Lung cancer is typically a cancer of the elderly, with a median age at diagnosis of 71, and more than one third of the people diagnosed with lung cancer are over 75 years old. Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of cancers, including lung cancer. ICIs targeting the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis, administered in the neoadjuvant setting, the adjuvant setting, or both, are currently the standard of care for resectable non-small-cell lung cancer (NSCLC) worldwide. These ICIs are commonly used in combination with platinum-based chemotherapy and have shown superior efficacy in patients eligible for curative surgery. The concept of immunosenescence, which refers to age-related changes in the immune system - particularly a decline in the efficiency of T-cell mediated responses - raises concerns about the benefits of ICIs in the elderly population. To assess the benefits and harms of ICI with or without chemotherapy compared to no treatment or placebo with or without chemotherapy given before surgery, after, or both in older adults diagnosed with NSCLC at the early resectable stage. We searched for all eligible randomised controlled trials (RCTs) in electronic databases (CENTRAL, MEDLINE, and Embase), trial registries (clinicaltrials.gov and the World Health Organization ICTRP), references of eligible studies, meeting abstracts of the main world conferences, and the Food and Drug Administration (FDA) and European Medicines Agency (EMA) websites. The search was up to 3 July 2025. We included parallel designed RCTs comparing ICI with or without chemotherapy versus no treatment or placebo with or without chemotherapy administered before surgery, after, or both for early-stage resectable NSCLC. We excluded studies comparing differential sequencing of ICIs or combinations of ICIs with alternate interventions (e.g. radiotherapy). Our critical outcomes were overall survival and grade ≥ 3 treatment-related adverse events. Our important outcomes were disease-free survival, event-free survival, pathological complete response rate, major pathological response rate, and health-related quality of life. Two review authors independently used version 2 of the Cochrane risk of bias tool for randomised trials (RoB 2) to assess bias in the included studies. We synthesised results for each outcome and pooled data where possible (using a random-effects model with DerSimonian and Laird methods for all outcomes; and the Mantel-Haenszel method for dichotomous outcomes). Where this was not possible due to the nature or the amount of data, we narratively summarised the results. Three authors independently assessed the certainty of the evidence, using the five GRADE considerations for each outcome. We included a total of 11 studies with 6788 participants, of whom 3152 were ≥ 65 years old (46.4% of all participants). We were also interested in those aged ≥ 75 years old but could not obtain the exact number of such participants in nine studies. The inclusion criteria were similar across studies: adults presenting with a resectable NSCLC (stages II to IIIB according to the eighth edition of the Tumor, Node, Metastasis (TNM) classification), with an Eastern Cooperative Oncology Group performance status score of 0 or 1. One study excluded people ≥ 70 years old. Six studies excluded NSCLC with known alterations in epidermal growth factor receptor and anaplastic lymphoma kinase genes. The following results relate to people ≥ 65 years old only. The term perioperative is used to label studies evaluating the administration of treatment before (neoadjuvant) and after (adjuvant) surgery. Overall survival at any time point (in all studies) Aggregated data from three studies (590 participants) showed that perioperative ICI probably results in little to no difference in overall survival compared to placebo or no treatment, with a hazard ratio (HR) of 0.88 (95% confidence interval (CI) 0.61 to 1.26) and moderate-certainty evidence (downgraded for risk of bias). Treatment-related adverse events ≥ grade 3 at any time point One study (39 participants) provided data indicating that perioperative ICI combined with neoadjuvant chemotherapy may result in little to no difference in treatment-related adverse events ≥ grade 3 compared to neoadjuvant chemotherapy alone, with a risk ratio (RR) of 2.75 (95% CI 0.38 to 19.83) and low-certainty evidence (downgraded for indirectness and imprecision). Disease-free survival at any time point Aggregated data from three studies (1403 participants) showed that adjuvant ICI probably slightly increases disease-free survival compared to placebo or no treatment (HR 0.85, 95% CI 0.73 to 0.99) with moderate-certainty evidence (downgraded for risk of bias). Event-free survival at any time point Aggregated data from seven studies (1531 participants) showed that neoadjuvant or perioperative ICI likely increases event-free survival compared to placebo or no treatment (HR 0.61, 95% CI 0.52 to 0.71) with moderate-certainty evidence (downgraded for risk of bias). Pathological complete response Aggregated data from six studies (1068 participants) showed that neoadjuvant or perioperative ICI may result in a large increase in pathological complete response rates compared to placebo or no treatment (RR 5.07, 95% CI 3.40 to 7.54) with low-certainty evidence (downgraded for risk of bias and imprecision). Major pathological response Aggregated data from six studies (1068 participants) showed that neoadjuvant or perioperative ICI probably results in a large increase in major pathological response rates compared to placebo or no treatment (RR 2.94, 95% CI 2.32 to 3.72) with moderate-certainty evidence (downgraded for risk of bias). In people aged ≥ 65 years old, the addition of ICIs probably results in little to no improvement in overall survival. Based on one study, treatment-related adverse events showed a similar profile, with low-certainty evidence. However, ICIs probably increase disease-free survival, event-free survival, and major pathological response rates by a clinically meaningful margin. ICI may also increase complete pathological response rates. No study reported health-related quality of life assessments in older adults. Data were also insufficient to evaluate outcomes precisely in participants aged 65 to 75 years, those ≥ 75 years, or in PD-L1 stratified subgroups. We classified 12 studies as ongoing, as no results are yet available for elderly participants. This Cochrane review had no dedicated funding. Protocol available via DOI: 10.1002/14651858.CD014907.
