This study evaluated the effectiveness of a brief, Theory of Planned Behavior-based educational program on weight management and related health outcomes among university employees. In this quasi-experimental study conducted at two major universities in Erbil, Iraq, 200 employees with a body mass index (BMI) ≥ 25 kg/m² self-selected into an intervention (n = 100) or control (n = 100) group. The intervention consisted of five individual 35-40-minute sessions delivered over 12 weeks and covered obesity awareness, culturally adapted nutrition education, physical activity, and behavior-change strategies. The control group received only standard written materials. Primary outcomes were changes in body weight, BMI, and waist circumference. Secondary outcomes included lipid profile, fasting glucose, quality of life (Impact of Weight on Quality of Life-Lite [IWQOL-Lite]), dietary quality, and physical activity. All assessments were performed at baseline and 12 weeks. The intervention was associated with a mean weight loss of 7.46 kg (95% CI 6.44-8.48) compared with a gain of 0.58 kg in the control group (adjusted difference - 8.04 kg; p < 0.001; Cohen's d = 2.40). 79% of intervention participants lost ≥ 5% of their initial body weight (versus 0% in controls), and 41% lost ≥ 10%. Significant improvements were also observed in BMI, waist circumference, lipid profile, quality of life, and dietary quality (all p < 0.001; d > 1.8). Mediation analysis indicated that improvement in dietary quality accounted for 82% of the observed association between group assignment and change in BMI. A brief, low-cost, culturally adapted educational intervention delivered in the workplace was associated with exceptionally large weight loss, cardiometabolic benefits, and psychosocial gains, with perfect retention. These findings suggest that this model may offer a promising approach for obesity management in Middle Eastern settings. However, confirmation in randomized controlled trials with longer follow-up is required before firm conclusions regarding scalability and effectiveness can be drawn. The study was not prospectively registered in a clinical trial registry because it employed a quasi-experimental design with participant self-selection rather than random allocation. However, the full study protocol including all primary and secondary outcomes, eligibility criteria, intervention details, and the statistical analysis plan was finalized, approved by the Hawler Medical University Ethics Committee (reference HMU-REC-2024-18, 15 September 2024), and locked prior to the start of participant recruitment and data collection. No outcomes were added, removed, or modified after data inspection, and no post-hoc analyses were conducted beyond those pre-specified in the protocol. The manuscript adheres fully to the TREND reporting standards for non-randomized evaluations.
The commitment of health personnel in initiatives for improving their working conditions is recognised as a key condition for the success and the sustainability of such initiatives. Healthcare organisations are faced with the challenge of deploying strategies needed to mobilise this commitment. The objective of this article is to present the results of a qualitative evaluation of a bottom-up co-construction project aimed at engaging oncology staff in four Québec healthcare organisations in a process of transformation and improvement of their working environment. As part of our constructivist approach, we utilised a qualitative method, which involved conducting one-on-one interviews and gathering documentary data, including survey results, to assess the development and implementation of an intervention across four oncology units. We conducted one-on-one interviews from January 26, 2023 to March 5, 2023 with 17 workers from different categories. We collected documentary data that cover the pre-implementation activities, the co-construction workshops, and the intervention implementation. All collected data were coded and analysed using QDA Miner 6.0, and our findings were validated iteratively throughout the project, involving regular interaction with participants. Fourteen areas of vulnerability emerged across the four dimensions studied, and six were targeted by workers as priorities: emotional exhaustion; role conflict; ability to learn; leadership; team cohesion; and communication. Interventions developed to address the prioritised areas included: co-development workshops; training sessions aimed at enhancing workers' control over their working environment; team connectivity through professional and social activities; staffing and workload reviews; support from a psychosocial professional; and coaching. According to workers, most improvements occurred in two targeted areas, team cohesion and communication, even in the units where these issues were not prioritised at first. Participants pinpointed some factors that facilitated the implementation of the intervention and its impact (engagement, organisational support, the bottom-up approach) and others that created constraints (staff shortages, conflicting priorities, level of commitment). This exploratory work offers insightful perspectives on how a bottom-up co-construction approach can serve as a lever to engage workers to improve their work experience. It may inspire other healthcare organisations, both in oncology and in other fields of activity.
