessed baseline CES-D subscales as predictors of cognitive change. The baseline covariates analyzed were CASI, age, education, prevalent stroke, APOE ε4 presence, and the longevity-associated FOXO3 genotype. RESULTS: Cross-sectionally, baseline CES-D subscales were related to cognitive measures; e.g., higher depressed affect was associated with lower crystallized ability (ß = -0.058, p ≤ 0.01), and somatic complaints were linked to poorer fluid ability (ß = -0.045, p ≤ 0.05) and to worse global cognitive function as measured by total CASI score (ß = -0.038, p ≤ 0.05). However, depression subscales did not significantly or consistently predict fluid ability, crystallized ability, or global cognitive performance over time. CONCLUSION: Psychological and physical well-being were associated with contemporaneous but not subsequent cognitive functioning. Assessment of depressive symptoms may identify individuals who are likely to benefit from interventions to improve mood and somatic health and thereby maintain or enhance cognition.

Surveillance of global, travel-related illness using a novel app: a multivariable, cross-sectional study.

INTRODUCTION: Current traveller health surveillance is 'top-down'. Mobile-based surveillance could capture infection symptoms in real time. We aimed to evaluate the spectrum of illness in travellers using a mobile app-based system. METHODS: This study (ClinicalTrials.gov NCT04672577) used an application called Infection Tracking in Travellers (ITIT) that records travel-related illness symptoms with associated geolocation and weather data. The free ITIT app is available in 14 languages. Participants were recruited globally from April 2022 to July 2023. Participants >18 years of age travelled internationally and provided electronic consent. Incentives included the provision of travel health information imported from the WHO website. Symptoms were recorded with daily pop-up questionnaires and symptom severity was assessed using a Likert scale. Two post-travel questionnaires were administered. Logistic mixed models examined factors relating to symptom presence, and a random forest model examined symptom impact. RESULTS: 609 participants were recruited until July 2023. Participants had an average age of 37 years (18-79), and an average travel duration of 26 days (2-281). Most participants were travelling for leisure/tourism (401; 66%), followed by 'visiting friends and relatives' (99; 16%) and business travel (80; 13%). All continents were visited by at least one traveller. Of 470 registered trips, symptoms were reported on 163 trips (35%). Gastrointestinal symptoms were reported on 87 trips (19%) and respiratory symptoms on 81 trips (17%). The most important factors in predicting the presence of symptoms were duration of travel, travelling in winter and high humidity. Diarrhoea, headache and nausea were symptoms with most impact on daily activities. Post-travel questionnaires showed that 12% of surveyed participants experienced symptoms with several episodes of self-treatment. Two diagnoses were recorded: Lyme disease and amoebic dysentery. CONCLUSION: The digital tool ITIT successfully captures the spectrum of travel-related illness. This detailed epidemiology is crucial for outbreak detection and for the formulation of travel medicine guidelines. TRIAL REGISTRATION NUMBER: NCT04672577.

Evaluating Lab-Based Eligibility Criteria by Race/Ethnicity in Clinical Trials of Diffuse Large B-Cell Lymphoma.

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy (IC) would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 lab-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Utilizing data from the prospectively enrolled Lymphoma Epidemiology Outcomes (LEO) Cohort study, with demographics broadly similar to the U.S. patients diagnosed with lymphoma, we evaluated the impact of laboratory eligibility criteria from recent first-line DLBCL trials across various racial and ethnic backgrounds. There were significant differences in the baseline lab values by race/ethnicity with Black/African American (AA) patients having the lowest mean hemoglobin and highest creatinine clearance. Based on recent clinical trial eligibility criteria, AA and Hispanic patients had higher rates of lab-based ineligibility compared to Non-Hispanic Whites. The largest gap in the clinical outcomes between eligible (ref) and non-eligible patients was noted within AA patients with an overall survival hazard ratio based on POLARIX clinical trial criteria of 4.09, 95% CI: 1.83-9.14. A thoughtful approach to the utility of each criterion and cut offs for eligibility needs to be evaluated in the context of its differential impact across various racial/ethnic groups.

Recent Advancements towards Sustainability in Rotomoulding.

