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Data science methods can provide novel and pragmatic approaches for preventing and controlling non-communicable diseases (NCDs) in Africa. This study highlights current efforts, opportunities, and challenges in leveraging data science methods to accelerate and advance the prevention and control of NCDs in Africa. We undertake a systematic review and gap analysis, as registered in PROSPERO (CRD42023406237). Our findings suggest several data science methods have been used in research across the four leading NCDs in Africa. However, limited information exists on their application to improve disease surveillance, risk factor identification and characterization, prevention, treatment, drug discovery and rehabilitation. Machine learning outperforms traditional statistical methods in improving risk stratification in most studies (80.8%) designed for the prevention and control of NCDs. Notwithstanding, most (76.0%) data science techniques for NCDs prevention and control remain in the exploratory research phase, with limited clinical or public health application and minimal impact on the African population. There are critical gaps along the continuum of data generation, data quality, method development, and validation, which may be attributed to inadequate funding, capacity development, policy shortcomings, and infrastructure deficits. Considerable gaps exist in intra-African collaboration, data sharing, and replication, which hinder the cross-cultural replication and applicability of data science methods for NCDs prevention and control in Africa. Multi-sectoral interventions that promote interdisciplinary capacity building, investment, and knowledge linkages, taking into account indigenous epistemologies, are needed to harness the enormous potential of data science to accelerate the prevention and control of NCDs in Africa. Data science offers innovative and practical approaches for accelerating the prevention and control of non-communicable diseases (NCDs). However, there are significant limitations that hinder their use for improving health outcomes in Africa. We highlight current efforts, opportunities, and challenges in leveraging data science to accelerate the prevention and control of NCDs in Africa. Most data science applications for NCD prevention and control in Africa remain in the exploratory phase, thereby limiting real-world clinical or public health utility. Multi-sectoral interventions that promote interdisciplinary capacity building, investment, and the linking of datasets are needed to harness the enormous potential of data science to accelerate the prevention and control of NCDs in Africa.
Generative artificial intelligence (GenAI) and large language models are rapidly entering mental health research and service delivery, yet their dominant use remains symptom-centric, emphasizing screening, classification, triage, and risk detection. For older adults, mental health is often inseparable from existential concerns: loss of social role, disrupted continuity of self, loneliness, diminished dignity, and questions of legacy. This perspective argues that GenAI should not be conceptualized as an autonomous substitute for clinicians, nurses, social workers, or family caregivers. Instead, it may be better understood as an interactional infrastructure for meaning-centered care in later life. Drawing on meaning-centered psychotherapy, dignity therapy, life review, gerotranscendence theory, care ethics, and implementation science, we propose a Sensing-Narrating-Connecting-Governing framework. In this model, multimodal AI systems help detect existential and relational cues, support life-review conversations, co-construct dignity-preserving narratives, connect older adults with human care networks, and operate under explicit safeguards for privacy, hallucination, dependency, crisis escalation, and cultural adaptation. The proposed framework shifts evaluation from model performance alone toward existential well-being, dignity, continuity of self, therapeutic alliance, equity, and workflow integration. We conclude that GenAI may contribute to public mental health only when deployed as a bounded, human-supervised, culturally responsive layer of relational augmentation rather than as a replacement for human presence.