Objectives. Proper use of personal protective equipment (PPE) is essential for worker safety, but many employees fail to use it correctly due to limited knowledge, negative attitudes and low perceived control. This study assessed the effectiveness of a health belief model (HBM)-based educational intervention on PPE use among factory workers in Yasuj. Methods. This quasi-experimental study (2022-2023) randomly assigned 109 workers were to experimental (n = 56) and control (n = 53) groups. The intervention included six 60-min in-person sessions delivered by a researcher and an occupational health expert. Data were collected via an HBM-based questionnaire before and 2 months after the intervention. Statistical analyses included paired t tests, independent t tests and χ2 tests using SPSS version 27. Results. Pre-intervention assessments showed no significant differences between groups (p > 0.05). Post intervention, the experimental group demonstrated significant improvements in all HBM constructs - knowledge, attitudes, perceived susceptibility and severity, perceived benefits and barriers, self-efficacy, guidance for action - as well as PPE-related behavior (p = 0.001). Conclusion. HBM-based educational interventions effectively enhance PPE usage by improving knowledge, shaping positive attitudes and addressing perceived barriers and benefits. These findings support structured educational programs as a key strategy for promoting workplace health and safety.
The role of age diversity has increased attention in organizations with the focus of collaboration between younger and older employees. The present study aims to investigate the perceptions of younger generation towards others with respect to organizational commitment, trust and job satisfaction in the healthcare field, particularly in nursing. A quantitative survey was conducted to collect data from 696 working young professionals in nursing within the healthcare sector in Pakistan. Structural equation modeling was employed to examine the relationships among the variables using Smart-PLS Software version 4.1.0.9. The obtained results show that the perceptions of working professionals from Generation Z with respect to generational stereotyping, positive effect and inclusiveness about other generations are positively correlated with trust and job satisfaction by mediating role of organizational commitment in the nursing sector. Research highlights perception of Generation Z at workplace impacted on trust, satisfaction, and commitment and closely connected to improved quality of work life. The study contributes to the existing literature on nursing management of intergenerational interactions. It advocates for redesigning systems to focus on development and well-being within the nursing sector.
Los Angeles County-wide criminal justice reform and policy decision-making focused on reentry and diversion from incarceration usually include only the voices of law enforcement and other public-sector employees, with little input from impacted community members. The Reentry Health Advisory Collaborative (RHAC), founded in 2020 with grant funding, was established to engage formerly incarcerated individuals and their communities in county safety-net health systems. We aimed to assess the impact of RHAC and the importance of formerly incarcerated community input in safety-net programs and policymaking. In 2022, following 3 years of RHAC implementation, online qualitative surveys were conducted with RHAC members and reentry service collaborators, including agency staff, nonprofits, and policymakers, to understand RHAC's influence and how lived experiences inform justice and health systems. Thirty replies from collaborators (59%) and eight from members (100%) resulted in thematic findings that highlighted benefits of involving formerly incarcerated persons in program and policy decisions-such as their firsthand experiences, focus on root causes, and community and socioeconomic tailoring approaches-and challenges like limited political power, varying receptiveness to ideas and inclusion, and a lack of sustainable funding. Members shared outcomes like motivation, peer support, leadership skills, and advocacy training needs. Recommendations for future inclusion emphasized promoting awareness and strategies for relationships with public-serving institutions, early inclusion for impacting pivotal decision-making, and continued engagement with the community through on-the-ground grassroots efforts. Barriers to reentry included basic needs, access issues, lack of support, and discrimination. Compensating lived experience in health and justice services promotes inclusive, equitable policies that reflect community needs.