Rotational moulding is a unique low-shear process used to manufacture hollow parts. The process is an excellent process method for batch processing, minimal waste and stress-free parts. However, the process has drawbacks such as long cycle times, gas dependency and a limited palette of materials relative to other process methods. This review aimed to shed light on the current state-of-the-art research contributing towards sustainability in rotational moulding. The scope of this review broadly assessed all areas of the process such as material development, process adaptations and development, modelling, simulation and contributions towards applications carving a more sustainable society. The PRISMA literature review method was adopted, finding that the majority of publications focus on material development, specifically on the use of waste, fillers, fibres and composites as a way to improve sustainability. Significant focus on biocomposites and natural fibres highlighted the strong research interest, while recyclate studies appeared to be less explored to date. Other research paths are process modification, modelling and simulation, motivated to increase energy efficiency, reduction in scrap and attempts to reduce cycle time with models. An emerging research interest in rotational moulding is the contribution towards the hydrogen economy, particularly type IV hydrogen vessels.

Rational design of a bacterial import system for new-to-nature molecules.

Integration of novel compounds into biological processes holds significant potential for modifying or expanding existing cellular functions. However, the cellular uptake of these compounds is often hindered by selectively permeable membranes. We present a novel bacterial transport system that has been rationally designed to address this challenge. Our approach utilizes a highly promiscuous sulfonate membrane transporter, which allows the passage of cargo molecules attached as amides to a sulfobutanoate transport vector molecule into the cytoplasm of the cell. These cargoes can then be unloaded from the sulfobutanoyl amides using an engineered variant of the enzyme γ-glutamyl transferase, which hydrolyzes the amide bond and releases the cargo molecule within the cell. Here, we provide evidence for the broad substrate specificity of both components of the system by evaluating a panel of structurally diverse sulfobutanoyl amides. Furthermore, we successfully implement the synthetic uptake system in vivo and showcase its functionality by importing an impermeant non-canonical amino acid.

Brentuximab Vedotin Plus Ibrutinib in Relapsed and Refractory Hodgkin Lymphoma.

INTRODUCTION: Brentuximab vedotin (BV) is an antibody-drug conjugate that delivers monomethyl auristatin E (MMAE) to CD30+ cells and is safe and effective in relapsed/refractory (r/r) Hodgkin lymphoma (HL). Although most patients respond to BV, only a minority will obtain a complete response (CR), and almost all patients eventually progress. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor highly active in multiple subtypes of non-Hodgkin lymphoma; limited data exist regarding its use in HL. It irreversibly inhibits interleukin-2-inducible kinase (ITK) with Th1 based immune responses. As we previously observed preclinical synergy between ibrutinib and BV, we hypothesized ibrutinib may enhance the antitumor activity of BV in HL. We designed and conducted a phase II trial of ibrutinib plus BV in patients with R/R HL, and herein report the final primary analysis of safety and efficacy. METHODS: This was a multicenter phase II trial with a lead-in cohort in patients with r/r HL. Eligibility criteria included age ≥ 15 years with r/r HL after at least one prior line of therapy. Treatment consisted of 1.8 mg/kg BV intravenously every 3 weeks and ibrutinib 560 mg PO daily (420 mg PO daily in the lead-in cohort). Prior BV was allowed if patients were not refractory. The primary endpoint was the CR rate according to Lugano 2014. Secondary endpoints included toxicities, overall response rate (ORR), and duration of response (DOR). RESULTS: The 39 patients were enrolled onto the study, of which 67% were male; the median age was 33 (range: 17-71). 38% had extranodal disease at baseline, 51% had advanced stage disease, 51% were refractory to the prior therapy, and 21% had prior BV. Of 36 patients who were evaluable for response, the CR rate was 33% and ORR 64%; median DOR was 25.5 months. Thirteen patients proceeded to autologous transplant and 3 patients proceeded to allogeneic transplant for consolidation after response. The most common adverse events were nausea (67%), peripheral neuropathy (62%), diarrhea (59%), fatigue (46%), thrombocytopenia (46%), headache (41%), rash (41%), elevated ALT (38%), anemia (36%), vomiting (36%), abdominal pain (33%), fever (33%), and hypertension (33%). Six patients experienced unacceptable toxicity, defined as Gr 3/4 non-hematologic toxicity or non-resolving Gr 3/4 hematologic toxicity including one patient who died of multiorgan failure from suspected COVID-19 infection during cycle 1. DISCUSSION: The combination of BV and ibrutinib was active in r/r HL; however, given significant toxicity, it cannot be recommended for future development.

