Blood services worldwide continue to face persistent challenges in recruiting and retaining voluntary, non-remunerated blood donors, particularly among younger populations. Over the past decade, communication strategies have shifted from traditional mass media to digital environments, where social media platforms, influencers, and online communities increasingly shape social norms, identity formation, and prosocial behaviour. These digital tools are now widely used to mobilise blood donors; however, the existing evidence base remains fragmented across disciplines, regions, and study designs. This scoping review aims to map and synthesise the available evidence on the role of social media, influencers, and online communities in blood donor recruitment and retention. It further seeks to identify key mechanisms underlying digital engagement, highlight knowledge gaps, and propose a digital sociology-informed framework to guide "next-generation" donor engagement strategies. A scoping review was conducted in accordance with PRISMA-ScR guidance. Major databases (PubMed, Scopus, Web of Science, PsycINFO, and CINAHL) and relevant grey literature were searched for publications from 2010 to March 2025. Eligible studies included empirical research and reviews examining (i) social media platforms, (ii) influencers, celebrities, or digital opinion leaders, and/or (iii) online communities or mobile and social applications used for blood donor recruitment or retention. Data were charted on study design, setting, digital platform, target population, intervention characteristics, and donor-related outcomes, and synthesised narratively. Evidence from broader eHealth and communication-intervention reviews was incorporated to contextualise social media within wider digital donor ecosystems. The body of evidence has expanded rapidly but remains methodologically and conceptually heterogeneous. Facebook's blood donation tools and associated engagement strategies were associated with modest yet consistent increases in total donations (approximately 4%) and first-time donations (around 19%) in multi-country quasi-experimental studies. Platforms such as WhatsApp, Twitter/X, and Instagram function primarily as "just-in-time" mobilisation channels, particularly in the Middle East and low- and middle-income countries, with high success in meeting urgent donation requests but limited longitudinal data on donor retention. Systematic reviews of eHealth interventions and mobile applications suggest that digital tools, including apps, SMS, and social media, can improve donation and repeat behaviour when interventions are personalised, interactive, and integrated into service workflows. Emerging literature highlights donors as digital advocates and explores how online communities foster donor identity, peer norms, and advocacy. In contrast, influencer-driven campaigns are largely documented in grey literature, and concerns persist regarding commercialisation, fear-based messaging, and misinformation. Social media and online communities have become central infrastructures for donor discovery, persuasion, and relationship-building, particularly among younger populations. However, the current evidence base is skewed toward high-income settings, single-platform interventions, and short-term outcomes. Future research should adopt theory-driven approaches, address equity and ethical concerns, and evaluate integrated, multi-platform strategies that link influencers, micro-communities, and formal blood services within coherent digital donor ecosystems.
Cochrane Rehabilitation and the World Health Organization (WHO) Rehabilitation Programme have collaborated to produce four Cochrane overviews of systematic reviews that synthesize current available evidence from health policy and systems research (HPSR) in rehabilitation. Each overview focuses on one of the four pillars of HPSR as identified by the Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy: delivery arrangements, financial arrangements, governance arrangements, and implementation strategies. This overview examined implementation strategies, defined by EPOC as interventions designed to bring about changes in healthcare organizations, the behavior of healthcare professionals, or the use of health services by healthcare recipients. This overview aimed to synthesize current evidence on implementation strategies in rehabilitation from a health policy and systems research (HPSR) perspective. Our series of four overviews have the following overarching objectives. • To offer a broad synthesis of the existing evidence on health policy and systems interventions' effects. • To direct end-users, including policymakers, towards systematic reviews that may address their health policy questions. • To identify current research gaps and set priorities for future primary HPSR. • To pinpoint the needs and priorities for new evidence syntheses where no reliable, up-to-date systematic reviews currently exist. We searched the Epistemonikos database, the Health Systems Evidence database, and EPOC Group systematic reviews to identify reviews published between 1 January 2015 and 17 November 2024. We applied no language limitations. We included Cochrane and non-Cochrane systematic reviews of randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) that evaluated the effectiveness of health policy and systems interventions for rehabilitation in health systems, specifically related to implementation strategies as defined in the EPOC taxonomy. All four overview teams collaborated to screen reviews and extract data. We used AMSTAR 2 to critically appraise the quality of the reviews. Results were analyzed descriptively and are based on reviews with ratings of high-to-moderate confidence, with low-confidence reviews reported separately. We