搜索结果：Infectious diseases (London, England)

Invasive meningococcal disease (IMD) remains a rare but severe condition associated with high mortality and a significant risk of long-term sequelae. Despite global vaccination efforts, the epidemiology of Neisseria meningitidis continues to evolve, with serogroup B (MenB) representing the predominant cause of IMD in many high-income countries. This consensus document reviews current evidence on MenB epidemiology and the role of the multicomponent meningococcal serogroup B vaccine (4CMenB), with a focus on immunogenicity, strain coverage, real-world effectiveness, and remaining challenges. Protein-based MenB vaccines have overcome the limitations of polysaccharide approaches, demonstrating robust immunogenicity across age groups. Real-world data confirm substantial vaccine effectiveness, particularly in infant immunization programs and outbreak settings, with significant reductions in disease incidence. For example, in England in the 3 years after vaccine introduction, MenB IMD incidence declined by 75% in immunized infants compared to unvaccinated controls. Adjusted vaccine efficacy was 52.7% after the two-dose primary series and 59.1% following the booster dose, highlighting the contribution of the booster. However, protection is influenced by antigenic variability among circulating strains, resulting in incomplete and geographically variable coverage. In addition, antibody waning over time and the limited impact on nasopharyngeal carriage reduce the potential for long-term and indirect protection. These factors highlight the need to optimize vaccination strategies, including the timing of booster doses, particularly in adolescents, and the role of vaccination in different epidemiological contexts. In this regard, it is not precisely defined whether infants who were immunized in the first year of life need a booster dose in the preschool period, especially in countries with a high incidence of MenB disease. Moreover, it is not established whether and when adolescents who were vaccinated both in infancy and during the preschool period need a booster dose. Economic considerations and variability in national immunization policies further contribute to heterogeneity in vaccine implementation. Emerging evidence suggests possible cross-protection against other meningococcal serogroups and Neisseria gonorrhoeae, although findings remain inconsistent across different risk groups and do not allow us to recommend 4CMenB vaccine beyond MenB IBD prevention. 4CMenB is an effective tool for preventing MenB IMD, although further studies are needed. Future strategies should prioritize age-targeted boosting and enhanced genomic surveillance to maximize impact.

Irrespective of intensive global efforts to reduce under-five mortality, it remains a significant public health concern. Understanding the causes and trends of under-five mortality is essential for guiding targeted interventions, assessing the effectiveness of public health strategies, and monitoring changes in mortality over time. The health and demographic surveillance system is one of the preferred sources to study the cause of under-five mortality. This study aims to analyse the causes and trends of under-five deaths in Southwest Ethiopia using Gilgel-Gibe Health and Demographic Surveillance System (GGHDSS) database. GGHDSS is an open, dynamic cohort that was established in 2005. Fifteen years of mortality data and seven years of Verbal Autopsy (VA) data were extracted from the GGHDSS database for this study. The VA data are part of the fifteen year mortality dataset, in which causes of death were determined through the VA method. After extracting the data from MYSQL and OpenHDS, it was exported to Excel for further cleaning. Finally, the cleaned data were exported to R statistical software for analysis and visualization. Neonatal, infant, and under-five mortality trends were analysed and the proportion of cause specific deaths were identified from the VA data. Between 2005 and 2019, 28, 811 children, 13931 (48.35%) female and 14880 (51.65%) male, were born alive and registered in the GGHDSS, among which 1828 (6.34%) of them died before celebrating their fifth birthday. The overall under-five mortality rate was 63.4 (95% CIs; 60.6, 66.3) per 1000 live births while neonatal and infant mortality rates were 30(95% CIs; 28.1, 32) and 50.2 (95% CIs; 47.6, 52.7), respectively. The mortality rate during the surveillance years showed a declining trend among neonatal, infant, and overall under-five children, with average slopes of -2.49, -4.56, and -7.24, respectively. From 1070 under-five deaths captured by the VA method in GGHDSS during 2009-2016, 596 (55.7%) were male and 474 (44.30%) were female. The most common causes of neonatal death were birth asphyxia and perinatal respiratory disorders, bacterial sepsis, and prematurity including respiratory distress. In the post-neonatal period, the most common causes of death were acute lower respiratory infections (including pneumonia and acute bronchitis), intestinal infectious diseases including diarrheal diseases, and malaria. Severe malnutrition, intestinal infectious diseases, and acute lower respiratory infections were responsible for more than half of the deaths among children between 12 and 59 months of age. Under-five mortality has shown a significant declining trend between 2005 and 2019 at the study setting. Birth asphyxia, neonatal infections, and prematurity were among the most common causes of neonatal deaths, whereas infectious diseases and malnutrition were the main causes of death beyond the neonatal period. Strengthening perinatal and neonatal care, improving prevention and management of childhood infections, and enhancing early nutritional interventions are needed to reduce under-five mortality.