Variability in the clinical presentation of patients with type 2 diabetes (T2D) is high and underlines the need for more personalized patient care. This nationwide study aimed to describe characteristics, treatment patterns, and disease progression of Finnish patients with T2D (N = 302,987), and to identify patient clusters with distinct progression patterns based on the occurrence of diabetes-related complications. The study included all adult patients with incident T2D in Finland between 2010 and 2019. Data were collected from national health and social care registers, data lakes, and a private healthcare provider between 1996 and 2021. Patient clusters were identified based on disease progression, defined by the occurrence of 22 pre-defined end-points, using likelihood-based growth mixture modeling. Five patient clusters with stable (C1; n = 133,951), mild (C2; n = 52,819), moderate (C3, n = 43,488), rapid (C4; n = 10,159), and extremely rapid progression (C5; n = 1973) were identified. The mean number of end-point complications per patient at baseline ranged from 0.2 to 2.3 across clusters and remained stable in C1-C3 over the first 5 years. In C5, the number increased to 5.5 and 7.2 during the first and third follow-up years, respectively, with a similar but more modest annual increase observed in C4. Cardiovascular complications increased more rapidly in C5 and C4 than C1-C3. T2D medication use was more common in milder clusters, whereas 31.4% and 48.2% of patients in C4 and C5, respectively, had no T2D medication. The rate of certain infections and values of creatinine, hemoglobin, and erythrocytes, increased with cluster severity. Diagnosis of several other new conditions, particularly cardiovascular complications, at or soon after incident T2D diagnosis predicts poor prognosis. The results further support a comprehensive approach in diabetes care, including evaluation and treatment of cardiovascular diseases alongside glycemic control. It is well known that people with type 2 diabetes can experience the disease in different ways, with wide variation in symptoms and disease progression. To support more personalized care, clinically useful tools that can predict how the disease will develop are needed. The researchers analyzed nationwide health register data from Finland, including all patients who received their first diagnosis of type 2 diabetes between 2010 and 2019. Their goal was to group patients into clusters with different long-term disease progression patterns, based on the development of diabetes-related complications after diagnosis. In total, the study included 302,987 patients with type 2 diabetes. These patients were divided into five clusters showing either stable (cluster 1), mild (cluster 2), moderate (cluster 3), rapid (cluster 4), or extremely rapid (cluster 5) disease progression. Further analysis showed that having additional conditions diagnosed at, or shortly after, the onset of diabetes was linked to a worse prognosis. Notably, 18.6% of patients did not purchase any diabetes medication during the follow-up period. This proportion was particularly high in patients allocated to cluster 4 (31.4%) and cluster 5 (48.2%). This study shows that patients with type 2 diabetes can be classified into meaningful groups with different progression patterns. This approach may help clinicians make timely and cost-effective decisions, focusing resources on patients most likely to benefit from early and intensive treatment.
Recent trial data support the use of the Impella heart pump for the management of patients with cardiogenic shock (CS). However, questions regarding the cost-effectiveness of Impella compared with alternative mechanical circulatory support (MCS), such as venoarterial extracorporeal membrane oxygenation (VA-ECMO), affect adoption. In this study, we evaluated the cost-effectiveness of Impella versus VA-ECMO among patients requiring MCS for CS, from the perspective of the Australian healthcare system. A survival analysis was constructed to estimate cost-effectiveness. Survivors were assigned costs and outcomes over a lifetime time horizon. Clinical inputs were derived from a meta-analysis of propensity score-matched studies comparing Impella with VA-ECMO. Health care resource use and unit costs were included consistent with the Australian health care system perspective. Utility weights were applied to surviving patients to calculate quality-adjusted life-years (QALY), and both costs and outcomes were discounted at an annual rate of 5%. In the base-case, Impella was associated with cost savings of Australian dollars (AUD) $30,157 per person, 2.798 additional life years, and 1.206 additional QALYs compared with VA-ECMO. At a willingness-to-pay threshold of AUD $50,000 per QALY, the estimated net monetary benefit was AUD $90,450. Sensitivity analyses demonstrated that results were most influenced by short-term mortality, daily hospital costs, and length of stay. This cost-effectiveness analysis and economic modelling suggests that targeted use of Impella represents a cost-saving technology compared to VA-ECMO for the management of CS, which may offer both clinical and economic benefits from the perspective of the Australian healthcare system.