identified 7882 systematic reviews, of which 15 met our inclusion criteria. Three reviews overlapped substantially with other reviews, and eight received low- or critically low-confidence ratings. Ultimately, four moderate- to high-confidence reviews contributed to the synthesis; two were Cochrane systematic reviews. Most primary studies were from high-income countries; none were from low-income countries. Most strategies targeting healthcare professionals (e.g. guideline dissemination, interactive workshops, opinion leaders, audit and feedback) or healthcare recipients (e.g. structured monitoring, telehealth support, counseling, motivational interviewing) included more than one component. Strategies targeting healthcare recipients' use of health services in cardiac rehabilitation may show small benefits in terms of participation (enrollment, adherence, completion), but effects on other outcomes are uncertain. The effects of strategies targeting older healthcare recipients via telehealth are uncertain. Strategies targeting healthcare professionals may have little to no effect on professional or patient and carer outcomes in stroke rehabilitation. For musculoskeletal conditions, there were no evidence-certainty ratings, so intervention effects are unclear. We found no reviews of strategies targeting health service organizations or specific types of rehabilitation practice. The evidence certainty was generally low; evidence of adverse events was missing or uncertain; and reporting on organizational, implementation, economic, and equity outcomes was scarce. Current evidence on implementation strategies in rehabilitation is limited, mostly of low certainty, and derived from high-income countries. Multicomponent, patient-targeted strategies may modestly improve cardiac rehabilitation participation, but effects in other areas remain uncertain. Further high-quality research using well-defined frameworks is needed, especially in low- and middle-income countries, to identify effective strategies and evaluate organizational, implementation, and equity outcomes. Future Cochrane overviews of reviews in HPSR should consider including a broader range of study designs, such as observational, qualitative, and mixed-methods evidence, to better capture evidence on implementation strategies in rehabilitation. This Cochrane review was funded by the Italian Ministry of Health (Ricerca Corrente). The funder played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The protocol was first published in the European Journal of Physical and Rehabilitation Medicine online on 27 January 2025. The manuscript was received on 11 November 2024 and was accepted on 26 November 2024. DOI 10.23736/S1973-9087.24.08833-6.
To synthesize evidence on how frailty in adults with systemic lupus erythematosus (SLE) is measured and to evaluate its associations with major clinical and patient-centered outcomes. We conducted a PROSPERO-registered systematic review (CRD42024600473) following PRISMA guidelines. PubMed, Scopus, Web of Science, and EBSCO were searched from inception to July 2025. Observational studies assessing frailty in adults with SLE and reporting prevalence and/or associations with organ damage, healthcare utilization, mortality, disability, or health-related quality of life (HRQoL) were included. Owing to heterogeneity in definitions and outcomes, findings were synthesized narratively. Seventeen studies were included. Frailty was measured using deficit-accumulation indices (e.g. the SLICC-Frailty Index), phenotype-based definitions (e.g. the Fried Phenotype), and performance measures, with prevalence ranging from approximately 7% to 46%. Frailty predicted faster accrual of organ damage (per 0.05 increase in SLICC-FI, adjusted IRR 1.20, 95% CI 1.14-1.27) and higher healthcare utilization (adjusted IRR 1.21, 95% CI 1.13-1.30). In the largest cohort (n=1,566), frailty was associated with increased mortality (adjusted HR 4.37, 95% CI 2.67-7.17) and showed a dose-response relationship. Frailty was also consistently linked to worse physical function, greater disability, and poorer HRQoL. Frailty is common in SLE and independently identifies patients at higher risk of adverse outcomes. Standardized definitions and longitudinal studies are needed to support risk stratification and targeted interventions. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect many organs and often requires long-term treatment with medications such as corticosteroids and immunosuppressants. Although advances in therapy have improved survival, many people with SLE continue to experience health complications and reduced quality of life.This study reviewed the scientific evidence about frailty, a condition marked by decreased strength, energy, and stress resistance, and its impact on people living with SLE. The researchers examined 17 studies from different countries that assessed how frailty is measured and its relationship to outcomes, including organ damage, hospitalizations, and mortality.The findings show that frailty is common in SLE, and frailty prevalence varied widely across studies and instruments. People with SLE who are frail are more likely to be hospitalized, stay longer in the hospital, and have a higher risk of death compared to those who are not frail. Frailty is also linked to faster progression of organ damage, poorer physical function, more pain and fatigue, lower bone strength, and a greater likelihood of fractures. These associations remain even when age, disease activity, and medication use are considered.Recognizing frailty early in SLE care may help doctors identify patients at higher risk and design personalized interventions, such as exercise, nutrition, and medication adjustments, to improve resilience, quality of life, and long-term outcomes.