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This study investigated the impact of heat on the risk of hospital admission due to a range of health conditions in England. We used records of over 4 million hospital admissions in the summer months between 2008 and 2019, to construct daily time series of admissions in 32 837 census areas. Coupled with high-resolution environmental data, we conducted a case time-series analysis using distributed-lag non-linear models to measure the lagged relationship between summertime temperature and risk of admission for a broad set of health conditions. We derived the relative risks of admission at the 99th compared with the 50th temperature percentile to understand the effect of extreme heat in each locality. The adult population of England (aged 18 years and older). Unplanned National Health Service (NHS) in-patient hospital admissions for cardiovascular, respiratory, genitourinary, metabolic and infectious diseases, along with their subcategories. These conditions contributed more than 3.7 million admissions, of which over 1.5 million (42%) were for those aged 75 years and over. More than 80% of admissions were for respiratory, cardiovascular or genitourinary illness, which collectively contributed 3.1 million hospital admissions. There was clear evidence of an increased risk of hospital admission for many conditions, including acute renal failure (1.37, 95% CI 1.32 to 1.42), metabolic disorders (1.28, 95% CI 1.24 to 1.32), infectious and parasitic diseases (1.06, 95% CI 1.04 to 1.08), pneumonia (1.07, 95% CI 1.05 to 1.09) and chronic obstructive pulmonary disease (1.08, 95% CI 1.05 to 1.10). The evidence was less clear for asthma and diabetes, while there were negative associations for many cardiovascular conditions. There was a clear age gradient in heat-related admissions, with older people facing the greatest risk of admission. These findings highlight the widespread effect of extreme heat across a range of health conditions, in addition to mortality, and have implications for public health planning in our changing climate.

Cardiovascular disease (CVD) mortality is rising in Sierra Leone, but the health-system drivers of this trend are not well characterised. We mapped health-system barriers and facilitators for CVD care in Sierra Leone using a systems lens tied to universal health coverage (UHC). We conducted a scoping review following PRISMA-ScR guidelines. We searched MEDLINE, Embase, Scopus, Global Health, and African Journals Online (1 Jan 2000 - 10 May 2025), Of 498 unique records, we included 40 sources reporting CVD-relevant data. Findings were mapped to WHO health-system building blocks, and synthesised narratively. Our findings show a health system shaped by path dependence: investments in infectious disease programmes have strengthened vertical delivery platforms with limited integration of non-communicable disease services. Facility readiness averaged 41% for HIV services versus 16.8% for cardiovascular care. An urban risk paradox was identified: urbanisation increased the odds of hypertension (OR 1.46) and diabetes (OR 1.84), while primary care infrastructure remained more oriented toward rural maternal health. Service delivery was undermined by diagnostic gaps; limited access to neuroimaging for stroke was associated with a threefold increase in mortality. High out-of-pocket costs narrowed effective coverage toward wealthier groups, and recurrent medicine stockouts reinforced distrust and disengagement from formal care. Scalable enablers included task-sharing, digital tools, pooled procurement, and community engagement. Strengthening task-shared primary care, ring-fenced CVD budgets, pooling drug procurement, and improving digital infrastructure could accelerate UHC-effective coverage in Sierra Leone. Evidence on cost-effectiveness and socio-cultural determinants remains limited and should guide implementation research. Heart diseases are a major cause of death in Sierra Leone. However, the health system is still mainly designed to respond to infectious diseases including malaria and HIV, rather than long-term conditions like heart disease. In this review, we analysed 40 studies to understand why people often struggle to get proper heart disease care. We found that health facilities were much better prepared to deliver HIV services (41% readiness) than heart disease services (17% readiness). High blood pressure and other heart disease risks are increasing, especially with urbanisation. However, services for heart disease are not always available where people need them most. Many people still face long travel distances, limited services at nearby clinics, and poor availability of medicines, equipment, and trained staff. Unlike HIV care, heart disease care often requires out-of-pocket payments, which delays treatment until emergencies such as stroke happen. Solutions include adapting HIV infrastructure for heart disease care and lowering costs.

Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Recent reductions in global health funding have threatened TB control, making comprehensive assessment of TB, HIV-related TB, and drug-resistant TB burdens before these disruptions essential for shaping effective responses. The WHO End TB Strategy sets targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence between 2015 and 2035. Using results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, this study aims to assess the burden of TB and multidrug-resistant TB (MDR-TB) across 204 countries and territories, and to evaluate progress towards the WHO End TB incidence and mortality targets. We quantified TB mortality using the Cause of Death Ensemble modelling platform with global vital registration, surveillance, verbal autopsy, and minimally invasive tissue sampling data. For TB morbidity estimation, we simultaneously modelled incidence, prevalence, and mortality by age and sex using DisMod-MR 2.1. A population attributable fraction (PAF) approach was applied to stratify morbidity and mortality estimates by HIV and drug-resistance status. We also calculated disability-adjusted life-years (DALYs) as the sum of years of life lost and years lived with disability. For the risk factor analysis, a comparative risk assessment framework was used and PAFs were derived for alcohol use, smoking, and high fasting plasma glucose to determine the proportion of TB burden associated with these risk factors. In 2023, there were an estimated 9·11 million (95% uncertainty interval 8·04-10·3) incident cases of all-form TB, 1·22 million (0·98-1·49) deaths, and 54·6 million (43·8-65·5) DALYs globally. HIV-related TB comprised 781 000 (690 000-879 000) incident cases and 210 000 (142 000-279 000) deaths, contributing 11·0 million (7·56-14·3) DALYs. MDR-TB accounted for 466 000 (198 000-1 080 000) incident cases, 102 000 (31 700-238 000) deaths, and 3·96 million (1·31-9·01) DALYs. From 2015 to 2023, global all-form TB incidence rates declined by 19·2% (17·8-20·5) and deaths declined by 22·6% (4·7-35·7); declines were larger for drug-susceptible TB than for MDR-TB. Sub-Saharan Africa and south Asia had the highest mortality burdens in 2023; reductions in all-form TB incidence and mortality were uneven between 2000 and 2023, with limited progress in both measures in Latin America and the Caribbean. Removing smoking, alcohol use, and high fasting plasma glucose would reduce global TB deaths to 768 000 (592 000-970 000) and DALYs to 34·9 million (27·8-43·8) in 2023; MDR-TB deaths would decrease to 77 200 (23 400-183 000) and DALYs to 3·12 million (1·03-7·29). Global progress towards WHO End TB targets is disparate and fragile. Although many regions achieved meaningful gains, others have stagnated in recent years. The complexity of TB prevention is amplified by divergent MDR-TB trends, the persistent burden of HIV, and growing exposure to modifiable risk factors. Recent volatility in global health financing threatens to further destabilise this vulnerable epidemiological landscape; concerted action is urgently needed to temper disruptions and preserve progress. Gates Foundation.

Giardiasis is one of the most common enteric protozoal infections worldwide. It is frequently reported as an enteric parasitic infection in the United States of America (USA) and Europe, whereas reported incidence in Japan is substantially lower. This study characterized age-specific, geographic, and temporal patterns of reported giardiasis incidence in Japan, the USA, and Europe using publicly available surveillance data. This retrospective study analyzed surveillance data from the National Institute of Infectious Diseases (NIID) in Japan, the Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC) to describe epidemiological patterns, possible explanatory factors, and temporal trends before and during the COVID-19 pandemic. Annual trends were examined using all available surveillance years: 2007-2023 for Japan and Europe and 2007-2022 for the USA. Age-specific patterns were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods, and geographic patterns were examined using available regional data. Incidence rates in the USA and Europe were approximately 5 per 100,000 population, whereas reported incidence in Japan remained below 0.1 per 100,000. Age-specific patterns differed: incidence peaked in children aged 0-14 years in Europe, and in children aged 0-4 years and adults aged 25-39 years in the USA, whereas in Japan, incidence was highest among adults aged 25-44 years and relatively high among those aged ≥65 years. Geographic patterns also differed, with higher incidence in Tokyo, Nordic and Baltic countries and selected European countries, and New England and Midwestern states. Annual incidence was significantly lower in the COVID-19-onset period than in the pre-COVID-19 period across all regions. These findings suggest that exposure patterns and possible explanatory factors differ by region and age group, highlighting the importance of region- and age-specific prevention strategies.

Cerebral organoids (COs) are valuable for studying neurodegenerative diseases and pathogens, but their limited microglia pose challenges. Here, we present a protocol to generate organoids with physiologically relevant microglia (CO-iMs). We describe steps for differentiating induced pluripotent stem cells (iPSCs) into mesoderm, seeding embryoid bodies (EBs), and harvesting hematopoietic progenitor cells (HPCs). We detail procedures for co-culturing HPCs and iPSCs to generate CO-iMs, followed by their infection and treatment. The model provides a platform to study viral infections and neuroinflammation. For complete details on the use and execution of this protocol, please refer to Narasipura et al.1.