Rural and remote communities remain hard-to-reach populations, with persistent barriers to accessing timely, appropriate, and culturally relevant mental health care. Within these settings, farmers face a wide range of unique work-related stressors that can contribute to mental health challenges. Research shows that farmers experience higher levels of depression, anxiety, and suicide compared to the general population, yet have low rates of seeking mental health support. Low rates of help-seeking among farmers have been linked to mental health stigma, cultural norms of stoicism and independence, and skepticism toward non-farming professionals. As awareness about farmers' urgent mental health needs grows, there is increasing pressure on policymakers, industry groups, and healthcare organizations to provide support. However, without culturally responsive approaches that reflect the realities of farming, these efforts risk falling short. Mental healthcare professionals (MHCPs) who already work with farmer clients are well positioned to inform the development and implementation of policies, practice, and training aimed at addressing farmer mental health issues. Therefore, the purpose of our study was to address this gap by exploring the experiences of MHCPs who work with farmers to identify the strategies they use to effectively engage and build trust in a therapeutic setting. Using descriptive phenomenology, we conducted individual semi-structured interviews between March and May 2024 with 25 MHCPs practicing in Alberta or Ontario, Canada. All participants lived in a rural area, had been practicing for at least 12 months, and provided counselling services to farmers. Interviews were conducted virtually through Zoom or by telephone. Interviews were recorded and transcribed verbatim. Data were analyzed using thematic analysis. Our analysis revealed five themes that were deemed important for effectively engaging and building trust with farmer clients: understanding the unique stressors of farmers, setting the tone, building trust, providing psychoeducation, and tailoring therapy and sustaining connections. We translated these themes to create a conceptual model, called the Farmer-Centered Therapy Framework, which provides a visual summary of the stepwise approach MHCPs use working with farmer clients to achieve therapeutic alliance. Effectively engaging farmers and building trust in therapeutic settings is a multifaceted process that begins with understanding the distinct culture, values, stressors, and lifestyle of farm life. This study addresses a critical and timely gap in the literature by exploring the experiences of MHCPs who work directly with farmers on their mental health issues. The findings have important implications for rural and remote health policy and practice by highlighting the need for culturally informed mental health services that align with the values and lived experiences of farmers. Presenting our findings through the Farmer-Centered Therapy Framework can guide culturally responsive approaches for supporting MHCPs who have farmer clients. Furthermore, integrating this knowledge into provider training and service delivery models can reduce real and perceived barriers to services, increase engagement, and improve the mental health outcomes in farming communities.
The integration of Artificial Intelligence (AI) into modern medicine has revolutionised diagnostic accuracy, yet it generates a critical ethical dilemma: as healthcare becomes more data-driven, it risks eroding the high-touch essence of care. As algorithms increasingly shape clinical decision-making, patients risk being reduced to data points rather than persons with unique life stories. This paper examines the tension between AI's calculative logic and the narrative nature of illness, introducing the Processing-Witnessing Model. This framework distinguishes between algorithmic processing (speed, optimisation) and human witnessing (presence, interpretation, and narrative understanding). While AI excels at managing disease as biological dysfunction, it cannot address illness as the lived experience of suffering. This paper argues that the opacity of black-box systems creates a contextual void, enabling a form of epistemic violence that renders the patient's story invisible. Furthermore, the normalization of the screen gaze threatens the therapeutic alliance. Ironically, studies rating AI chatbots as 'more empathetic' are interpreted here not as evidence of machine moral agency, but as a symptom of systemic burnout. This makes narrative ethics a priority for medical education. The physician's role should evolve from data supervisor to cultural mediator, ensuring that while machines process the biological hardware, clinicians provide the interpretive software of meaning.
While randomised controlled trials have demonstrated the efficacy of ustekinumab for treating Crohn's disease (CD), real-world effectiveness and patient experience in heterogeneous clinical populations remain less well characterised. We aimed to assess the effectiveness and safety of ustekinumab in routine clinical care incorporating patient-reported outcomes. This prospective multicentre study recruited adult patients initiating ustekinumab for CD as part of routine clinical care across 22 UK hospitals. Study visits were conducted at baseline and at Weeks 8, 16/20, 56, 80 and 104. Data collected included participant demographics, disease phenotype, previous treatment history, disease activity scores, laboratory measures, dosing regimens, patient-reported outcomes (patient experience, quality of life [QoL] and treatment satisfaction) and adverse events. The primary outcome was corticosteroid-free clinical remission (defined as mHBI < 5) at Week 56. Six hundred one participants were recruited between October 2019 and August 2023, with 20% naïve to advanced therapies. At baseline, 43% of participants were assessed as being in clinical remission according to mHBI, whereas only 12% had quiescent disease per the IBD-Control questionnaire. The primary endpoint was achieved by 33% of participants (95% CI, 30%-37%). Cumulative probabilities of ustekinumab persistence were 78% at 1 year and 63% at 2 years. The IBD-Control-8 score showed improvement from baseline to Week 8, increasing from a median of 5 (IQR: 2-10) to 12 (IQR: 8-14), though QoL impairment remained evident in many participants. Most adverse events were mild and consistent with the established safety profile of ustekinumab. In this large real-world cohort, ustekinumab treatment was associated with sustained improvements in both clinical outcomes and QoL measures. Our data suggest that patients treated in clinical practice differ markedly from Phase 3 trial participants. QoL, and not only disease activity as assessed using a conventional disease activity score, may play a significant role in the decision to initiate ustekinumab. Systematic integration of QoL measures into routine care may improve patient care and treatment outcomes.