Vaccination is an important tool to prevent infectious disease morbidity and mortality. Increased vaccine hesitancy and declining vaccination are contributing to larger infectious disease outbreaks. This review presents the current state of research and knowledge on vaccine hesitancy, focused on the United States (US). This review covers the history of vaccination and vaccine hesitancy, recent and ongoing outbreaks, and updates in understanding of vaccine hesitancy and use of new psychology-based tools to address it. Articles for inclusion were sourced from extant understanding of the vaccine hesitancy literature as well as PubMed searches to ensure appropriate context. Population-level outreach and effective communication about vaccines is a central component to addressing vaccine hesitancy and restoring and maintaining trust in the vaccination system. With new ways of understanding vaccine hesitancy rooted in the psychology of decision-making, there is a need for research into outreach, message development, and implementation, within the information and social media environment that allows even faster dissemination of mis- and dis-information. Balancing the rigor of communications and implementation research with the need for timely communications is a pressing challenge to be faced by public health and medical professionals when addressing vaccine hesitancy.
Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver condition linked to hepatic and extra-hepatic complications. This study aimed to estimate the risk of developing major adverse liver outcomes (MALO) and major adverse cardiovascular events (MACE) among patients with MASH. This retrospective cohort study used deidentified data from the Optum Clinformatics Data Mart Database to compare MALO (i.e. cirrhosis or associated complications, hepatocellular carcinoma, and liver transplant), modified 3-point MACE (i.e. nonfatal acute myocardial infarction (AMI), nonfatal stroke, and all-cause mortality), and expanded MACE (i.e. nonfatal AMI, nonfatal stroke, unstable angina (UA), coronary revascularization, or heart failure (HF) hospitalization) among adult patients newly diagnosed with MASH vs. patients without MASH. The risks of MALO, modified 3-point, and expanded MACE were estimated using descriptive methods (cumulative incidence and Kaplan-Meier estimator). Multivariable methods (Fine-Gray and Cox proportional hazards models) were used to describe the adjusted risk of 3-point MACE and MALO. MALO and MACE were assessed in 26,301 and 32,108 pairs of patients, respectively, in the matched cohorts with MASH and without MASH. After adjusting for baseline confounders, the risks for MALO (subdistribution hazard ratio, 6.78; 95% CI, 6.27-7.34) and modified 3-point MACE (hazard ratio, 1.67; 95% CI, 1.57-1.78) were significantly higher among patients with MASH vs. those without MASH. MASH was associated with significantly higher risks of MALO and MACE. This highlights the clinical burden of MASH and the need for early detection and management. Metabolic dysfunction-associated steatohepatitis (MASH) is a liver disease that affects people with other health issues related to the body’s metabolism, such as obesity and type 2 diabetes. This condition causes fat to build up in the liver and can lead to inflammation and scarring (fibrosis). In this study, we analyzed claims data to understand the association between MASH and the risk of liver, heart, blood circulation complications, and death. We compared patients with MASH with patients without MASH and grouped them by severity of liver scarring, determined by fibrosis stage. Our study found that people with MASH had a higher risk of death as well as worse liver, heart, blood circulation outcomes, such as worsening liver damage (cirrhosis), the need for a liver transplant, stroke, and heart attack. Additionally, people with more severe liver scarring (higher stage of fibrosis) had a higher risk of these outcomes compared with people with less severe liver scarring (lower stage of fibrosis). These results support the need for early detection and management of MASH.