Randomized Bendamustine-Rituximab(R) + Bortezomib Induction and R + Lenalidomide Maintenance for Mantle Cell Lymphoma.

While initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine-rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance following induction is often utilized. Thus, the open-label, randomized phase II ECOG-ACRIN Cancer Research Group E1411 trial was designed to test two questions: 1) Does addition of bortezomib to BR induction (BVR) and/or 2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012-2016, 373 previously untreated patients, 87% ≥ 60 years old, were enrolled in this trial. At a median follow up of 7.5 years, there is no difference in the median PFS of BR compared to BVR (5.5 yrs vs. 6.4 yrs, HR 0.90, 90% CI 0.70, 1.16). There were no unexpected additional toxicities with BVR treatment compared to BR, with no impact on total dose/duration of treatment received. Independent of the induction treatment, addition of lenalidomide to rituximab did not significantly improve PFS, with median PFS in R vs LR (5.9 yrs vs 7.2 yrs, HR 0.84 90% CI 0.62, 1.15). The majority of patients completed the planned 24 cycles of LR at the scheduled dose. In summary, adding bortezomib to BR induction does not prolong PFS in treatment-naïve MCL, and LR maintenance was not associated with longer PFS compared with rituximab alone following BR. Nonetheless, the > 5 year median PFS outcomes in this prospective cooperative group trial indicate the efficacy of BR followed by rituximab maintenance as highly effective initial therapy for older MCL patients. (NCT01415752).

"It gave me a sense of achievement and a sense of purpose"-a qualitative study of patient experiences of a virtually supervised exercise program for adults with advanced cancer and cachexia.

People with advanced cancer and cachexia experience significant body weight loss, adversely impacting physical function and quality of life (QOL). Effective, evidence-based treatments for cancer cachexia are lacking, leaving patients with unmet needs. Exercise holds promise to improve patient QOL. However, information on patients' experiences of exercise, including their ability to cope with structured exercise, is limited. PURPOSE: To explore patient experiences completing a structured, supervised exercise program for people with cachexia due to advanced cancer. METHODS: Semi-structured interviews were conducted with participants enrolled in a phase II feasibility, randomized controlled trial to explore their experiences of an 8-week virtually supervised exercise program delivered via videoconference technology. Interviews were analysed using reflexive thematic analysis. RESULTS: Seventeen participants completed interviews (female n = 9, 53%). Main interview themes included the following: (1) Deciding to exercise involves balancing concerns and expectations, (2) the exercise program is a positive experience, and (3) moving forward after the exercise program. While some participants initially held doubts about their physical capabilities and exercise safety, most wanted to exercise to enhance their wellbeing. Participants described the exercise program as a positive experience, offering diverse benefits. Some would have preferred in-person exercise, but all agreed the virtual format increased convenience. Participants emphasized the need to recommend the program to others in similar circumstances. They underscored the necessity and desire for ongoing support to sustain their new exercise habits. CONCLUSION: Based on patient experiences, virtually supervised exercise programming appears to be feasible and meaningful to people with advanced cancer and cachexia.

Safety and Toxicity Profiles of CAR T Cell Therapy in Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The application of CD19-directed chimeric antigen receptor T (CAR T) cell therapy has improved outcomes for thousands of patients with non-Hodgkin B cell lymphoma (NHL). The toxicities associated with various CAR T cell products, however, can be severe and difficult to anticipate. METHODS: In this systematic review and meta-analysis, we set out to determine whether there are measurable differences in common toxicities, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), cytopenias, and infections, between CAR T products that are commercially available for the treatment of NHL. RESULTS: After a stringent study selection process, we used a cohort of 1364 patients enrolled in 15 prospective clinical trials investigating the use of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). We found that the rates of CRS and ICANS were significantly higher with axi-cel as compared to both liso-cel and tisa-cel. Conversely, we demonstrated that rates of all-grade and severe neutropenia were significantly greater with liso-cel. Febrile neutropenia and all-grade infection rates did not differ significantly between products though rates of severe infection were increased with axi-cel. CONCLUSIONS: Overall, this study serves as the first to delineate toxicity profiles associated with various available CAR T products. By better understanding associated toxicities, it may become possible to tailor therapies towards individual patients and anticipate the development of toxicities at earlier stages.

Healthy aging among centenarians and near-centenarians: Findings from the Georgia Centenarian Study.