To report updated patient-reported (PRO) health-related quality of life (HRQOL) findings and evaluate the effect of disease progression on HRQOL using data from the final analysis of the PRIMA/ENGOT-OV26/GOG-3012 trial. Patients were randomized 2:1 to niraparib first-line maintenance or placebo. Longitudinal HRQOL was a prespecified secondary endpoint assessed via European Organisation for Research and Treatment of Cancer QOL-Core Questionnaire (EORTC QLQ-C30) and -Ovarian Cancer module (EORTC QLQ-OV28), Functional Assessment of Cancer Therapy Ovarian Cancer Symptom Index (FOSI), and EuroQol 5-dimension 5-level questionnaire with visual analog scale (EQ-VAS). Post hoc analyses evaluated least-squares mean change from baseline or last on-treatment visit before disease progression (clinical cutoff: April 8, 2024). Questionnaire completion rates exceeded 89% through cycle 24 and were 80% at end of treatment. Early differences in gastrointestinal symptom scores between arms resolved over time, and no differences in overall HRQOL were observed. Disease progression reduced overall HRQOL across arms, with marked reductions in EORTC QLQ-C30 overall HRQOL, FOSI, and EQ-VAS scores that never recovered to pre-progression levels. Progression also resulted in sustained deterioration across all EORTC QLQ-C30 and QLQ-OV28 functional scales and worsening symptom scores, particularly for fatigue, dyspnea, pain, and appetite loss. Similar results were observed when patients were evaluated by homologous recombination deficiency status. In the final PRIMA PRO analysis, results confirmed that niraparib first-line maintenance did not negatively affect HRQOL versus placebo. Disease progression caused sustained HRQOL deterioration across arms, emphasizing the clinical importance of extending progression-free survival to preserve patient HRQOL. NCT02655016.
Life participation (LP) has been identified as a critically important core outcome for trials in people receiving dialysis. We aimed to validate the Standardized Outcomes in Nephrology-LP (SONG-LP) instrument in people receiving dialysis. A psychometric evaluation of the SONG-LP instrument in adults receiving dialysis (including hemodialysis [HD] and peritoneal dialysis [PD]) was completed through a multinational online survey. Internal consistency, test-retest reliability, convergent validity, discriminant validity, and known group comparisons (for dialysis modality and dialysis duration) were assessed. In total, 250 adults receiving dialysis (69 PD, 47 home HD, and 134 in-center HD) from 13 countries completed surveys at baseline, and 204 participants (82%) completed the survey 1 week later. The SONG-LP instrument demonstrated strong internal consistency (Cronbach's α = 0.89, 95% confidence interval [CI]: 0.87-0.91, baseline) and test-retest reliability over 1 week (intraclass correlation coefficient [ICC] of 0.76, 95% CI: 0.70-0.81). There was a high correlation (0.76, 95% CI: 0.69-0.81) with the Patient-Reported Outcomes Measurement Information System (PROMIS) Ability to Participate in Social Roles and Activities (APS) Short Form 8a. There was moderate to high correlation with measures assessing concepts related to LP measured by the EuroQol-5 Dimension (EQ-5D) (0.62, 95% CI: 0.53 - 0.69) and PROMIS Cognitive Functional Abilities Subset Short Form 4a (0.49, 95% CI: 0.38 - 0.57). The SONG-LP instrument is an internally consistent and reliable measure of LP for people receiving dialysis. This study provides preliminary evidence supporting its psychometric validity, offering a foundation for further evaluation of its use in clinical trials.