This paper deals with the characterization of outdoor swimming pool waters to study the occurrence of trihalomethanes (THMs) and to assess the health risk of THMs exposure for three population groups (male, female, and children). The concentration of total THMs and individual species (chloroform, bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform) were monitored during the seven months of 2022 in outdoor swimming pools in the coastal area of Montenegro. A total of 73 water samples from outdoor swimming pools were collected and tested for the content of THMs using an Agilent 7890 A GC. Carcinogenic and non-carcinogenic health risks of total THMs and each species were assessed through lifetime cancer risk (CR) and hazard index (HI), respectively. Health risk assessment was assessed through the oral and dermal exposure pathways. The concentration of total THMs in investigated water samples ranged between 0.19 and 237.18 μg/L when 26% of tested water samples had values above the maximal permitted value (100 μg/L) established by Montenegrin legislation. Chloroform concentration was in a range of 1.13-217.16 μg/L, while contents of BDCM and DBCM were in a range of 1.01-29.43 μg/L and 0.18-16.19 μg/L, respectively. Calculated values of dermal CR were higher than 10-6, thus CR values of total THMs exposure were higher than 10-6 for all population groups. On the other hand, CR via ingestion values were meagre, HI values of total THMs exposure for three population groups were calculated to be below 1. There is no non-carcinogenic risk for the children population while male and female populations were faced with non-carcinogenic health risk of total THMs exposure. On the other hand, all investigated population groups were faced with unacceptable cancer health risks and dermal contact was recognized as the main exposure route for all investigated populations.
This study assessed perceptions of health and science students and academic staff regarding the health risks, environmental impact, and regulation of dental amalgam (DA). As DA faces increasing restrictions, understanding the views of students and academic staff is essential for evaluating educational and policy readiness. A cross-sectional survey was distributed to 1,230 participants in the Czech Republic. The questionnaire explored awareness of mercury exposure from DA, health and environmental concerns, and familiarity with regulations. Responses were statistically compared across disciplines. Overall, 35.8% of respondents did not recognize DA as a mercury source, and 48.5% did not view it as a health risk. Most did not consider DA an occupational hazard for dental professionals. However, 55.3% saw it as an environmental pollutant. While 59.2% supported restricting DA use in pregnant women and 51.0% in children, only 22.0% supported a complete ban. Most respondents preferred composites for aesthetic reasons (88.5%) rather than health concerns. Dental students differed significantly from other groups in several key areas, particularly regarding perceived health risks and support for restrictions on dental amalgam use. Perceptions of dental amalgam differed according to educational background. While most participants supported restricting its use in vulnerable populations, dental students were less likely to perceive it as a significant health risk and were less supportive of a complete ban. These findings highlight the importance of evidence-based education and public health communication regarding dental amalgam and mercury-related issues.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
to describe the garbage codes (GCs) identified in the Global Burden of Disease Study (GBD) 2023 and their redistribution to underlying causes of death in Italy in 2021. Specifically, the study aims to: 1. compare temporal trends in the proportion of GCs in Italy with those of other Western European countries with similar population sizes; 2. identify the most frequent GC packages, analyze their geographic distribution, and determine the causes to which they are reassigned; 3. examine the relationship between the proportion of GCs and contextual factors related to death certification, including the type of certifier, place of death, and requests for autopsy. descriptive epidemiological study based on GBD 2023 estimates. the analysis focuses on the Italian population in 2021, stratified by 21 subnational units, including 19 regions and 2 autonomous provinces. total number of deaths; number of GCs, defined as deaths attributed to causes that do not represent underlying causes of death; percentage of GCs, calculated as the number of GCs divided by total deaths and multiplied by 100. the proportion of GCs in Italy gradually decreased over time, from 34.6% in 1990 to 28.8% in 2021. In 2021, the three most frequent GC packages at the national level were 'unspecified type of stroke' (4.28% of total deaths), 'unspecified type of diabetes' (2.44%), and 'heart failure, right or left' (2.38%). In the same year, the proportion of GCs was positively correlated with the share of deaths occurring at home (r 0.71; p <0.001), with missing data on the type of certifying physician (r 0.54, p=0.020), on place of death (r 0.77, p <0.001), and on autopsy requests (r 0.76, p <0.001). misreporting of causes of death arises from multiple mechanisms, reflecting errors of different nature and severity, with important implications for public health policies and health information systems. While redistribution methods are essential to produce comparable and policy-relevant estimates, improving data quality at the source remains a critical priority.