Although the availability of high-quality surveillance data is critical to inform efforts to reduce the major burden of bloodstream infections (BSIs), there remains a paucity of comprehensive population-based investigations worldwide. To describe the rationale and protocol development of the Queensland BSI (QBSI) study. Population-based laboratory surveillance was performed for all BSIs occurring in the publicly funded healthcare system in Queensland, Australia during 2000-2023. Linkages to statewide hospital admissions and vital statistics databases have been performed to determine clinical determinants and mortality outcomes for a minimum of 1 year post-BSI. Standardised definitions were developed to identify incident episodes of BSI and classify them according to type of onset. More than 3.7 million blood cultures were processed during the study period of which a total of 444,279 positive blood cultures were initially identified. Hospital registrations statewide within two years before index culture and one year after were included (n = 2,425,688 with 10,341,136 associated International Statistical Classification of Diseases (ICD) codes during 2000-2023). Comorbidities were classified using previously developed ICD-based algorithms for adults and children and all-cause case-fatality at 30, 90 and 365 days was chosen as the primary outcome measure. The QBSI study is an evolving program designed to comprehensively examine the epidemiology and outcome of BSIs occurring among residents of this large Australian state. Our aim is to share our experiences to support the development of collaborating centres elsewhere to accelerate epidemiology knowledge and ultimately reduce the major burden due to BSI in populations worldwide.

Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021-30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). In 2023, there were 50·9 million (95% UI 46·1-56·1) road injury incident cases, 1·34 million (1·04-1·58) deaths, and 75·3 million (59·8-89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10-39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9-39·7) and mortality decreased by 32·3% (6·1-49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7-56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1-7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9-947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. Gates Foundation.

To study the efficacy of fosfomycin trometamol (FT) as prophylaxis for recurrent urinary tract infections (UTI) in a population not targeted by guidelines. Retrospective, monocenter study of patients taking FT prophylaxis for recurrent UTI. We compared the incidence of UTI during the six months prior to and the six months following the initiation of prophylactic treatment with FT. a total of 86 patients were enrolled in the study, including 20 men and 66 women, with a median age of 56.5 years [44-70]. Forty-one had underlying urological diseases, and 24 were immunocompromised, including 16 kidney transplant recipients. FT prophylaxis was associated with a dramatic decrease in the incidence of UTI on multivariate analysis, with an incidence rate ratio of 0.15 [0.11-0.20] in women, and 0.05 [0.02-0.16] in men. Adverse events were reported by 12(13.9%) patients, leading to FT discontinuation in 3(3.4%). FT prophylaxis was associated with a 85-95% reduction in the incidence of UTI in patients with recurrent UTI and predisposing conditions.

Vector-borne diseases (VBDs) are an increasing threat to animal and human health worldwide. Due to the complexity of VBD transmission and ecology, informing responses to VBDs can be challenging. A One Health approach provides a powerful framework for addressing these threats, but its effectiveness depends on timely access to and integration of diverse and often fragmented data categories. Here we outline three key community actions: applying global metadata and data standards, depositing data into global repositories and responsible shared data usage, which can enhance VBD data sharing. We highlight how these data-sharing practices allow for the development of new informatic infrastructure, established by the One Health VBD Hub project, to facilitate analyses and ultimately enhance our ability to provide timely responses to endemic and emerging VBD threats.