Depressive symptoms are common among older adults and can significantly impact their quality of life. However, many older adults face barriers to accessing psychological treatment. Internet-based cognitive behavioral therapy (iCBT) is a promising alternative to face-to-face treatments, but its feasibility among older adults has been less extensively studied than in adult populations. This study evaluated the feasibility of guided iCBT for adults aged 55 years and older with mild to moderate depressive symptoms recruited from the general population. This study is a feasibility study with a single-group, pretest-posttest design (n=21), in which all participants received guided iCBT for 8 weeks. Assessments were conducted at baseline (T0) and after the intervention (T1). The primary outcome was feasibility, conceptualized as satisfaction, usability, engagement, and uptake of iCBT. Secondary outcome measures included depression severity, working alliance, and technical alliance. Participants were mostly highly educated (13/21, 61.9%), female (18/21, 85.7%), had an average age of 59.85 (SD 4.19; range 55-68) years, and reported moderate digital literacy. Feasibility outcomes indicated high satisfaction and engagement and moderate usability. Working alliance was rated as good by both participants and coaches, and technical alliance was rated as moderate by the participants. There was a nonsignificant modest decrease in depressive symptoms (Cohen d=0.47). Of the 20 participants who started the intervention, all completed the first 2 modules, but completion declined across the remaining 6 modules, with only 1 (5%) participant completing all modules. This study found that guided iCBT has the potential to be a feasible option for older adults experiencing depressive symptoms, with participants reporting generally positive satisfaction, moderate engagement, and a moderate therapeutic bond with their coaches. However, below-average usability ratings and a moderate technical alliance suggest that some aspects of the platform require improvement. Future research should focus on improving usability and adherence, as well as testing the intervention in a larger and more diverse population.
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.
Fragmented interfaces between municipal and specialist services make integrated mental healthcare difficult, and coordination in rural settings presents unique challenges. Flexible Assertive Community Treatment (FACT) aims to reduce fragmentation through multidisciplinary, community-based care. However, evidence remains limited regarding the services rural FACT teams deliver and how integrated care is enacted in everyday practice. This study examined service distribution and the coordination practices that enable integration in a rural Norwegian FACT team. We used an explanatory sequential mixed-methods design. A prospective service mapping captured 2,319 patient-related contacts among 70 patients over 12 weeks and was analysed with time-weighted descriptive statistics. A subsequent focus group with team members was analysed using reflexive thematic analysis. Integration occurred by building (quantitative results informed the interview guide) and merging (interpretive integration of quantitative patterns and qualitative themes). Approximately 80% of services were delivered directly by the team and 20% in collaboration with external partners. Service delivery was broadly divided between clinical contacts (one-third) and interprofessional coordination/collaboration (one-third); the remaining third comprised daily life mastery, therapeutic alliance, and social support. 28% of contacts were conducted via phone, text, or videoconference, mainly for rapid coordination. Qualitative findings identified three interrelated practices underpinning integration under rural constraints: collaborative alliance, involving trust-based partnerships with patients, families, and services; information alignment, encompassing the gathering, refinement, and communication of fragmented information to establish a shared and actionable understanding; and safety valve thinking, referring to anticipating uncertainty and maintaining contingency plans to flexibly organise care within the rural network of care. Integrated care in rural FACT practice is enabled through extensive coordination and collaborative work, supported by relational and adaptive practices. These findings underscore the importance of context-sensitive adaptations alongside model fidelity to sustain patient safety and continuity of care.
Phenolic acid decarboxylases (PADs) convert bio-based hydroxycinnamic acids into valuable hydroxystyrene monomers under mild reaction conditions. These compounds are in high demand in polymer production, cosmetics, and flavoring. Especially 4-vinyl syringol, the decarboxylation product from sinapic acid, generates polymers with similar thermal stability and higher glass transition temperatures than vinyl guaiacol, the decarboxylation product from ferulic acid. However, natural PAD enzymes typically show slow turnover with sinapic acid. In addition, establishing a viable industrial process requires enzymes operating under elevated temperatures. To tackle these issues, we assessed five thermostable ancestral PADs towards their activity and stability for the conversion of ferulic acid and sinapic acid at different temperatures. A combinatorial active site library was prepared for the most thermostable ancestor. We expanded the substrate scope of a selected PAD ancestor to include sinapic acid through directed mutagenesis. A trade-off between ferulic-/caffeic acid and sinapic acid was observed and investigated via molecular dynamics simulations. The most stable ancestor was identified with a half-life of 3.65 days, analyzed at 50°C. We found the Ile29Ser-Leu80Ser-Ile93Ala triple mutation (SSA) to effectively expand the substrate scope with an 11-fold increase in catalytic efficiency for sinapic acid, and a half-life of 1.12 days at 50°C, being approximately 1.6-fold higher than the frequently used PAD from Bacillus subtilis.