The aim of the study was to determine the incidence of COVID-19 infection among healthcare workers (HCWs) at Reina Sofia University Hospital (RSUH) in Cordoba, Spain, from the first to the sixth wave of the pandemic. Additionally, we analysed the characteristics of infections across different age groups, genders, professional categories, hospital services, and COVID-19 vaccination status. An observational, longitudinal, analytical, and retrospective study was conducted, considering characteristics of person, time, HCWs category, and diagnostic test. The results of the tests of RSUH HCWs between March 2020 and March 2022 were analysed. Socio-demographic and clinical data were collected from the Alert Network of the Epidemiological Surveillance System of Andalusia. The study included 6,794 HCWs, of whom 1,513 (22.3%) tested positive for COVID-19. The distribution of COVID-19 cases among HCWs across the six waves was as follows: first wave - 150 cases (9.9%), second wave - 597 cases (39.4%), third wave - 225 cases (14.9%), fourth wave - 24 cases (1.6%), fifth wave - 121 cases (8%), and sixth wave - 396 cases (26.2%). The mean age of confirmed cases was 46.32 years (SD = 11.53), with a lower infection risk among HCWs aged 61-70 years. Only 16.9% of cases had received two vaccine doses at the time of infection. Nursing was the most affected professional category (30%). COVID-19 infection risk varies by age and HCWs category, decreasing in older HCWs but increasing among residents and certain specialties. During the Omicron variant's dominance, vaccines seemed less effective in reducing transmission. Health education programmes for both patients and HCWs are necessary to limit the spread of the disease.
This analysis of the Slovak health system reviews developments in governance, organization, financing and delivery of care, health reforms and health system performance. Slovakia, a central European country with a population of 5.4 million, continues to face significant health and health care system challenges. Slovakia's health system is founded on universal coverage with compulsory health insurance, a broad benefits package and a competitive insurance model. Although life expectancy improved between 2000 and 2019, the COVID-19 pandemic reversed gains, and in 2023 Slovak life expectancy remained three years below the European Union (EU) average. Circulatory diseases and cancer are the leading causes of death, and noncommunicable diseases such as diabetes and mental illness are rising. Nearly one third of all mortality is linked to behavioural risk factors, including poor diet, high smoking rates, low physical activity and obesity. Slovakia's health care system features competition among three insurers - one state-owned (Všeobecná zdravotná poisťovňa, VšZP) and two private. Since major reforms in 2004, the system has decentralized responsibilities and adopted selective contracting to enhance efficiency. However, structural weaknesses remain, particularly in financial sustainability, accessibility and equity. Health spending from public sources was 8.3% of gross domestic product (GDP) in 2024, yet out-of-pocket (OOP) payments account for nearly 19% of expenditures, disproportionately burdening low-income households. Workforce shortages, especially in nursing and primary care, are worsened by emigration and an ageing staff. Urban-rural disparities persist, with modern infrastructure and specialized services concentrated in cities. Digital health advancements, such as the National Health Information System (NHIS), aim to modernize care and facilitate telemedicine, though implementation is uneven. Ongoing reforms target cost containment, infrastructure optimization and integration of long-term care (LTC). Key priorities include addressing regional disparities, improving workforce retention, reducing waiting times and enhancing eHealth adoption. Despite universal coverage, Slovakia must address persistent gaps in health outcomes, resource distribution and system resilience to meet the needs of its population.
In low- and middle-income countries like Serbia, improving access to healthcare is a central objective of social and development policy, closely linked to the Sustainable Development Goals, particularly SDG 3 (Good Health and Well-Being) and SDG 8 (Decent Work and Economic Growth). However, healthcare expenditure is still frequently perceived as a fiscal cost rather than as a productive investment. Serbia, an middle-income country with a predominantly publicly financed healthcare system, offers a relevant case for examining how expanding healthcare access is intertwined with domestic economic structures and inclusive development outcomes. Using national input-output tables for 2019, this study applies standard input-output modelling to estimate output, income, employment, and value-added multipliers associated with the Serbian healthcare sector. The analysis captures direct, indirect, and induced effects, enabling an assessment of how healthcare spending propagates through domestic supply chains and labor markets. The findings show that healthcare in Serbia generates significant economy-wide spillovers that extend well beyond service provision. Output multipliers exceed unity, indicating strong domestic production linkages that support the availability and affordability of healthcare services. Employment multipliers rank healthcare among the leading job-generating sectors, contributing directly to SDG 8 by fostering stable and locally anchored employment. Most notably, the total value-added multiplier places healthcare among the top ten sectors of the Serbian economy, underscoring its capacity to retain expenditure domestically and to reinforce the economic foundations necessary for sustained healthcare access. The results demonstrate that investments aimed at improving healthcare access simultaneously advance broader economic inclusion and sustainable development objectives. Comparative benchmarking with European economies reveals structurally consistent patterns in health-sector integration across income levels, while also highlighting country-specific differences in income and employment transmission. By empirically linking healthcare access to macroeconomic returns, this study provides evidence to support policy frameworks that treat health expenditure as a strategic investment for achieving SDG-aligned, resilient, and inclusive growth in low- and middle-income countries.