The Georgia Centenarian Study is one of the earliest comprehensive studies on centenarians. Based on the Georgia model of adaptation, the primary purpose of this study was to assess the health and well-being of our oldest population, with a focus on several primary adaptation areas: genetics and family longevity, environmental support, individual characteristics, cognitive and behavioral skills, health behaviors, and physical and mental health, including overall life satisfaction. The results of the three Georgia Centenarian sub-studies indicate that genetic and environmental variables play an important role in determining different levels of healthy aging, but they also highlight relevant mediating and moderating effects in a network of interrelating adaptation components.

Development of Highly Potent and Selective Covalent FGFR4 Inhibitors Based on SNAr Electrophiles.

Fibroblast growth factor receptor 4 (FGFR4) is thought to be a driver in several cancer types, most notably in hepatocellular carcinoma. One way to achieve high potency and isoform selectivity for FGFR4 is covalently targeting a rare cysteine (C552) in the hinge region of its kinase domain that is not present in other FGFR family members (FGFR1-3). Typically, this cysteine is addressed via classical acrylamide electrophiles. We demonstrate that noncanonical covalent "warheads" based on nucleophilic aromatic substitution (SNAr) chemistry can be employed in a rational manner to generate highly potent and (isoform-)selective FGFR4 inhibitors with a low intrinsic reactivity. Key compounds showed low to subnanomolar potency, efficient covalent inactivation kinetics, and excellent selectivity against the other FGFRs, the kinases with an equivalent cysteine, and a representative subset of the kinome. Moreover, these compounds achieved nanomolar potencies in cellular assays and demonstrated good microsomal stability, highlighting the potential of SNAr-based approaches in covalent inhibitor design.

Defining primary refractory large B-cell lymphoma.

ABSTRACT: Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort. Patients with newly diagnosed LBCL were enrolled in the Molecular Epidemiological Resource cohort (MER; N = 949) or the Lymphoma Epidemiology of Outcomes cohort (LEO; N = 2755) from September 2002 to May 2021. Primary refractory LBCL was defined as no response (stable disease [SD]) or progressive disease (PD) during, or by the end of, frontline (1L) IC (primary PD; PPD); partial response at end of treatment (EOT PR); or relapse within 3 to 12 months after achieving CR at EOT to 1L IC (early relapse). In the MER cohort, patients with PPD had inferior overall survival (OS; 2-year OS rate: 15% MER, 31% LEO) when compared with other subgroups considered in defining primary refractory disease, EOT PR (2-year OS rate: 38% MER, 50% LEO) and early relapse (2-year OS rate: 44% MER, 58% LEO). Among patients receiving 1L IC with curative intent, we identified that patients with PPD are the key subgroup with poor outcomes. We propose a definition of primary refractory LBCL as SD or PD during, or by the end of, 1L treatment.

Tackling Challenges in Assessing the Economic Value of Tumor-Agnostic Therapies: A Cost-Effectiveness Analysis of Pembrolizumab as a Case Study.

OBJECTIVES: Assessing the value of tumor-agnostic drugs (TAD) is challenging given the potential variability in treatment effects, trials with small sample sizes, different standards of care (SoC), and lack of comparative data from single-arm basket trials. Our study developed and applied novel methods to assess the value of pembrolizumab compared with SoC to inform coverage decisions. METHODS: We developed a partitioned survival model to evaluate the cost-utility of pembrolizumab for previously treated patients with 8 advanced or metastatic microsatellite instability-high or mismatch repair-deficient cancers from a US commercial payer perspective. Efficacy of pembrolizumab was based on data from trials directly or with adjustment using Bayesian hierarchical models. Eight chemotherapy-based external control arms were constructed from the TriNetX electronic health record databases. Tumor-specific health-state utility values were applied. All costs were adjusted to 2022 US dollars. RESULTS: At a lifetime horizon, pembrolizumab was associated with increased effectiveness compared with chemotherapies in colorectal (quality-adjusted life years [QALYs]: +0.64, life years [LYs]: +0.64), endometrial (QALYs: +3.79, LYs: +5.47), and small intestine cancers (QALYs: +1.73, LYs: +2.48), but not for patients with metastatic gastric, cholangiocarcinoma, pancreatic, ovarian, and brain cancers. Incremental cost-effectiveness ratios varied substantially across tumor types. Pembrolizumab was found to be cost-effective in treating colorectal and endometrial cancers (incremental cost-effectiveness ratios: $121 967 and $139 257, respectively), and not cost-effective for other assessed cancers at a $150 000 willingness-to-pay/QALY threshold, compared with SoC chemotherapies. CONCLUSIONS: The cost-effectiveness of TADs can vary by cancers. Using analytic tools such as external controls and Bayesian hierarchical models can tackle several challenges in assessing the value of TADs and uncertainties from basket trials.