Our objective was to determine the extent to which clinical outcomes at 3 months predict the 6- to 12-month trajectory in people presenting with mild or moderate traumatic brain injury (TBI). We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, EMBASE, EBSCO, and the Web of Science Citation Index from 2005 until May 2025. All observational or interventional study designs that reported clinical outcomes in patients at 3 months, and at a later time point, following mild or moderate TBI were eligible for inclusion. Two authors independently selected and extracted data. Risk of bias was assessed using the Downs and Black checklist. Thirty studies (29 observational, 1 interventional) involving 7993 patients (7781 with mild TBI [mTBI]) met the inclusion criteria. Study quality was variable, and heterogeneity in study inclusion criteria and outcome reporting precluded meta-analyses and identification of patient and injury predictors of post 3-month outcome trajectory. Vulnerable populations-including older adults, those with pre-existing cognitive impairment, psychiatric illness, or intoxication-were frequently excluded. Analysis of the four most commonly reported outcome measures (Rivermead Post-Concussion Symptoms Questionnaire, Extended Glasgow Outcome Scale, Short Form 36 Health Survey, and Quality of Life after Brain Injury)-revealed symptom and functional improvement over time, particularly from hospital discharge to 3 months post-injury. However, substantial problems persist thereafter with 21-65% of patients continuing to experience symptoms or impairment, depending on cohort and outcome measure. The small number of patients with moderate TBI precluded comparison of outcomes to patients with mTBI. To improve clinical care, research, and patient experience, future targeted studies should identify factors determining the post-TBI outcome trajectory.
To describe inequalities in health indicators relevant for quality of care to people with rheumatic and musculoskeletal diseases (RMDs) across Europe by comparing RMD health system indicators across European Alliance of Associations for Rheumatology (EULAR) member countries. RheumaFacts is an EULAR initiative to improve the quality of care across Europe by monitoring access to and outcomes of care for people living with RMDs. In this study, we present the first edition of this longitudinal mixed-sources study initiated in 2024. A standardised form including indicators on RMD health resources and organisation, national workforce, and access to care was sent to the 40 National Scientific Rheumatology Societies who were EULAR members in 2024 was sent to the EULAR-member National Scientific Rheumatology Societies of 40 countries. Complementary data on the demographic and economic status of the various countries were extracted from open-source databases such as the WHO and World Bank datasets. Analyses were descriptive. Standardised report forms were returned by 36 of 40 countries (90%). The density of rheumatologists ranged from 0.8 to 6.6 per 100,000 inhabitants (median, 2.9; IQR, 2.1-3.5) across the different countries. The reimbursement of nonpharmacological care on a chronic basis was limited: physiotherapy was reimbursed in 26 of 36 countries (72%), whereas psychological support was reimbursed in only 14 of 36 countries (39%). In 94% of the countries, all conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were available. Despite all countries indicating the availability of at least 1 biologic DMARD, only 12 countries (34%) had access to all biologic DMARDs, and only 18 of 35 (51%) had access to all targeted synthetic DMARDs. Wide cross-national inequalities exist in workforce capacity and reimbursed care for people with RMDs. RheumaFacts delivers the first harmonised basis for monitoring these gaps, enabling EULAR and national societies to track progress and inform health policy makers to advocate for improving the quality of life of people with RMDs.
Chronic spontaneous urticaria (CSU), characterized by recurring itchy wheals (hives) and/or angioedema lasting > 6 weeks without identifiable triggers, affects 1.29% of China's population. China ranks second globally in urticaria disability-adjusted life years (DALYs), thus understanding real-world outcomes is important. We hypothesized that, despite ongoing treatment, a substantial proportion of Chinese patients with CSU experience inadequate disease control and impaired quality of life (QoL), with gaps between their treatment expectations and perceived achievability of optimal control. This study assessed patient-reported burden, treatment patterns, and unmet needs in these patients. This was a cross-sectional study using 40-min online surveys. Patients were recruited through online panels. Eligibility included adults ≥ 18 years with physician-confirmed CSU diagnosis, actively treated. Descriptive analysis was stratified by disease control and treatment type. A total of 400 patients with CSU (mean age 35.09, [SD 7.24] years; 45% female) participated; 2% reported symptom onset < 1 year pre-study, 71% between 1 and 5 years, and 27% > 5 years (mean disease duration 5.31 [SD 4.89]). On the basis of the Urticaria Control Test (UCT), 35% of participants had inadequately controlled disease (UCT < 12), whereas Patient Global Impression of Severity (PGI-S) self-assessment suggested better perceived control (92% mild/no symptoms). Most diagnoses were made by dermatologists (94%); 57% of patients reported no fixed follow‑up schedule. Among inadequately controlled patients, 90% reported sleep disturbance during exacerbations. Most patients (82%) used second-generation antihistamines; one-third used Traditional Chinese Medicine. Complete symptom control was the top treatment goal (mean importance: 8.5/10), yet only 16% believed it achievable (9% of inadequately controlled). One-third of treated patients with CSU reported inadequate disease control impacting QoL. The disconnect between high priority for complete control and low perceived achievability, alongside irregular follow-ups, highlights limitations in current therapies and care delivery. These findings underscore the need for more effective treatments and structured, patient-centered management pathways to optimize CSU care in China.