Background and Objectives: The SARS-CoV-2 pandemic disrupted oral and maxillofacial surgery (OMS) services worldwide because of the high aerosol-generating nature of head-and-neck procedures, restricted access to elective dental care, and systemic reallocation of hospital resources. Continuous longitudinal multi-year data covering both the pandemic and the post-pandemic phases from regional Romanian (and more broadly central and southeastern European) emergency centers remain scarce. We aimed to quantify the impact of the pandemic on OMS activity in a large Romanian regional referral center and to evaluate post-pandemic resilience. Materials and Methods: We conducted a retrospective single-center study of all inpatient admissions to the OMS Clinic of a tertiary emergency hospital in western Romania between 1 January 2018 and 31 December 2024. Three periods were pre-specified: pre-pandemic (2018-2019), pandemic (2020-2022) and post-pandemic (2023-2024). A Newey-West segmented interrupted-time-series (ITS) regression and a negative-binomial monthly count model with Fourier seasonality were fitted; length of hospital stay was further analyzed with a multivariable gamma-log generalized linear model adjusted for age, sex, county, primary ICD-10 chapter and total ICD-10 codes. Variables analyzed included case volume, demographics, primary and secondary ICD-10 diagnoses, length of hospital stay (LOS), case complexity (total ICD-10 codes per admission) and in-hospital mortality. Results: A total of 11,628 inpatient admissions corresponding to 8084 unique patients (56.5% male; mean age 52.2 ± 19.2 years) were analyzed. Compared with the pre-pandemic baseline (mean 2037 admissions/year), annual volume dropped by 45.1% in 2020, 44.0% in 2021 and 32.3% in 2022, with a nadir of -76% during the first state of emergency (April 2020; n = 34 admissions). Recovery was rapid; 2024 exceeded the pre-pandemic baseline by +10.1% on raw counts and by +16.2% on admissions per 100,000 catchment population using year-specific INS denominators. The segmented ITS regression confirmed an immediate level drop of -114.2 admissions/month in March 2020 (95% CI -133.1 to -95.3; p < 0.001) and a positive post-intervention slope of +2.06 admissions/month (95% CI 1.23-2.88; p < 0.001), with observed monthly volume returning to the counterfactual projection by October 2023. The case mix shifted significantly (χ2 = 406.9, p < 0.0001); elective benign neoplasm admissions were reduced from 7.2% to 2.0%, while neoplasms of uncertain behavior nearly doubled from 15.7% to 27.5%. Case complexity increased during the pandemic (mean ICD codes 4.08 ± 2.42 vs. 3.44 ± 2.30; p < 0.001); after exclusion of administrative codes (whole Z chapter and U07.x), the difference attenuated to 3.34 vs. 3.17 codes (still p < 0.001 by Kruskal-Wallis), indicating that the largest portion of the unadjusted increase was driven by the new mandatory pre-admission SARS-CoV-2 screening code Z11.5 rather than true clinical complexity. Notably, the clinically interpretable proxy R63.3 (feeding difficulty) independently rose from 41.5% to 53.1%. The crude median LOS did not differ between the pre-pandemic and pandemic periods (3.07 vs. 3.06 d; p = 0.19) and dropped significantly post-pandemic (2.22 d; p < 0.001); however, after multivariable adjustment for case mix, age, sex, county and code count, the LOS was 15.7% shorter during the pandemic (adjusted ratio 0.84, 95% CI 0.82-0.87; p < 0.001) and 22.8% shorter post-pandemic (adjusted ratio 0.77, 95% CI 0.75-0.80; p < 0.001) relative to baseline. Conclusions: The pandemic caused a severe but transient contraction of OMS activity accompanied by increased case complexity and a marked shift away from elective surgery. Inpatient volume returned to and exceeded the pre-pandemic baseline by 2024. These results support the value of standing pandemic-preparedness protocols, sustained access to preventive dental care, and integrated tele-triage pathways for future public-health crises.
Work of an arborist - tree climbing - is a dangerous activity associated with great physical effort, influenced by incorrect body posture and significantly stressed individual parts of the body. This research was initiated with the objective to draw attention to this hitherto little explored issue connected with ergonomics of the work of tree climbers. The goal of the research was to gather information about the fatigue of individual parts of the human body in professional tree climbers who access trees using so-called rope techniques (ascent to the tree crown, movement in the tree crown, descent from the tree crown) by means of a questionnaire. The assessment included 12 body parts (8 in the upper body, 4 in the lower body), with each part being divided into right and left parts. The research was conducted in the Czech Republic, 98 respondents were professional tree climbers. The questionnaire contained two sections of questions. Questions from the questionnaire were analysed, evaluated and plotted into clear graphs which were then statistically quantitatively described. Furthermore, the linear relationship between the duration of work performance and the occurrence of fatigue in individual parts of the body was assessed (Pearson's correlation coefficients). Results indicated that the most stressed part of the body of tree climbers who access trees using rope techniques is the area of wrist and hands. On the other hand, the least stressed part of their body is lower leg. Furthermore, the results of Pearson's correlation analysis show that the relationship between the number of hours and the occurrence of musculoskeletal problems is weak, unstable, and nonlinear in most body segments. The research has shown that arborists who care for trees using rope techniques are exposed to varying degrees of fatigue in different parts of the body.