Multidrug-resistant pathogens cause severe infections with substantial morbidity and mortality in neonates, infants and children, as they do in adults. However, the approval of therapies for multidrug-resistant infections in paediatric patients often lags years behind approval for adults, which creates an untenable situation for people who care for affected children. Many issues contribute to the current unacceptably long period between adult and paediatric new drug approval, including the requirement for sequential age group enrolment in clinical trials, the types of regulatory studies required and a lack of alignment between regulatory authorities. To streamline paediatric drug development, more efficient approaches to investigational and approval processes that meet acceptable safety and efficacy metrics are required. For products that address an urgent unmet need in children, approval should be based primarily on matching drug exposure to levels in adults and on extrapolating safety and efficacy data from adults, where appropriate, rather than on requiring clinical trials in all paediatric age groups for each approved indication in adults. In addition, real-world and post-approval data could be used to support early, limited drug approval for paediatric patients. However, there are economic challenges in developing anti-infective drugs for paediatric populations and increased funding is needed to ensure that neonates, infants and children globally have timely access to safe, effective and life-saving therapies. Les agents pathogènes multirésistants provoquent des infections graves associées à une morbidité et à une mortalité élevées chez les nouveau-nés, les nourrissons et les enfants, tout comme chez les adultes. Cependant, l’autorisation de traitements contre les infections multirésistantes chez les patients pédiatriques accuse souvent un retard de plusieurs années par rapport à celle accordée aux médicaments destinés aux adultes, ce qui crée une situation intenable pour les personnes qui ont à charge les enfants touchés. De nombreux facteurs contribuent au délai actuellement inacceptable entre l’autorisation d’un nouveau médicament chez l’adulte et chez l’enfant, notamment l’obligation de recruter les groupes d’âge de manière séquentielle dans les essais cliniques, les types d’études réglementaires requises et un manque de coordination entre les autorités réglementaires. Afin de rationaliser le développement des médicaments pédiatriques, il est nécessaire de mettre en place des approches plus efficaces pour les processus d’investigation et d’autorisation afin que ceux-ci répondent à des critères acceptables en matière de sécurité et d’efficacité. Pour les produits destinés à répondre à un besoin urgent non satisfait chez l’enfant, l’autorisation devrait reposer principalement sur la mise en correspondance de l’exposition au médicament et des niveaux observés chez l’adulte ainsi que sur l’extrapolation des données de sécurité et d’efficacité issues des études chez l’adulte, le cas échéant, plutôt que sur l’exigence d’essais cliniques dans tous les groupes d’âge pédiatriques pour chaque indication approuvée chez l’adulte. En outre, des données issues de la pratique clinique et post-autorisation pourraient servir à étayer une autorisation précoce et limitée de ces médicaments pour les patients pédiatriques. Toutefois, la mise au point de médicaments anti-infectieux destinés aux populations pédiatriques pose des défis économiques. Dès lors, un financement accru est nécessaire pour garantir que les nouveau-nés, les nourrissons et les enfants du monde entier aient accès en temps opportun à des traitements sûrs, efficaces et vitaux. Los patógenos multirresistentes causan infecciones graves con una morbilidad y mortalidad considerables en neonatos, lactantes y niños, al igual que en las personas adultas. Sin embargo, la aprobación de tratamientos para infecciones multirresistentes en pacientes pediátricos suele producirse años después de su aprobación para adultos, lo que genera una situación insostenible para quienes atienden a los niños afectados. Numerosos factores contribuyen al periodo, actualmente inaceptablemente largo, que transcurre entre la aprobación de nuevos medicamentos para adultos y para pacientes pediátricos, entre ellos la exigencia de una inclusión secuencial por grupos de edad en los ensayos clínicos, los tipos de estudios regulatorios requeridos y la falta de armonización entre las autoridades reguladoras. Para agilizar el desarrollo de medicamentos pediátricos, se requieren enfoques más eficientes para los procesos de investigación y aprobación que cumplan criterios aceptables de seguridad y eficacia. En el caso de productos destinados a cubrir una necesidad urgente no satisfecha en la población infantil, la aprobación debería basarse principalmente en alcanzar niveles de exposición al medicamento comparables a los observados en adultos y en extrapolar, cuando proceda, los datos de seguridad y eficacia obtenidos en adultos, en lugar de exigir ensayos clínicos en todos los grupos de edad pediátrica para cada indicación aprobada en adultos. Además, los datos procedentes de la práctica clínica real y los obtenidos tras la aprobación podrían utilizarse para respaldar una aprobación temprana y limitada de medicamentos para pacientes pediátricos. No obstante, existen desafíos económicos para el desarrollo de medicamentos antiinfecciosos destinados a la población pediátrica, y se necesita una mayor financiación para asegurar que los neonatos, lactantes y niños de todo el mundo tengan acceso oportuno a tratamientos seguros, eficaces y que salvan vidas. إن مسببات الأمراض المقاومة للعقاقير المتعددة تؤدي إلى حالات عدوى خطيرة ذات معدلات عالية من الإصابة بالأمراض والوفيات لدى حديثي الولادة، والرضع، والأطفال، كما هو الحال لدى البالغين. ومع ذلك، فإن الموافقة على علاجات العدوى المقاومة للعقاقير المتعددة لدى الأطفال، غالبًا ما تتأخر لسنوات عن الموافقة عليها لدى البالغين، مما يخلق وضعًا صعبًا للغاية بالنسبة للأشخاص الذين يرعون الأطفال المصابين. تسهم العديد من العوامل في طول الفترة الحالية غير المقبولة بين الموافقة على الأدوية الجديدة للبالغين والأطفال، بما في ذلك اشتراط التسجيل المتسلسل للفئات العمرية في التجارب الإكلينيكية، وأنواع الدراسات التنظيمية المطلوبة، وعدم التنسيق بين الهيئات التنظيمية. وحتى تتسم عملية تطوير الأدوية للأطفال بالسلاسة، يجب اتباع أساليب أكثر فعالية في عمليات الاستقصاء والموافقة، بما يضمن الوفاء بمعايير السلامة والفعالية المقبولة. بالنسبة للمنتجات التي تلبي حاجة ملحة غير مستوفاة لدى الأطفال، يجب أن تستند الموافقة في المقام الأول إلى مطابقة مستويات التعرض للعقار مع مستويات البالغين، واستقراء بيانات السلامة والفعالية من البالغين، عند الحاجة، بدلاً من اشتراط إجراء تجارب إكلينيكية على جميع الفئات العمرية للأطفال لكل استخدام مُعتمد لدى البالغين. إضافةً إلى ذلك، يمكن استخدام بيانات الواقع العملي وبيانات ما بعد الموافقة لدعم الموافقة المبكرة والمحدودة للأدوية لمرضى الأطفال. مع ذلك، توجد تحديات اقتصادية في تطوير العقاقير المضادة للعدوى للسكان من الأطفال، وهناك حاجة إلى زيادة التمويل لضمان حصول حديثي الولادة، والرضع، والأطفال في جميع أنحاء العالم على علاجات آمنة وفعالة ومنقذة للحياة في الوقت المناسب. 多重耐药病原体不仅会在新生儿、婴儿和儿童中，也会在成人中导致严重感染，且致病率和致死率都相当高。然而，针对儿科患者的抗多重耐药菌感染疗法的审批往往比成人疗法滞后多年，从而让需要照护此类患儿的人员陷入难以维持的局面。导致当前成人和儿科用新药审批时间之间存在无法接受的差距的原因有很多，包括临床试验需按年龄组依次入组、监管机构对研究类型有特定要求以及监管当局之间缺乏协调统一。如要简化儿科药物研发流程，需要采取更有效的方法来优化试验和审批流程，并达到可接受的安全和疗效指标。审批可解决儿童紧急未满足需求的产品时，若适当，应主要基于药物暴露水平是否与成人相匹配，并根据成人数据外推安全性和疗效，而非要求逐一针对已获批的成人适应症，在各年龄组儿科患者之间开展临床试验。此外，真实世界数据和审批后数据可用于支持提早、有限制地审批儿科患者用药。但是，为儿科患者群体研发抗感染药物还会面临多重经济挑战，需加大资金投入以确保全球新生儿、婴儿和儿童能够及时接受可挽救其生命的安全有效疗法。. Патогены, обладающие множественной лекарственной резистентностью, вызывают тяжелые инфекции со значительными показателями заболеваемости и смертности среди новорожденных, младенцев и детей старшего возраста, в равной степени как и среди взрослых. Однако одобрение схем лечения инфекций со множественной лекарственной резистентностью для пациентов детского возраста отстает на годы от решения этого же вопроса для взрослых, что создает неприемлемую ситуацию для лиц, осуществляющих уход за больными детьми. Причин такого недопустимо длительного периода между одобрением новых препаратов для применения у взрослых и детей множество, в том числе это требование привлечения последовательных возрастных групп к участию в клинических исследованиях, требуемые типы регуляторных исследований, а также недостаточная согласованность работы регулирующих органов. Чтобы упростить разработку лекарств для детей, необходимы более эффективные подходы к процессам исследований и одобрения, которые отвечают приемлемым показателям безопасности и эффективности. Для продукции, отвечающей острой неудовлетворенной потребности в медицинской помощи детям, процедура одобрения должна опираться главным образом на сопоставление воздействия препарата с уровнями, достигаемыми у взрослых пациентов, и на экстраполяцию данных по безопасности и эффективности, собранных для взрослых, когда это уместно, а не на требование обязательного проведения клинических испытаний во всех возрастных группах пациентов-детей для каждого показания к применению, одобренного для взрослых. Кроме того, данные реальной клинической практики и пострегистрационного применения можно использовать для обоснования раннего ограниченного одобрения тех или иных препаратов в случае применения у пациентов детского возраста. Однако разработка противоинфекционных препаратов для педиатрических популяций сталкивается с проблемами экономического характера, и необходимо увеличение финансирования для того, чтобы новорожденные, младенцы и дети старшего возраста во всем мире гарантированно имели своевременный доступ к безопасному и эффективному лечению, спасающему жизни.