Timothy syndrome is a multisystemic genetic disorder, classically characterised by prolonged QT interval and subsequent cardiac arrhythmias, neurodevelopmental disorders including developmental delay and autism and syndactyly or hip dysplasia. It is caused by variants in the CACNA1C gene, which encodes the widely expressed Cav1.2 voltage-gated calcium channel. Since its characterisation in 2004, the number of variants in CACNA1C associated with Timothy syndrome has expanded. With advances in sequencing and the inclusion of CACNA1C in genomic screening, further variants have been identified presenting with incomplete features of Timothy syndrome or further aligned phenotypes, which are inconsistent with the original description. In the absence of a formal nomenclature, these presentations have been reported in a proliferation of ill-defined terms, e.g. Atypical Timothy Syndrome. At the same time, advances in knowledge and therapeutics have improved morbidity and life expectancy for these individuals when appropriately identified and managed. Here, we present guidelines for the diagnosis of individuals presenting with variants in CACNA1C, developed by an international panel of experts through Delphi consensus with the involvement of the CACNA1C community. We formalise the language around syndromic presentations linked to CACNA1C variants, reassert and demarcate the classical Timothy syndrome phenotype and provide a structured co-produced definition for CACNA1C-Related Disorder. Finally, we present minimum expected standards of clinical care for individuals with CACNA1C-Related Disorder or Timothy syndrome, with implications for long-term management and improved outcomes for affected individuals.
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.
This study aimed to summarize the current state of the science for "health service delivery-oriented outcomes" from nursing in genomics (2012-2025). Nurses can play a vital role in increasing access to genomic healthcare and improving outcomes for patients, families, and communities. We conducted a scoping review of the literature in four databases (2012-2025). Articles were categorized using the Cochrane Collaboration outcome domains and sub-domains to identify salient topics and synthesize findings. Of 11,646 retrieved articles, 66 publications reporting "health service delivery-oriented outcomes" were included for analysis. Identified articles spanned three sub-domains: "service delivery level," "related to research," and "societal or governmental." Within sub-domains, articles were further categorized into dimensions, the most prominent being "service utilization" under the "service delivery level" sub-domain. Studies were primarily from anglophone countries and near-evenly split into interventional and noninterventional studies. Studies reported that nurses working in multidisciplinary and/or interprofessional teams are a cost-effective means to increase access to genomic healthcare and reduce burden on genetic specialists. Nurses are incorporating genomics in various settings, including oncology, pharmacogenomics, genetic counseling, rare genetic diseases, and symptom science. Despite evidence of nurses contributing to health system delivery-oriented outcomes, evidence suggests that nurses are underutilized and underprepared in genomic healthcare. A significant barrier to integrating genomics into nursing practice is a lack of foundational knowledge and genomic competency across nursing education, clinical practice, and nursing policymakers. Nursing leadership spanning education, research, practice, and policy domains will be critical for integrating genomics in nursing practice and improving health system delivery-oriented outcomes.
The extension of transcatheter aortic valve replacement (TAVR) to younger patients with longer life expectancy has driven a shift in focus toward procedural optimization, with the goals of maximal clinical improvement, durable outcomes, maintained coronary access, and avoidance of permanent pacemaker implantation. A TAVR CODE framework including 4 key fluoroscopic parameters-coaxiality, orientation, depth, and expansion-has recently been proposed to standardize the intraprocedural evaluation of optimal transcatheter heart valve (THV) implantation. Systematic implementation of these concepts during TAVR is expected to improve valve performance and durability. This is hypothesized to improve afterload reduction, enhance left ventricular reverse remodeling, and confer increased and longer lasting clinical benefits. To date, procedural strategies to optimize TAVR outcomes have been largely based upon expert opinion, supported predominantly by mechanistic and retrospective studies. Ongoing randomized trials are evaluating the effects of systematic pre- and postdilatation during TAVR, the impact of same-volume double-tap techniques with balloon-expandable valves, and the effectiveness of different commissural alignment techniques. Meanwhile, intravascular ultrasound is under investigation as a tool to evaluate THV expansion to guide postdilatation, while technical consistency may be improved by innovative THV designs that promote symmetrical expansion, better fluoroscopic visualization, and robotic insertion systems using artificial intelligence. In this article, we detail the possible impact of implementing the TAVR CODE framework on THV function, durability, and clinical outcomes, and provide an expert perspective on procedural strategies to achieve optimal index TAVR outcomes, including management frameworks and position statements according to contemporary best practices.