The diagnostic accuracy of nicorandil for fractional flow reserve (FFR) measurement has been validated, whereas data on outcomes of FFR-guided revascularization strategy using nicorandil remain limited. This study aimed to compare clinical outcomes following FFR-guided strategy using nicorandil versus conventional hyperemic agents, such as adenosine or papaverine. From the J-PRIDE registry, 2369 patients (3295 lesions) and 831 patients (1009 lesions) were classified into the nicorandil and non-nicorandil groups, respectively. The primary study endpoint was the cumulative 1-year incidence of target vessel failure (TVF; a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization) on a lesion basis. Patients with multivessel disease, aortic stenosis, and severe angiographic stenosis were more likely to receive nicorandil. Overall, the cumulative 1-year incidence of TVF did not differ significantly between the nicorandil and non-nicorandil groups (3.2% versus 2.4%; adjusted hazard ratio [aHR]: 1.23; 95% confidence interval [CI]: 0.78-1.94; P = 0.37). Similarly, in both the deferred and revascularized population, the 1-year TVF rate was comparable between the two groups (2.9% versus 2.5%; aHR: 1.07; 95% CI: 0.62-1.86; P = 0.80; 3.6% versus 2.1%; aHR: 1.35; 95% CI: 0.58-3.11; P = 0.48, respectively). A significant interaction was observed only between the effect of nicorandil on TVF and hemodialysis (P for interaction = 0.028). The 1-year TVF rate was comparable between the nicorandil and non-nicorandil groups, supporting the clinical applicability of nicorandil for FFR measurement in clinical practice.
The interest in therapeutic applications of tetrahydrocannabivarin (THCV) recently increased. For this reason, we validated an online extraction liquid chromatography- tandem mass spectrometry (LC-MS/MS) method to investigate the formation of urinary metabolites and understand potential cross-reactivity of THCV metabolites in cannabinoid immunoassays. Urine samples were obtained after oral administration of Δ8-THCV to healthy participants. The protocol was approved by the Advarra Institutional Review Board (Pro00059879; approved December 20, 2021) and the trial was registered on clinicaltrials.gov (NCT05210634). Urine samples were collected pre-dose and pooled 0-8 hours post-dose. Urine samples were extracted using a simple one-step protein precipitation procedure and the extracts analyzed using online trapping LC-MS/MS in positive multiple reaction monitoring mode. All compounds passed validation criteria in urine. In the clinical samples, 11-nor-9-carboxy-Δ8-THCV (Δ8-THCV-COOH) was the main metabolite detected before and after incubation with glucuronidases. Of the urine pooled 0-8 hours post-dose, 70 out of 80 were reported positive by a cannabinoid immunoassay targeting Δ9-THC-COOH, despite being negative for Δ9-THC-COOH and positive mainly for Δ8-THCV-COOH in the LC-MS/MS analysis. The major metabolites of Δ8-THCV in urine were Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH that were extensively glucuronidated and cross-react with immunoassay routinely used for toxicology testing resulting in false positive results for Δ9-THC exposure.