Modelling the Public Health Burden of Herpes Zoster and the Impact of Adjuvanted Recombinant Zoster Vaccine in Five Selected Countries in Southeast Asia.

INTRODUCTION: Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50 years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. METHODS: For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. RESULTS: Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. CONCLUSIONS: This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article.

The mediating effect of eHealth literacy on the relationship between health personality and quality of life in community-dwelling older adults.

AIMS: To explore the relationship between health personality and quality of life among community-dwelling older adults and to examine the mediating effect of eHealth literacy on this relationship. METHODS: A total of 413 community-dwelling older adults from central China were recruited from September 2022 to January 2023. A cross-sectional investigation was conducted using the Chinese versions of the Health Personality Assessment (HPA), eHealth Literacy Scale (eHEALS), and 12-item Short Form Health Survey (SF-12). Correlations between the three variables were examined by Pearson analysis, and mediation analysis was conducted to explore the direct, indirect, and total effects of the health personality on quality of life vis-à-vis eHealth literacy. RESULTS: Health personality factors (including health neuroticism, health openness, and health conscientiousness), eHealth literacy, and quality of life are significantly correlated (P<0.05); eHealth literacy can play a significant mediating role in the relationship between health neuroticism (ß= -0.256, 95 %CI: [-0.405, -0.119]), health openness (ß = 0.488, 95 % CI: [0.343,0.652]), health conscientiousness (ß= 0.489, 95 % CI: [0.354, 0.634]) and quality of life. CONCLUSION: This study revealed that the effect of health personality factors (including health neuroticism, health openness, and health conscientiousness) on quality of life in older adults was mediated through eHealth literacy. IMPACT: Individual personality is essential to understanding eHealth literacy and quality of life among community-dwelling older adults. It may be helpful to identify the health personality traits of older adults first, then implement targeted interventions accordingly to enhance eHealth literacy and ultimately improve quality of life.

Trend of measles-rubella vaccination coverage and impact on measles epidemiology in the Savannah Region, Ghana; 2018-2022: A secondary data analysis.

INTRODUCTION: Ghana witnessed an outbreak of measles in 2022 following the COVID-19 pandemic, and Savannah Region was among the regions severely impacted. The objective of this study was to conduct trend analysis of measles case incidence and measles-rubella (MR) vaccination coverage in the Savannah Region to identify gaps and propose remedial actions to mitigate future outbreaks of vaccine preventable diseases (VPDs). METHODS: Analysis of measles surveillance and measles-rubella vaccination data for 2018-2022 was conducted to assess relationship between immunization coverage and measles case incidence. Data were extracted from the District Health Information Management System (DHIMS) platform and loaded into Microsoft Excel 16.0 spreadsheet for analysis. Coverages for first (MR1) and second (MR2) doses of measles-rubella vaccination, dropout rates, and measles incidence (per 100,000) were calculated. RESULTS: The coverage trend for both vaccine doses followed similar trajectories, increasing from 2018 to a peak in 2019, and declining sequentially thereafter to the lowest (for the study period) in 2022. Generally, MR1/MR2 dropout rate was high across all districts during the entire study period. The regional incidence of confirmed measles rose sharply from less than 1/1,000,000 in 2018-2021 to 94 in 2022. Wide variations in vaccination coverage and dropout rates were observed among the districts. There was moderate to fairly strong negative correlation between MR vaccination coverage and measles case incidence. CONCLUSIONS: The MR vaccination coverage in the Savannah Region declined probably due to pre-existing weaknesses in the immunization programme accentuated by impact of the COVID-19 pandemic. The lowered population immunity likely contributed to occurrence of the measles outbreak in 2022. Pragmatic actions are needed to catch-up on missed children, restore coverage to pre-pandemic levels, and strengthen the immunization programme as part of global efforts towards achieving the Immunization Agenda 2030 (IA2030) trajectory.