Post-tuberculosis lung abnormality (PTLA) affects over 50-140 million TB survivors globally, creating a highly permissive environment for secondary fungal disease, particularly chronic pulmonary aspergillosis (CPA). CPA is now recognized as the most frequent and clinically significant Aspergillus-related complication of PTLA, contributing substantially to respiratory morbidity, misdiagnosis as TB relapse, and excess mortality in high TB-burden regions. Despite this, CPA remains largely absent from post-TB care pathways. This review synthesizes current evidence on CPA complicating PTLA, including epidemiology, pathogenesis, diagnosis, and management. Key findings include CPA prevalence of 7-23% in TB survivors, diagnostic utility of automated A. fumigatus-IgG assays, and characteristic chest CT-features. Randomized trials demonstrate the superiority of 12-month itraconazole, comparative efficacy of itraconazole and voriconazole, and the emerging role of posaconazole, isavuconazole, and nebulized amphotericin B are summarized. Field- and hospital-based diagnostic algorithms, refined treatment response criteria, and gaps in biomarker monitoring are addressed. CPA remains severely underdiagnosed due to overlapping features with TB, limited diagnostic access, and absence from national TB programs. Integrating CPA diagnostic bundles into national TB programs, standardizing serologic thresholds, ensuring antifungal stewardship, and developing validated composite response criteria are essential to improving outcomes in PTLA populations. Many people who recover from pulmonary tuberculosis (PTB) are left with long-term lung damage, and this damaged lung tissue can easily get infected by fungi, especially Aspergillus species, most commonly Aspergillus fumigatus. Chronic pulmonary aspergillosis (CPA) is the most common and serious fungal lung infection seen in people with old TB-related lung damage. Between 7% and 23% of TB survivors with lung damage may develop CPA, meaning millions of people worldwide are affected. CPA symptoms look very similar to TB symptoms, such as cough, weight loss, and blood in sputum. Because of this overlap, many people are wrongly treated again for TB instead of receiving antifungal treatment. A simple blood test that measures antibodies against Aspergillus is currently the best way to diagnose CPA. Adding tests for A. flavus can improve accuracy. Chest CT scans are extremely important because they clearly show cavities and fungal balls that help confirm the diagnosis. Treatment with the antifungal drug itraconazole for 12 months is more effective than shorter treatment, helping prevent relapse. Itraconazole and voriconazole work equally well, but itraconazole causes fewer side effects, making it the preferred initial treatment.In some cases, inhaled (nebulized) amphotericin B can help maintain improvement, especially in those with extensive disease despite treatment with oral azoles.Including CPA testing in national TB programs, improving access to blood tests, and training healthcare workers are essential steps to prevent missed diagnoses and improve patient outcomes.
Primary biliary cholangitis (PBC) is a rare chronic cholestatic disease that despite current therapy has significant ongoing unmet needs, including risks of cirrhosis and life-impairing symptoms. The current treatment approach is a step-up model, wherein first-line therapy, ursodeoxycholic acid (UDCA), is given for a minimum of 12 months before the addition of second-line therapy is considered for non-responding patients. This 'waiting to fail' approach, focused on the needs of low-risk patients, allows, we postulate, a key process of biliary epithelial cell (BEC) senescence to become established, driving accelerated bile duct loss and aggressive disease. Preclinical mouse modelling has shown that early use of the farnesoid X receptor agonist obeticholic acid (OCA), currently only used as second-line therapy following UDCA failure, reverses BEC senescence, changing the clinical course of disease. Here, we describe the design of the Optimising Primary thErapy in pRimAry biliary cholangitis (OPERA) trial. The aim of OPERA is to explore a new paradigm for disease-modifying treatment of PBC: risk-informed early treatment stratification, with patients at increased risk offered UDCA and OCA combination with the goal of complete biochemical remission. OPERA is a multicentre, randomised, double-blind, placebo-controlled trial of OCA in combination with UDCA, as first-line treatment for high-risk PBC. This is a multicentre trial in England, which will be undertaken in specialist clinics in secondary/tertiary referral centres (or as per local set up). These centres will be specialists in the area of PBC management and will manage patients from across their local region. OPERA will recruit and randomise 106 adults, within 6 months of PBC diagnosis, who are at an enhanced risk of non-response to standard first-line therapy, between either: (1) UDCA and OCA or (2) UDCA and matched placebo in a 1:1 ratio. The primary efficacy outcome measure is the percentage of participants showing normalisation of serum alkaline phosphatase and total bilirubin values at 26 weeks (disease remission). Favourable ethical opinion was received from London - Riverside Research Ethics Committee (reference: 22/LO/0878). Potential participants will be fully informed of their rights and the benefits and harms of the trial by the research team before giving informed consent to participate in the trial. Results will be disseminated in peer-reviewed publications, at national and international conferences, in peer-reviewed journals and to participants and the public (using lay language). ISRCTN17176388.