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Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals widely used in industrial applications and consumer products, which have been associated with negative health outcomes, including cancer. Comprehensive identification of highly exposed occupations is needed. We aim to examine serum PFAS concentrations across occupation and industry of employment and other exposure determinants in a national sample of adults in the cross-sectional Canadian Health Measures Survey (CHMS). Serum concentrations of six PFAS compounds (perfluorooctanoic acid [PFOA], perfluorooctane sulfonate [PFOS], perfluorohexane sulfonate [PFHxS], perfluorononanoic acid [PFNA], perfluorodecanoic acid [PFDA], and perfluoroundecanoic acid [PFUnA]) were measured in a total of 5956 participants (ages 20-79 years) from four cycles of the CHMS (2007-2019). Multivariable linear regression models were used to predict geometric means (GM), adjusted for demographic, dietary, and environmental determinants. Adjusted geometric mean ratios (GMR) and 95% confidence intervals (CIs) for each exposure determinant vs. its reference group, and each of the 152 occupation or industry groups vs. all other participants, were estimated overall and by sex. PFAS concentrations declined substantially over time and were elevated among participants who were older, male, or East/Southeast Asian. GMRs for various PFAS were elevated in healthcare, assembly manufacturing, and agriculture occupations. Overall, laborers in manufacturing had 21-25% higher GM serum concentrations of PFOA, PFOS, and PFHxS, while those employed in the clothing manufacturing industry had two-fold higher PFOS (GMR = 2.39, 95%CI: 1.53-3.73) and PFHxS (2.12, 1.18-3.82). Females in front-line public protection had elevated PFOA (1.56, 0.99-2.46), and females in industrial, electrical and construction trades had 87% higher PFHxS. PFAS exposure was elevated in several occupations and industries with known or plausible sources of occupational exposure, with some important differences by sex. Further targeted assessment is needed to identify and mitigate exposure in highly exposed groups. This Canadian cohort analysis advances the understanding of occupational exposure to PFAS by identifying several novel occupational groups with validated elevated serum PFAS concentrations, including healthcare; construction trades; laborers and assemblers in manufacturing; clothing manufacturing; and electrical manufacturing, alongside more established groups such as chemical manufacturing and front-line protection. Among females, a historically understudied group, elevated levels were observed among front-line protection; construction trades; manufacturing supervisors and operators; and specialty trade contractors. To our knowledge, this is the first population-based study to investigate sex-stratified PFAS biomarker concentrations among adults employed in a wide range of occupations and industries.
Disease models are used to evaluate drug candidates, and compounds that are highly effective in vivo models have traditionally been prioritized for development. While conventional 'gold standard' animal models have been central to autoimmune drug discovery, there is increasing recognition that addressing unmet medical needs requires models capable of capturing patient pathophysiology beyond the scope of these classical systems. Accordingly, models that reflect human disease mechanisms not reproducible in conventional animals are becoming increasingly important. Humanized mice are immunodeficient mice transplanted with human immune cells, hepatocytes, thymic tissue, and other components to create a human-like biological environment that cannot be replicated in wild-type mice. Research on humanized mice has advanced through efforts to reconstitute a diverse human immune system in mice, together with accumulating knowledge of patient-specific factors such as autoantibodies and autoreactive T cells. Additionally, single-cell analyses and human tissue studies are underway to recreate the human-specific disease phenomena in humanized mice. In this review, immune-system-humanized mice are used to provide a comprehensive overview of recent advances in immune-system-humanized mouse technologies, their applications to immune-related disease models, and their current utilization in drug discovery research.
Occupational and environmental risk factors for salivary gland cancer (SGC) are largely unrecognised. This systematic review is the first to characterise the relationship between employment in specific industries or occupations and risk of SGC, as well as exposure to key occupational and environmental hazards.Studies published up to September 2023 were collected from three electronic databases and systematically screened. The Health Assessment Workplace Collaborative programme was used to tag studies based on pre-established inclusion and exclusion criteria. Studies eligible for inclusion (n=24) underwent an in-depth review to extract key study characteristics and findings, including effect estimates and 95% CIs. Studies were evaluated for influence of key biases. To identify priority sectors and hazards for intervention, effect direction plots were created to analyse the number and quality of studies reporting elevated rates of SGC across industry, occupation and exposure groups.24 articles were included for analysis. Exposure misclassification and confounding bias were a common concern across studies. Industry and occupation groups with the strongest relationship to SGC included cleaning services, material handling, food services, rubber/plastics production, engineering and construction/painting. Exposures with the strongest relationship to SGC included silica dust, cement dust, chlorinated solvents, formaldehyde and white spirits.Several occupational exposures were associated with an elevated risk of SGC, whereas environmental evidence was more limited. Additional research involving larger cohorts with quantitative exposure data is needed to further establish relationships between occupational and environmental exposures and often-overlooked rare cancers like SGC.PROSPERO registration number: CRD42023468037.