Rapid point-of-care tests (POCTs) are increasingly used to support clinical decision making and appropriate antibiotic prescribing. Whilst a few studies have explored healthcare workers' views on using POCTs in paediatric febrile illness, little is known about the perspectives of children and young people (CYP) who may undergo these tests. This study aimed to explore CYP acceptability and perceptions of POCTs. Three focus groups were conducted with CYP aged 12-18 years, from Young Persons' Advisory Groups, at university hospitals in Newcastle and London, UK. Data were collected using questionnaires and semi-structured group discussions. Qualitative thematic analysis was undertaken to identify key themes relating to POCT acceptability, availability and perceived impact. A total of 54 CYP participated (10 in 2017, 25 in 2018, and 19 in 2025). The majority supported the implementation of POCT tests, provided they are accessible through community or hospital healthcare services. Key themes included altruism, test reliability, and the need for healthcare advice or review in-person following the test. CYP prefer non-invasive tests such as saliva-based sampling, over blood tests, and reported aversion to urine samples. POCTs were viewed as a means of improving assessment of unwell children and potentially reducing the burden on healthcare services if results were reassuring. CYP are in favour of using POCTs to facilitate and improve the care they receive. They recognised the potential benefits they might have, but highlighted important limitations particularly regarding availability, interpretation and potential impact on the wider healthcare system.