Pain, fatigue, and impaired health-related quality of life are common manifestations of rheumatoid arthritis. The aim of this study was to compare the effects of active conventional treatment with three different biological disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes after 48 weeks, in patients with early rheumatoid arthritis using data from the NORD-STAR trial. NORD-STAR was an investigator-initiated open-label randomised controlled trial done at 29 rheumatology centres across Denmark, Finland, Iceland, Norway, Sweden, and the Netherlands. Newly diagnosed patients aged 18 years or older, with rheumatoid arthritis (according to the 2010 American College of Rheumatology-European Allience of Associations for Rheumatology classification criteria for rheumatoid arthritis), symptom duration less than 24 months and who were naïve to DMARDs were randomly assigned (1:1:1:1) to receive active conventional treatment, certolizumab pegol, abatacept, or tocilizumab. The patient-reported outcomes assessed at baseline and weeks 4, 8, 12, 16, 24, 32, 40, and 48 included pain, patient's global assessment of disease activity, Health Assessment Questionnaire Disability Index, Fatigue, Short Form-36 (reflecting health-related quality of life, morning stiffness, and patient's acceptable symptom state). Linear mixed regression and logistic regression analyses were adjusted for sex, country, baseline patient-reported outcomes values, anti-citrullinated protein antibody status, and treatment group. Proportions of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) were assessed. There was lived experience involvement in the design and implementation of the study. This trial was registered with ClinicalTrials.gov, NCT01491815, and EudraCT, 2011-004720-35. Between Dec 14, 2012, and Dec 11, 2018, 812 patients were enrolled and randomly assigned; after exclusion of 17 patients not receiving tocilizumab due to administrative issues, the intention-to-treat population consisted of 795 patients (200 [25%] received active conventional treatment, 203 [26%] received certolizumab pegol plus methotrexate, 204 [26%] received abatacept plus methotrexate, and 188 [24%] received tocilizumab plus methotrexate). 547 (69%) of 795 patients were female, 248 (31%) were male, the mean age was 54 years (SD 15). Between baseline and week 48 large and clinically relevant improvements in patient-reported outcomes were observed in all treatment groups. At 48 weeks the biological DMARD groups had larger improvements in pain, fatigue, physical component score, and bodily pain of SF-36 compared with the active conventional treatment group. For pain, improvement exceeding MCID was reported by 155 (76%) of 203 patients with certolizumab pegol plus methotrexate and 162 (79%) of 204 patients with abatacept plus methotrexate compared with 136 (68%) of 200 patients in the active conventional treatment group. In the group of patients with tocilizumab and methotrexate 132 (70%) of 188 patients reported pain improvement exceeding MCID. The absolute differences between the biological DMARD groups and the active conventional treatment group were otherwise generally marginal. All treatment groups showed substantial improvements in patient-reported outcomes over time. Biological DMARDs produced somewhat greater gains in pain, fatigue, and physical quality of life measures than conventional treatments, though overall differences between groups were small. The results highlight that early treatment and effective disease control in rheumatoid arthritis lead to strong patient-reported benefits regardless of therapy type. Stockholm County Council, Swedish Medical Research Council, Swedish Rheumatism Association, Academy of Finland, Finska Läkaresällskapet, South-Eastern Health Region Norway, HUS Institutional grant, Icelandic Society for Rheumatology, Interregional grant from all health regions in Norway, NordForsk, Regionernes Medicinpulje, The Research Fund of University Hospital Reykjavik, UCB, Bristol Myers Squibb.