Immune responses elicited by natural infection of the coronavirus SARS-CoV-2 (COVID-19) show significant heterogeneity in the magnitude and quality of memory T and B cell responses. However, little is known about the contributing factors. In this study, we investigated the early immune factors that contribute to this variability using RNA-seq, targeted proteomics, and flow cytometry analyses. Specifically, we sought to investigate associations between early immune responses and SARS-CoV-2 memory immunity in a longitudinal cohort of 46 individuals hospitalized for COVID-19 from May 2020 to March 2021. These participants returned for follow-up visits up to one-year post-hospitalization where we characterized antibody titers, antibody neutralization, antibody durability, and cellular memory T and B cell responses with multiple assays. Additionally, using integration analysis of Omic measurements, we identified common genes, proteins, and cellular pathways associated with differential memory response outcomes. Our data suggests that high levels of inflammatory proteins, and co-stimulatory molecules during the early stages of COVID-19 lead to enhanced memory T and B cell responses and improved durability. Alternatively, molecules that have a negative effect on dendritic cell maturation including TNFSF11 and FLT3LG correlated with suboptimal memory immune responses. Importantly, we were able to identify early markers that are positively and negatively associated with durable antibody responses in infected participants. This study provides a unique and thorough examination of both innate and memory immunity in the same patients over time, offering valuable insights into the long-term durability of SARS-CoV-2 immunity.
Aleniglipron is an oral, small-molecule glucagon-like peptide-1 receptor agonist (GLP1-RA) in development for obesity treatment. The ACCESS phase 2b placebo-controlled, double-blind study randomized 230 adults (mean BMI 39.5 kg m-2, 54% female) with obesity or overweight to examine the effects of once-daily aleniglipron escalated every 4 weeks to 45, 90 or 120 mg. At week 36, the trial met its primary endpoint with a placebo-adjusted LS mean (95% confidence interval) body-weight change from baseline of -8.2% (-11.1 to -5.3%), -9.8% (-12.5 to -7.2%) and -11.3% (-13.9 to -8.6%) for the aleniglipron 45-, 90- and 120-mg arms, respectively (P < 0.0001, all doses versus placebo), with no apparent weight-loss plateau at the end of the double-blind period. Continued weight loss was observed at the interim analysis (median treatment duration of 20 weeks) of the ongoing open-label extension. Gastrointestinal events were generally mild to moderate and decreased in frequency over time, with little to no recurrence of vomiting after reintroduction following permitted dose interruptions. Treatment-related discontinuations were 10.4% across aleniglipron arms, with no events of drug-induced liver injury. Clinically relevant weight reductions of up to 11.3% with a tolerability profile consistent with the GLP-1RA class support further development of aleniglipron for obesity treatment. ClinicalTrials.gov registration: NCT06693843 .
Lack of access to rehabilitation perpetuates health inequities in equity-denied groups, but evidence on populations most affected by inequitable access to rehabilitation is fragmented. We conducted a scoping review using the Joanna Briggs Institute methodology to identify groups experiencing inequities, barriers to access, the methods used to study (in)equitable access and the interventions used to address it. We searched MEDLINE (via Ovid), Embase (via Ovid) and CINAHL (via EBSCOhost) for studies investigating equitable access to rehabilitation. We screened titles, abstracts, and full texts against predefined eligibility criteria. Out of 3,674 articles identified, 209 studies met the inclusion criteria. Data were extracted on study characteristics (e.g., country of origin), target populations, methodology, barriers to access, and intervention types. The extracted data were organized and categorized using the PROGRESS-Plus equity framework and the Candidacy 2.0 conceptual framework. The majority of included studies were conducted in the USA (n=115), Australia (n=32), and Canada (n=26). Most included studies compared access between groups (e.g., Black/White) (n=130), explored barriers to access (n=26), or examined the impact of rehabilitation policies (n=22). The most commonly reported barriers were the cost of services (n=12) and transportation (n=11). There is an abundance of literature demonstrating disparities in access, with very little research focused on improving access. More robust data infrastructure, including data on structural determinants of health would provide a more nuanced understanding of access to rehabilitation for equity-denied groups.