UK is one of a few countries that are likely to meet WHO HCV elimination targets of reducing incidence to <2 per 100 person years in People Who Inject Drugs (PWID), but the economic case may be important for investment elsewhere and in future in UK. We illustrate the impact of real-world scaled-up HCV treatment to assess under what drug treatment costs could the investment be cost-saving. We utilised a mathematical and economic model, calibrated to public health surveillance data and HCV testing and treatment scale-up from 4 regions in UK, that projects trends in HCV prevalence and incidence among PWID from 2016 to 2030, and deaths and incremental cost-effectiveness ratio (ICER) from 2016 until 2065, compared to counterfactual of no community and prison testing and treatment scale-up. We vary HCV drug price from &#xa3;1000 to &#xa3;10,000 per person treated and estimate the % of runs that are cost-saving for each price. Scaling up HCV treatment in PWID is estimated to avert on average 35-60% of HCV infections over 2016-2030 in the four regions compared to a counterfactual of no treatment scale-up. Over 50 years the intervention would prevent 13 to 34% of deaths assuming current HCV treatment rates continue. The ICER is cost-saving from <&#xa3;1000 to &#xa3;5000 across the four regions with the average (weighted by estimated number of PWID in each region) of these threshold costs at approximately &#xa3;3000 per course. The majority of costs from HCV (&#x223c; 78% before treatment scale-up) and contribution to reducing burden is due to severe liver disease (cirrhosis and decompensated cirrhosis). Scaling up HCV testing and treatment to meet WHO elimination targets is highly cost-effective and could be cost-saving at realistic discounted drug costs. The economic case for HCV elimination can be made for countries that are not yet on track.

Older adults (people aged >60&#xa0;years) are often stereotyped as being asexual, reflecting a broader lack of research into the sexual lives of this age group. Few studies have examined sexual well-being among older adults in low- and middle-income countries, especially in Africa. This scoping review aims to identify and synthesize the factors that affect sexual functioning and quality of sexual life among older adults in Africa. Following the approach of Arksey and O'Malley, a scoping review was conducted on determinants affecting the quality of sexual life among older adults in Africa. Seven databases were searched: PubMed, Google Scholar, CINAHL, Scopus, Web of Science, ProQuest and AJOL. Full texts were reviewed to determine the final set of papers for inclusion. Included papers were published, with publication dates between January 2010 and January 2025. Data were extracted on the study population, study design, mean age of the study participants, aims of the study and the determinants affecting the quality of sexual life, and summarized using narrative synthesis. A total of 14,398 citations were identified in the database search, and seven studies were included in the review. The age of study participants averaged approximately 70&#xa0;years. The research consisted of three qualitative and four quantitative articles. Four studies were conducted in Nigeria, and one each from South Africa, Morocco and Tanzania. Our review identified four categories of determinants influencing the quality of sexual life among older adults in Africa: psychological, sociocultural, physiological and health. Psychological determinants, including past trauma, performance anxiety and societal expectations, were identified across five studies. Sociocultural determinants, including sexual attitudes and culturally embedded behaviors, were examined in six studies, and found to shape the sexual functioning and behaviors of older adults. Physiological determinants, such as menopause and erectile dysfunction, were reported in four studies and associated with reduced sexual activity. Health determinants, including chronic conditions and pharmacological factors (medications), were identified in five studies as influencing older adults' sexual function and intimacy. Multiple, complex determinants affect the quality of sexual life among older adults in Africa. Our study findings have implications for designing sexual health services among older adults in Africa.