Convalescent plasma (CP) may reduce mortality in people with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks of this intervention is required. To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19. To identify completed and ongoing studies, we searched CENTRAL, MEDLINE, Embase, the Epistemonikos COVID-19 L*OVE Platform, and clinical trial registries to October 2024. We included randomised controlled trials (RCTs) evaluating convalescent plasma for people with COVID-19, irrespective of disease severity, age, gender, or ethnicity. We excluded studies investigating other coronavirus diseases or standard immunoglobulin. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality (up to day 28), worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life (QoL), grade 3/4 adverse events, and serious adverse events. We used RoB 2 to assess bias in included studies. We followed standard Cochrane methodology. We included 48 RCTs (24,518 participants), 15 of which were added in this update. We also identified 36 new ongoing studies and 33 completed studies awaiting classification. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease Forty-two RCTs investigated the use of CP for 21,393 participants with moderate to severe disease. Of these, 36 RCTs (20,798 participants) compared CP to placebo or standard care, five (604 participants) to standard plasma, and one (190 participants) to human immunoglobulin. In the full review, we performed subgroup analyses by antibody detection, time since symptom onset, country income level, and key comorbidities. Convalescent plasma versus placebo or standard care alone CP does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.90 to 1.03; 31 RCTs, 20,798 participants; high-certainty evidence). It has little to no impact on the need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.98 to 1.08; 8 RCTs, 15,189 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 9 RCTs, 13,930 participants; high-certainty evidence). CP may have little to no impact on QoL (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). CP may have little to no impact on the risk of grade 3/4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 6 RCTs, 2392 participants; low-certainty evidence). It probably has little to no effect on the risk of serious adverse events (RR 1.19, 95% CI 1.02 to 1.38; 11 studies, 5298 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma The evidence is uncertain about whether CP reduces all-cause mortality at up to day 28 (RR 0.77, 95% CI 0.53 to 1.10; 5 RCTs, 604 participants; very low-certainty evidence) and whether it increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 1 study, 34 participants; very low-certainty evidence). The evidence is uncertain about whether convalescent plasma reduces or increases the risk of grade 3/4 adverse events (1 RCT, 248 participants). The evidence is also uncertain about whether CP reduces the risk of serious adverse events (RR 0.82, 95% CI 0.57 to 1.17; 4 RCTs, 447 participants; very low-certainty evidence). No studies in this comparison reported clinical improvement or QoL. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease Six RCTs investigated the use of CP for 2761 participants with mild disease. Four RCTs (1164 participants) compared CP to placebo or standard care alone, and two (1597 participants) to standard plasma. Convalescent plasma versus placebo or standard care alone The evidence is uncertain about whether CP reduces all-cause mortality at up to day 28 (odds ratio (OR) 1.24, 95% CI 0.33 to 4.60; 3 RCTs, 1004 participants; very low-certainty evidence) and admission to hospital or death within 28 days (RR 0.45, 95% CI 0.04 to 4.81; 2 RCTs, 493 participants; very low-certainty evidence). It may have little to no impact on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 1 RCT, 376 participants) and on the risk of grade 3/4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 1 RCT, 376 participants), both with low-certainty evidence. The evidence is uncertain about whether CP has an impact on the risk of serious adverse events (RR 0.84, 95% CI 0.56 to 1.26; 2 RCTs, 494 participants; very low-certainty evidence). No studies in this comparison reported other critical outcomes. Convalescent plasma versus standard plasma The evidence is uncertain about whether CP reduces all-cause mortality at up to day 28 (RR 0.41, 95% CI 0.05 to 3.06; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.50, 95% CI 0.32 to 0.78; 2 RCTs, 1597 participants; moderate-certainty evidence). CP may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.82 to 1.54; 1 RCT, 416 participants; low-certainty evidence). Neither study in this comparison reported other critical outcomes. Compared with placebo or standard care, high-certainty evidence shows that CP does not reduce mortality in individuals with moderate to severe disease and has little to no effect on clinical improvement or worsening. CP probably has little to no effect on serious adverse events. Publication of ongoing studies might resolve some of the uncertainties around CP therapy for people with asymptomatic or mild disease. This review was previously a living systematic review, from the first version published in 2020 until our last search in October 2024. The research question is no longer a priority for decision-making, new studies are less frequently published, and research that might impact the conclusions of the review is no longer emerging. The European Commission, Belgium SUPorting high quality evaluation of COVID-19 convalescent plasma thrOughouT Europe (SUPPORT-E, grant number 101015756) supported this review. Protocol registered with the Center for Open Science on 17 April 2020 (DOI: 10.17605/OSF.IO/DWF53). Access the 2023 version of this review here: DOI: 10.1002/14651858.CD013600.pub6.
In Aotearoa New Zealand, human papillomavirus (HPV) self-testing was introduced simultaneously with HPV primary screening in September 2023 to improve access and reduce inequities for priority populations, including Indigenous Māori, Pacific and under-screened people. To contribute policy-relevant information, we implemented non-standard engagement and screening strategies, including text message invitation, mailed test kits, at-home self-testing, telehealth support and follow-up by a central nurse-led co-ordination team. We partnered with an Auckland primary health organisation (PHO) with high enrolment of priority populations. We invited people eligible for cervical screening aged 30-69 years by text message to receive mailed test kits (April-October 2023); people who did not respond were re-invited (October-November 2023). Offering a financial incentive to return a sample (intervention group) was compared with no offer (control group) in a sub-group of eligible Māori and Pacific who received a repeat mailed test kit in a nested randomised controlled trial (April-May 2024). Self-tested participants were invited by text message to an online survey. We invited 25,315 people and 24.0% opted in. Lower initial consent rates were increased after additional re-invitation reminders for Māori (20.0% to 30.4%) and Pacific (13.7% to 24.9%), with the final consent rate in Māori equal to European/Other (29.2%; p = 0.284). Almost half (48.2%) of consenting participants returned a sample, giving a self-test uptake of 11.6% (n = 2,925). Uptake was significantly lower (all p < 0.001) for Māori (12.7%) and Pacific (8.4%) vs. European/Other (19.0%), and for those under-screened (10.5%) vs. those overdue by < 6 months (19.4%). In the RCT, sample return rate did not differ significantly (p = 0.704) between the intervention (7.9%) and control (8.5%) groups. HPV was detected in 7.7% of 3,018 valid results. Follow-up test rates were high (96.8% for cytology, 90.5% for colposcopy). Almost all survey respondents preferred a mailed at-home self-test for their next screen (91.9%; n = 193 of 210). Invitation by text message to mailed at-home HPV self-testing engaged priority populations in cervical screening. Central co-ordination support achieved high rates of sample return and follow-up testing where required. A mailed at-home testing option, strongly preferred by survey respondents, warrants consideration in a broader programme to improve access to cervical screening, with additional targeted strategies to improve sample return rates for priority populations. While the overall study did not reach the ICJME or WHO criteria for clinical trial registration, the nested RCT was retrospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12625000798460) and World Health Organization (WHO UTN U1111-1324-8454).