The first iteration of Good Practice for Conference Abstracts and Presentations (GPCAP), published in 2019, set the baseline for general recommendations and expectations for scientific conference abstracts and presentations. While individual conference guidelines must be followed, these recommendations aim to provide principles and best practice for pharmaceutical company-sponsored research. The purpose of conferences is the prompt communication of new data for dissemination and discussion within the context of short deadlines and relevant audiences. These updated recommendations aim to provide support for all individuals with a vested interest in the communication of scientific data at conferences. To provide principles and best practice covering the preparation and presentation of pharmaceutical-supported conference material. Feedback from the previous iteration, interviews with experts, and general revisions have been incorporated into these updated recommendations, aligning with Good Publication Practice (GPP) 2022. New sections have been added to cover topics that have risen in prominence since the first iteration: patient engagement, accessibility, and inclusivity; artificial intelligence; and enhanced content. Other sections cover authorship, copyright, citations, and encores, and have been updated accordingly. Conferences remain the key arena for communication and discussion of scientific data in real time as new developments within the scientific field continue to evolve rapidly. These updated recommendations provide principle-based, practical, insights-driven recommendations and suggestions on how to submit and present company-sponsored research with high standards and a commitment to consistency, transparency, and integrity for the scientific community. The aim is to make conferences the best they can be for all interested parties, within the context of pharmaceutical company-sponsored research.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality in the United States. Multi-target stool DNA (mt-sDNA) testing is a noninvasive, highly sensitive screening option, but its effectiveness is limited by workflow inefficiencies and suboptimal patient adherence. University of Washington Medicine (UWM) implemented Epic Aura, an electronic health record (EHR) interface that automates test ordering, patient outreach, and results communication, alongside shared decision-making (SDM) interventions. This study evaluated the impact of these implementations on mt-sDNA utilization and adherence. This retrospective cohort study used de-identified laboratory data from Exact Sciences for UWM patients aged ≥45 years. The pre-implementation period spanned December 5, 2022-December 4, 2023, and the post-implementation period December 5, 2023-December 4, 2024. The primary outcome was adherence, defined as return of a valid mt-sDNA kit within 365 days of shipment. Descriptive analyses and multivariable logistic regression compared adherence across periods and identified associated factors. A total of 125 pre-implementation and 1,160 post-implementation mt-sDNA shipments were analyzed. Utilization increased nearly 10-fold following implementation. Adherence improved from 64.0% pre-implementation to 79.1% post-implementation (p < .001), with faster kit return post-implementation (59.0% vs 48.8% within 30 days). Post-implementation was independently associated with higher adherence (adjusted odds ratio [aOR] = 1.98; 95% CI = 1.30-3.02; p = .002). Higher adherence was also associated with insurance type, higher household income, and digital outreach. EHR-integrated workflows combined with SDM were associated with marked improvements in mt-sDNA utilization, timeliness, and adherence, supporting scalable strategies to enhance CRC screening in real-world settings. Why was this study done?Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the United States, even though it can often be prevented through regular screening. Several screening options are available, including noninvasive stool-based tests. However, many eligible people do not complete these tests. Common barriers include complicated ordering processes, a lack of reminders, and limited discussion between patients and clinicians about screening choices. This study examined whether combining automated electronic health record tools with shared decision-making could improve completion of a stool-based CRC screening test.What did the researchers do?The University of Washington Medicine introduced two changes to routine care. First, they implemented an electronic system (Epic Aura) that allows clinicians to order the multi-target stool DNA (mt-sDNA) test directly from the medical record and automatically track results. Second, clinicians used shared decision-making during visits, discussing screening options with patients using standardized educational materials. Researchers compared test use and completion before and after these changes using de-identified laboratory data from adults aged 45 years and older.What did the study find?Test completion improved from 64% before the changes to 79% afterward. Patients also returned test kits more quickly, with most completing screening within 3 months. Even after accounting for differences in age, insurance, and income, patients were almost twice as likely to complete screening after implementation. Receiving digital reminders, such as emails or text messages, was associated with higher completion rates.What do these results mean?Integrating automated electronic workflows with shared decision-making can significantly improve CRC screening completion. These approaches may help health systems increase screening rates and support earlier cancer detection, although additional efforts may be needed to address remaining disparities.