Anti-programmed cell death-(ligand) 1 (anti-PD-[L]1) agents are approved for advanced and early-stage cancers. While they may offer clinical and economic benefits in the neoadjuvant and/or adjuvant setting, their population-level impact in Italy has not been thoroughly evaluated. This study aims to estimate health and productivity outcomes of introducing anti‑PD‑(L)1 agents for neoadjuvant and/or adjuvant therapy in early‑stage cancers in Italy (melanoma Stage IIB/C, melanoma Stage III, renal cell carcinoma, triple‑negative breast cancer and resectable non‑small‑cell lung cancer) over a 10-year horizon. We developed a model synthesising outputs from five indication-specific Markov models comparing two worlds: one without anti-PD-(L)1 agents use in the neoadjuvant and/or adjuvant settings versus one with their use. Italian-specific population and incidence inputs were used, with clinical and quality-of-life data from individual trials, from a societal perspective with 3% annual discount. Outcomes included total life years (LYs), recurrence- free (RF)/event-free (EF)/disease-free (DF) LYs, quality-adjusted LYs (QALYs), number of recurrences/events, metastatic treatments, total deaths and deaths after first event/recurrence. Productivity gains were estimated using a human capital approach. Between 2025 and 2034, 118,329 patients with early-stage cancer were estimated to be eligible for anti-PD-(L)1 agents in Italy. Compared with no early-stage use, neoadjuvant/adjuvant use was associated with increased total LYs (+ 20,458, + 5%), RF/EF/DF LYs (+ 60,631, + 19%), QALYs (+ 21,093, + 6%) and fewer recurrences/events (- 20,209, - 33%), metastatic treatments (- 25,220, - 38%), total deaths (- 7137, - 24%) and deaths after first event/recurrence (- 8021, - 32%). Productive years gained were 35,897 (+ 30%). Our study suggests that the use of anti-PD-(L)1 agents in early-stage cancers is associated with substantial health and societal gains in Italy. Expanding their use across approved indications translates trial benefits into fewer recurrences, deaths and productivity losses, informing national planning and access decision.
COVID-19 vaccination with updated compositions remains important as SARS-CoV-2 continues to circulate, cause disease, and evolve. Available COVID-19 vaccines in the 2024-2025 season differed by platform, including mRNA-1273, an mRNA-based vaccine, and NVX-CoV2705, a recombinant protein-based vaccine and antigen composition (KP.2-targeted and JN.1-targeted, respectively). Limited real-world evidence exists comparing effectiveness in preventing severe COVID-19 outcomes. We compared mRNA-1273 with protein-based NVX-CoV2705 in insured US adults vaccinated during the 2024-2025 season. We conducted a retrospective matched cohort study in a large US claims database. Adults aged 18 years or older who received mRNA-1273 ("exposed") or NVX-CoV2705 ("reference") between August 31, 2024 and February 28, 2025 were eligible. Recipients were matched 2:1 on key demographic and clinical factors and then weighted with stabilized inverse probability of treatment weights. Outcomes were medically attended COVID-19 and hospitalization with COVID-19 from day 7 after vaccination through up to 180 days of follow-up. We calculated comparative vaccine effectiveness (cVE) as 100 × (1 - hazard ratio). Of 1,156,441 mRNA-1273 recipients and 45,384 NVX-CoV2705 recipients, 69,140 and 34,570, respectively, entered the matched cohort. Median (Q1, Q3) follow-up was 180 (163, 180) days for mRNA-1273 and 180 (162, 180) for NVX-CoV2705. Medically attended COVID-19 occurred in 706 (1.02%) mRNA-1273 recipients and 512 (1.48%) NVX-CoV2705 recipients; adjusted cVE (95% confidence interval [CI]) was 31.7% (23.4%, 39.1%). Hospitalization with COVID-19 occurred in 61 (0.09%) and 49 (0.14%) recipients, respectively; adjusted cVE (95% CI) was 40.7% (13.5%, 59.4%). In the 47,754 mRNA-1273 recipients matched to 23,877 NVX-CoV2705 recipients aged ≥ 65, adjusted cVE (95% CI) was 25.7% (15.4%, 34.8%) against medically attended COVID-19 and 41.7% (14.3%, 60.4%) against hospitalization with COVID-19. In this insured US adult population, mRNA-1273 demonstrated greater effectiveness against medically attended COVID-19 and hospitalization with COVID-19 than the protein-based NVX-CoV2705. These findings highlight the potential public-health importance of considering vaccine platform and variant selection when planning for upcoming seasons.
Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by a deficiency of branched-chain ketoacid dehydrogenase, the enzyme involved in the second step of branched-chain amino acid catabolism. Of the three branched-chain amino acids (leucine, valine, and isoleucine), accumulation of leucine is the predominant factor causing acute metabolic decompensation in patients with MSUD. In February 2025, eight expert physicians met to discuss the management of acute metabolic decompensation and propose recommendations after literature review (four guidelines and 20 other articles of interest). A practical clinical algorithm was established. Newborn screening was acknowledged to be a successful method of diagnosing MSUD at birth, facilitating early intervention to prospectively manage MSUD and reduce the frequency and severity of acute metabolic decompensation, although it was noted that infants with severe MSUD often present with acute metabolic decompensation before being diagnosed. The experts also identified several barriers to and gaps in the management of acute metabolic decompensation, and MSUD more generally, proposing potential actions to improve clinical outcomes. Acute metabolic decompensation requires prompt, effective treatment by a multidisciplinary team to ensure that circulating plasma leucine levels are rapidly reduced without causing complications (particularly cerebral edema). Where available, intravenous branched chain amino acid-free solutions (e.g., Maapliv, now approved in Europe) may represent an important treatment option. Adequate resources (treatments, laboratory services, dialysis units) are essential for effective management of acute metabolic decompensation. Liver transplantation is an accepted viable option for the long-term prevention of acute metabolic decompensation in eligible patients. Research is ongoing into new treatment options for MSUD, such as gene therapy. Optimal management of acute metabolic decompensation in patients with MSUD requires prompt, effective treatment to reduce leucine levels without causing complications. A ready-to-use branched chain amino acid-free intravenous solution has been recently approved in Europe and research into new treatment options is ongoing.
Automated tools quantifying multiple sclerosis (MS) imaging biomarkers often require non-routine MRI sequences and lack MS reference data. We developed an open-source quantitative report (QReport) that integrates validated 3D T2-FLAIR quantification methods with multi-centre MS and healthy reference models, and presents outputs in a structured graphical report to support contextualised interpretation of clinically relevant biomarkers. 2516 cross-sectional 3D T2-FLAIR scans from people with MS (pwMS) and healthy controls (HC) were retrospectively collected from 14 centres within Magnetic Resonance Imaging in MS (MAGNIMS) and affiliated sites, as well as open-source datasets. Validated T2-FLAIR-based algorithms quantified total and regional lesion count (LC), lesion volume (LV), brain volume (BV), and brain age gap estimation (BrainAGE). Distributions in pwMS and HC were estimated using quantile regression. A QReport was designed to present biomarkers and reference models in graphical formats. Four neuroradiologists assessed agreement between QReport outputs and their visual assessment, and evaluated its usefulness, in 22 cases. We analysed scans from 1723 HC (age, mean ± SD: 54.5 ± 16.0; range: 18-75; F/M: 949/774) and 793 pwMS (age, mean ± SD: 43.0 ± 11.1; range: 18-75; F/M: 538/255) across 14 centres. The QReport presents single-subject measures contextualised against the 95th, 50th, and 5th percentile distributions in pwMS and HC, and includes BrainAGE. In 94% of evaluations, QReport outputs demonstrated Moderate-to-Complete agreement with visual assessment and were rated as useful in 82%. We developed an MS QReport requiring only 3D T2-FLAIR, integrating validated quantification algorithms and incorporating BrainAGE within a clinically interpretable framework.