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
Background and Objectives: Population ageing is a major challenge of the 21st century and is associated with declining physical and mental abilities, increased disease burden, and higher mortality. Latvia has the lowest healthy life expectancy in the European Union. Social well-being is an important component of healthy and active ageing and may be associated with older adults' quality of life (QoL). This study aimed to assess the relationship between social well-being, as a component of health, and QoL, including its components (control, autonomy, self-realisation and pleasure), among adults aged 50 and older in Latvia. Materials and Methods: Data from 1643 Latvian participants in wave 9 of the Survey of Health, Ageing, and Retirement in Europe (2022) were analysed using linear regression. QoL was measured using the 12-item Control, Autonomy, Self-Realisation, and Pleasure (CASP-12) scale. Social well-being factors included household composition, education, employment status, financial capacity, living area, social network (SN) characteristics, and received help, based on self-reported questionnaires. Results were considered statistically significant if the p-value was less than 0.05. Results: The factors positively associated with overall QoL were being employed, better financial capacity, greater satisfaction with SN, larger SN, participation in social activities, and higher educational attainment. Being employed and the ability to make ends meet easily were positively associated with all QoL components. Higher satisfaction with the SN and participation in social activities were positively related to the control, autonomy, pleasure, and self-realisation components. Conclusions: These findings underscore the importance of social and economic resources for QoL in later adulthood, suggesting that both the quality of social relationships and material security play a central role in shaping overall QoL and its components among older adults.
President Trump came into office with an agenda to rein in government programs and regulations. The Trump administration has focused on making government smaller and nearly eliminating humanitarian foreign health aid, while eschewing conclusions drawn by the mainstream scientific community, particularly regarding vaccination policy. Specific actions have included cuts to both health personnel and budgets, efforts to remove vaccine mandates, attempts to end diversity efforts, and the essentially shuttering of the United States Agency for International Development program. Reforms also include allowing the expiration of enhanced federal premium subsidies for the individual insurance marketplaces beginning in 2026 and a substantial reduction in federal payments to state Medicaid programs beginning in 2027. Downstream impacts will include collecting less health data, moving away from research on communicable diseases, promoting vaccine hesitancy, and reducing access to, and possibly the quality of, care. Cutting humanitarian foreign health aid may have an even larger impact, as access to vaccinations and medications has already been curtailed, especially in Africa. Cuts to global health have endangered lives in many of the world's poorest countries, while the destabilization of global trade has limited the scope for European countries to fill the gap. Millions of Americans will lose their health insurance coverage, while people in many countries - especially Africa - will have their lives endangered. Vaccination rates, particularly among young children, will decline, exposing more Americans to communicable diseases. Scientific research output is likely to decline as universities face increasing financial pressures.
The aim of the study was to assess potential health risks associated with a large-scale environmental release of benzene following a railway accident in Moravia, Czech Republic, in 2025, with emphasis on differences between population and occupational exposure. An assessment of potential health risks associated with exposure was performed using available environmental monitoring data. Conservative exposure scenarios were defined for the general population and for remediation workers. Non-carcinogenic risk was expressed as the hazard quotient (HQ), and carcinogenic risk as excess lifetime cancer risk (ELCR). Short-term peaks in ambient air benzene concentrations were observed in the period immediately following the accident and during remediation activities, with occasional hourly values reaching the order of tens of µg.m-3. During the accident and its immediate aftermath, benzene concentrations at the accident site ranged from < LOQ-32.3 mg.m-3 (LOQ - limit of quantification) in soil gas (March-April 2025), 0.0004-2.43 g.l-1 in groundwater (March-May 2025), < LOQ-19.9 µg.l-1 in surface water (March-June 2025), and < LOQ-849.7 mg.kg-1 in soils (March-April 2025). Extreme values were confined to the immediate accident zone and represented the dominant exposure for workers rather than residents. For the general population, HQ values remained below 1 and ELCR ranged from 10-6 to 10-5. In contrast, remediation workers exhibited substantially higher risks, with HQ values reaching 104-105 and ELCR up to 10-3, particularly for inhalation exposure. While population exposure remained within acceptable limits, occupational exposure during remediation represented the dominant health risk. Two workers involved in remediation activities were excluded from further work based on the results of biological monitoring of benzene exposure. The results highlight the need for strict exposure control and health surveillance of exposed workers.