We aimed to systematically review studies that had developed, used, or assessed the psychometric properties of vision or hearing bolt-ons for EuroQol 5-Dimension 3-Level instrument (EQ-5D-3L) and EuroQol 5-Dimension 5-Level instrument (EQ-5D-5L). A systematic review was conducted up to 17 March 2025, in Embase, PubMed, and Web of Science following the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guideline. Findings for EQ-5D-3L and EQ-5D-5L with vision and hearing bolt-ons, including the number of different bolt-on wordings and psychometric performance, were summarized narratively. The review included 21 and eight publications for vision and hearing bolt-ons, respectively. More differentiated bolt-ons were developed for the EQ-5D-5L than for the EQ-5D-3L (vision: 9 vs 1; hearing: 20 vs 1). Among them, 4 vision and 13 hearing bolt-ons for EQ-5D-5L originated from 2 separate qualitative development studies. Six studies (vision: 3; hearing: 3) used qualitative research during item development. Across general-population and patient-population studies, both vision and hearing bolt-ons reduced the ceiling effects (vision: 4.3%-38.1%; hearing: 1.65%-18.8%) and showed good convergent validity with relevant external measures (eg, HUI-3, Cat-PROM5). However, convergent validity was weaker for some clinical measures, including visual acuity and hearing thresholds. Known-group validity based on relevant clinical characteristics (eg, visual acuity, unilateral vs bilateral hearing loss) was reported. Responsiveness, test-retest reliability and patient-proxy agreement evidence was limited. Although psychometric properties were generally favorable, the evidence base remains partial and heterogeneous. This review informs future development of bolt-ons that should prioritize identifying the most appropriate item wordings and exploring psychometric properties using both qualitative and quantitative approaches in relevant patient populations.

Appropriately designed, conducted, and reported randomised controlled trials (RCTs) in children and adolescents inform treatment and health-care decisions made by young people, families, researchers, clinicians, regulators, funders, policy makers, and other interest holders. To critically evaluate, interpret, and apply trial results, readers require access to a complete and transparent report of what was planned, done, and found, taking unique considerations specific to children and adolescents into account. Harmonised guidance based on evidence and consensus is needed to optimise standardised reporting and reduce research waste in paediatric RCTs. As an extension to the Consolidated Standards of Reporting Trials (CONSORT) 2025 statement, the CONSORT-Children and Adolescents (CONSORT-C) 2026 reporting guideline aims to improve the quality and completeness of reporting of paediatric RCTs that involve participants aged 0-19 years. The Enhancing the Quality of Transparency of Health Research (EQUATOR) Network's published framework primarily informed the development of CONSORT-C 2026. A literature review was conducted to generate a list of candidate reporting items. To obtain direct input from young people and family caregivers throughout the project, a Youth Advisory Group and a Family Caregiver Advisory Group were formed. An international Delphi study with a priori consensus thresholds, consensus meeting, group writing of the explanation and elaboration paper, and pilot testing were conducted. CONSORT-C 2026 consists of a checklist with 13 new reporting items, including one youth-generated and six youth-endorsed items; the accompanying explanation and elaboration paper explains all items and offers examples of good reporting. CONSORT-C 2026 can be considered a minimum set of reporting items applicable to paediatric RCT reports reflecting the priorities of clinicians, researchers, young people, family caregivers, and other interest holders. Widespread implementation and uptake of CONSORT-C 2026 should optimise the usability of trial results for these populations, improve the reproducibility of trial results, and reduce research waste.

Rubella immunity plays a key role in preventing congenital rubella syndrome, but longitudinal data on antibody stability remain limited. To evaluate rubella IgG seroprevalence, seroconversion, and changes in rubella IgG concentrations over time. We conducted a retrospective cohort study of 2,022 consecutive individuals from Region Zealand, Denmark, each with at least two serum samples submitted for routine rubella IgG testing between 11 September 2018 and 30 May 2025. Pairedsamples from each individual were analysed. At baseline, 88.6% of participants were seropositive, increasing to 90.6% at follow-up. The cohort was predominantly female (99.4%) and mean age at first sample was 29.8&#x2009;years. Among initially seronegative individuals, 75 seroconverted, while 34 individuals initially seropositive seroreverted. Median IgG levels among seroconverts were 23.5&#x2009;IU/mL (range 10-350&#x2009;IU/mL). Individuals who remained seropositive showed a modest yet statistically significant median decrease of 8.4% between the first and second samples (Hodges-Lehmann ratio = 0.92, 95% CI: 0.91-0.93, p&#x2009;<&#x2009;0.0001), with minimal association between antibody change and time interval (Spearman's &#x3c1; = -0.058, p&#x2009;=&#x2009;0.015). In this cohort of routinely tested individuals, rubella IgG levels remained broadly stable, indicating sustained rubella seropositivity over time. Seroconversion and seroreversion occurred in a small subset of individuals, supporting the continued monitoring of rubella immunity, particularly among women of reproductive age. Maintaining high vaccination coverage remains important to sustain rubella elimination and prevent congenital rubella syndrome.