The use of artificial intelligence (AI) is anticipated to transform mental health care. However, the rapid research growth in this field has outpaced coordinated frameworks, leaving research efforts fragmented, standards inconsistent, and safeguards for safety and ethics largely absent. This Position Paper outlines a coordinated roadmap to guide the responsible evaluation and implementation of AI in mental health, structured across four overarching priority domains that define near-term actions and longer-term strategic goals. Domain 1 (Strengthen safety and evidence standards) addresses deficits in clinical evidence and safety oversight, emphasising the need for robust comparative trials, standardised safety testing, and adaptive regulatory frameworks. Domain 2 (Centre ethics, equity, and patient voices) focuses on aligning AI development with real-world care contexts through transparent reporting, integration of patient perspectives throughout the AI lifecycle, and the development of representative datasets and equitable governance structures. Domain 3 (Evolve the role of the clinician) addresses challenges in clinical integration, including defining core competencies, clarifying clinical oversight and accountability, and conceptualising and trialling new workforce models. Domain 4 (Facilitate sustainable implementation and systems integration) targets barriers to real-world adoption, including the importance of interoperability with clinical infrastructure and the development of sustainable financing and implementation pathways. This roadmap should support coordinated action across stakeholders and ensure that AI-based mental health systems are developed and implemented in line with principles of safety, equity, evidence, and clinical accountability.
The evolution of plant genomics has been shaped by several pioneering milestones, beginning with the introduction of restriction fragment length polymorphism-based genetic linkage maps in the mid-1980s. Among the global contributors, Prof. Chittaranjan Kole stands as a distinguished figure whose work fundamentally shifted the trajectory of plant genomics and molecular breeding. This tribute highlights his scientific journey and groundbreaking contributions, from being the first Indian scientist to physically map and sequence a plant gene in barley to establishing the foundations of molecular cytogenetics, comparative genomics, and molecular evolution and phylogenetic relationships in plants. His landmark research on Brassica genomics, including high-resolution mapping, Mendelization of quantitative trait loci (QTLs), and innovative use of recombinant inbred lines, enabled unprecedented insights into trait evolution, stress biology, and genome homology between Brassica species and Arabidopsis. Prof. Kole's work on mapping genes and QTLs associated with flowering time, biotic stress resistance, abiotic stress tolerance, and genome evolution has provided a framework now integral to marker-assisted selection, genomic breeding, and climate-resilient crop development. This article offers a scholarly reflection on his pioneering contributions, establishing Prof. Kole as a founding architect of plant genomics research in India and one of its most influential contributors globally. This article discusses the life and achievements of Prof. Chittaranjan Kole, a world‐renowned scientist in plant genetics referred to as the “Father of Plant Genomics in India.” Prof. Kole was able to revolutionize agriculture through the application of “genomics,” or the study of an entire plant's code of genes, to learn how plants grow and live. Prof. Kole was also the first Indian scientist to physically map out and read the chemical code in a plant gene, specifically in barley plants. This was significant because it provided a blueprint on how scientists could identify important genes in plants. This was particularly significant in improving “Brassica” plants like mustard and cabbage because he was able to identify genes that protect plants from harmful diseases like “white rust,” as well as genes that allow plants to survive harsh weather conditions in winter. By discovering these “markers,” Prof. Kole was able to develop a system where plant breeders could select the best seedlings without having to wait for them to fully grow, a system that is now essential in developing plants that can withstand the effects of climate variabilities. Prof. Kole was also able to develop “agri‐nanotechnology” to improve crop production and establish international organizations to facilitate cooperation among scientists worldwide to address food security issues. Prof. Kole's decades‐long research in plant genetics were able to transform agriculture from traditional farming to a high‐tech “precision breeding.”.