This article analyses the institutional practices that shape socio-health care for cancer along the disease trajectory-from screening to survivorship-in five countries with the highest cancer survival rates: Australia, Belgium, Canada, Costa Rica, and Japan. Drawing on social practice theory, the study applies a critical documentary analysis of 115 institutional and scientific sources, including national cancer plans, legislation, and clinical guidelines, to examine how material elements, practical knowledge, and shared meanings are articulated in policy and practice. Findings reveal consistent patterns across the five high-survival countries, including the strong institutionalisation of screening programmes, continuous strengthening of diagnostic infrastructure, and establishment of interdisciplinary teams. However, significant challenges persist in addressing territorial inequalities, ensuring equitable access, and protecting patients from out-of-pocket costs associated with innovative therapies. Japan is distinguished by its population-based endoscopic screening for gastric cancer, while Australia and Canada lead in culturally adapted, community-based approaches. Costa Rica shows partial implementation through regional pilots, and Belgium displays high diagnostic and therapeutic integration with European networks. Psychosocial, financial, and legal support emerge as indispensable dimensions for achieving equitable and comprehensive cancer care. Non-governmental organisations and community networks play a central role in providing counselling, subsidies, and reintegration support, although their reach varies across contexts. Overall, the study underscores that biomedical innovation alone is insufficient: cancer survival depends on the effective coordination of biomedical, social, cultural, and legal policies within integrated socio-health care systems that prioritise equity and quality of life as key pillars of public cancer policy. In high-performing systems, survivorship is not merely the result of clinical coverage but emerges from an institutional ecosystem that bridges biological recovery and social citizenship.
In Central Europe, mushroom poisoning is a public health problem as the Czech Republic belongs to the countries with the highest proportion of mushroom pickers. The trends in A. phalloides intoxications, their treatment and outcome were investigated in verified cases, as several antidotes are recommended and their effect is still under discussion. Mushroom intoxications in 2010-2024 were searched in the database of the Czech Toxicological Information Centre (TIC) and the Institute of Health Information and Statistics. Intoxications with amatoxins in 2019-2024 were analysed. Mushroom-related consultations of TIC reached an average of 490 calls/year (SD = 130), and 190 subjects/year (SD = 36) were hospitalized. A total of 1,248 mycological identifications and laboratory analyses were performed in 2019-2024; in 45 proven intoxications with amatoxins, lethality was 4.4%. The amount of ingested mushrooms (0.3-8 pieces) was negatively correlated (r = -0.358, p = 0.041) with the latency to symptoms (10.4 ± 1.3 hours), and positively with the duration of hospital stay (7.8 ± 2.3 days, r = 0.356, p = 0.042), peak international normalized ratio (r = 0.445, p = 0.010), and use of elimination methods (r = 0.451, p = 0.008). Later admission correlated with alanine aminotransferase activity (r = 0.318, p = 0.033) and creatinine level (r = 0.447, p = 0.002). Patients with simultaneous amatoxin positivity of blood and urine had a longer hospital stay than those with only one positive sample (14.0 ± 6.6 vs. 7.4 ± 2.1 days, p = 0.018). Of 45 patients, 32 patients were treated with 2 or 3 antidotes; two patients died; an additional critical factor for lethal intoxications was preceding liver or psychic disorders. Eight patients received one antidote and recovered; there was no difference between N-acetylcysteine and silibinin (p > 0.05). Five patients with early admission were treated without antidotes and did not develop hepatotoxicity. Deaths from unintentional poisoning with amatoxins can be averted. Amount of mushrooms ingested, early treatment with N-acetylcysteine or silibinin, and evidence of amatoxins in blood and urine are key factors. Timely mycological consultations and information for safe mushroom collection, including for immigrants, are crucial.
Preventable medical errors are recognized as an important public health problem. The aim of this study was to evaluate the awareness of adults in the community about patient safety, medical errors and patient participation; and to determine their experiences of medical errors. Adults older than 18 years living in the Konya city centre in Türkiye were included in the study. The implementation of the questionnaire took approximately two months, and a total of 780 valid questionnaires were obtained. Participants were asked questions about their views and attitudes towards medical errors. In addition, participants' engagement in behaviours recommended by the Agency for Healthcare Research and Quality (AHRQ) to prevent medical errors was evaluated using a 4-point Likert scale. Twenty-six percent of the participants stated that they or one of their family members had suffered a medical error. Those who were exposed to the error (n = 201) mostly experienced physical problems (44.3%). Other reported consequences included psychological problems (19.4%), disability (10.9%), loss of employment (5.5%), and death (2.5%). When the answers given to the questions about exposure to medical error and "whether the patients are responsible for preventing the errors" were compared with the socio-demographic characteristics, a statistically significant difference was found between age, education status, socioeconomic status, and experiencing with medical error (p < 0.05). A significant part of the participants were harmed while receiving healthcare services. In addition, their awareness of protecting themselves from this harm was low. The findings of this study can guide healthcare professionals for patient safety training for patients.