Young-onset type 2 diabetes mellitus (T2DM) is a new health challenge with rising prevalence and significant morbidity. Persistent low-grade systemic inflammation and poor glycemic control lead to early occurrence of complications. The objective of this study is to evaluate the effectiveness of exercise-based programs on the neutrophil-lymphocyte ratio (NLR) and glycemic parameters, specifically fasting blood glucose (FBG) and glycated Hemoglobin (HbA1c), in individuals with young-onset T2DM. This randomized controlled trial involved a total of 84 individuals with T2DM between the ages of 18 and 40 years, randomly and equally assigned to either intervention or control groups. The participants in both groups received standard diabetic care. While the participants in the intervention group received an additional 12-week exercise-based program, consisting of a combination of aerobic and resistance training with moderate-to-vigorous intensity. NLR, HbA1c, and FBG were assessed at baseline and at 24 weeks. The glycemic parameters were also assessed at 12 weeks. A linear mixed-effects model was used to analyze the outcome measures with participants as random effects. We found a significant statistical difference between the intervention and control groups in NLR after 24 weeks (F = 107.3, p <0.001), also in HbA1c (F = 8.23, p <0.001) and FBG (F = 3.44, p <0.034) after 12 and 24 weeks, respectively. A 12-week exercise-based program consisting balanced regimen of aerobic and resistance training has a beneficial effect on NLR by reducing systemic inflammation and improving glycemic control in individuals with young-onset T2DM when compared to standard diabetic care alone. Clinical Trial Registry of India number: CTRI/2023/08/056051.
Osteoporosis is an important public health concern for postmenopausal women and needs effective treatments to alleviate the risk of fractures and associated complications. This study aimed to evaluate treatment compliance, persistence, satisfaction, and safety of the monthly single-pill treatment regimen of ibandronic acid 150 mg and cholecalciferol 22,400 IU in postmenopausal women with osteoporosis at risk for vitamin D insufficiency and fractures (The TÉSIS study). This non-interventional, multicenter, single-arm, prospective study included postmenopausal female patients from community pharmacies in Portugal. Two patient visits were conducted: the initial visit and the final follow-up visit after six months. Treatment compliance, persistence, and safety were evaluated using patient diaries, investigator notes, internal pharmacy sales information, and structured study questionnaires. Treatment satisfaction was assessed through the Osteoporosis Treatment Patient Satisfaction Questionnaire (OPSAT-Q). Of 230 enrolled patients, 211 completed both visits. At the final visit, the average treatment compliance (n = 180) was 98.7%, and 85.8% of patients remained persistent (n = 211). OPSAT-Q satisfaction scores (n = 202) were 81.69 (composite satisfaction score (CSS)-1) and 82.74 (CSS-2), indicating high satisfaction, favoring the treatment. Arthralgia and dyspepsia were the most frequently reported adverse reactions (6.2%). No significant differences were observed in treatment compliance, persistence, and satisfaction between first-time (n = 65) and previous users (n = 146) of the monthly single-pill treatment regimen of ibandronic acid 150 mg and cholecalciferol 22,400 IU. The monthly single-pill treatment regimen of ibandronic acid 150 mg and cholecalciferol 22,400 IU demonstrated high treatment compliance, persistence and patient satisfaction with a favorable safety profile and was well tolerated after six months of treatment.
Vascular malformations are chronic, often progressive disorders for which conventional procedures frequently provide incomplete control. Advances in molecular genetics have revealed recurrent pathway alterations that now enable mechanism-based pharmacologic treatment. This narrative review summarizes current and emerging targeted therapies for vascular malformations, including mTOR, PI3K, MEK, anti-angiogenic, and genotype-specific inhibitors. Vascular malformations - capillary, lymphatic, venous, and arteriovenous - are increasingly recognized as disorders driven by dysregulation of the PI3K - AKT - mTOR and RAS - MAPK - ERK pathways, supporting rational repurposing of targeted anticancer drugs. We discuss clinical evidence, limitations, and practical considerations for sirolimus, PI3K inhibitors, thalidomide, MEK inhibitors, and KRAS-directed agents, as well as emerging combination and intermittent strategies to balance efficacy and toxicity. The review is based on a structured PubMed/MEDLINE search up to December 2025, prioritizing original translational studies, prospective trials, and large clinical series. Targeted therapies are shifting management from procedure-centered to biology-guided care. Future progress depends on standardized molecular testing, patient-centered outcomes, and optimized treatment duration to achieve durable disease control with acceptable long-term toxicity.
Disordered mineral metabolism is associated with adverse outcomes in dialysis populations, but its prognostic significance in non-dialysis CKD is less well defined. This study evaluated elevated serum alkaline phosphatase (ALP) and hyperphosphatemia as predictors of mortality and renal outcomes in non-dialysis CKD. In this prospective cohort study, patients from a tertiary renal clinic were followed for >12 months. Elevated ALP was defined as >105 U/L in females or >130 U/L in males; hyperphosphatemia as phosphate >4.5 mg/dL. The primary outcome was mortality, and the secondary outcome was a composite endpoint (ESKD progression, dialysis initiation, or doubling of serum creatinine). Kaplan-Meier, log-rank, and Cox regression analyses were performed (STATA; p <.05). Among 360 patients (mean age 53.7 ± 13.9 years; follow-up 14 ± 4.2 months), elevated ALP was present in 31.7% and was associated with higher mortality (24.6% vs 8.9%, p <.001) and composite events (45.6% vs 33.9%, p = .03). Hyperphosphatemia occurred in 38.1% and was associated with increased mortality (21.2% vs 9.4%, p = 0.002) and composite outcomes (57.4% vs 25.6%, p <.001). Elevated ALP independently predicted mortality (HR = 2.37; 95% CI = 1.36-4.15; p = .002) but not composite outcomes. Hyperphosphatemia predicted both mortality (HR = 2.59; 95% CI = 1.47-4.57; p = .001) and composite events (HR = 2.55; 95% CI = 1.80-3.60; p <.001). Subgroup analyses demonstrated the highest mortality risk among patients with concurrent elevations in ALP and serum phosphate. Elevated ALP independently predicted mortality, while hyperphosphatemia predicted both mortality and CKD progression. Monitoring these biomarkers may improve risk stratification and guide future interventional studies. People with chronic kidney disease often develop mineral imbalances that affect health outcomes. This study investigated elevated serum alkaline phosphatase and hyperphosphatemia as predictors of mortality and composite renal outcomes in adults with non-dialysis CKD.Elevated ALP was associated with more than a twofold higher risk of death (adjusted HR = 2.44, 95% CI = 1.37–4.36; p <.002), while its association with composite renal outcomes was not statistically significant after adjustment (adjusted HR = 1.03, 95% CI = 0.72–1.47; p = .88). In contrast, hyperphosphatemia independently predicted both mortality (adjusted HR = 2.16, 95% CI = 1.13–4.14; p = .020) and composite renal outcomes (adjusted HR = 1.85, 95% CI = 1.26–2.73; p = .002).A key novel finding was the interaction between ALP and phosphate. The highest risk of death occurred when both ALP and phosphate were elevated, indicating that high phosphate amplifies the adverse prognostic impact of elevated ALP. Survival differences were minimal when phosphate levels were normal but became pronounced when phosphate was elevated.Overall, ALP and phosphate provide complementary prognostic information in non-dialysis CKD. Evaluating serum ALP and phosphate together may help identify patients at particularly high risk who could benefit from closer monitoring, targeted management, and strategies aimed at delaying CKD progression.
Intraoperative hypotension is a common occurrence in patients undergoing anaesthesia, although there is no standardised definition of hypotension. International consensus statements provide some guidelines for the management of intraoperative hypotension, but general clinical practice is unknown. We aimed to survey anaesthesiologists' values and preferences regarding intraoperative blood pressure management, including whether they would support future research on this topic. We conducted an international, online survey of routine practice and opinion. The target population was anaesthesiologists who regularly anaesthetise adult patients. Results are reported descriptively and in accordance with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS) checklist. A total of 1640 anaesthesiologists from 11 European countries participated in the survey. The majority of respondents were specialists (1322 of 1640, 80.6%, 95% CI 78.7-82.6). Almost all respondents worked in public hospitals (1613 of 1640, 98.4%). The overall response rate was 22.7%. Most respondents reported using absolute mean arterial pressure as their main unit of measurement to quantify hypotension (1098 of 1640, 67.0%, 95% CI 64.6-69.2). Respondents were most likely to initiate vasoactive treatment at a mean arterial pressure below 60 or 65 mmHg. Chronic arterial hypertension, traumatic brain injury and surgical procedures involving head-up positioning of the patient were the three most common scenarios where respondents would raise their threshold for treatment. Most respondents considered the establishment of safe intraoperative blood pressure thresholds a critical research question, and almost all respondents (1509 of 1640, 92.0%) indicated a willingness to randomise patients to specific blood pressure targets. For 72.9% (1196 of 1640), the lowest acceptable mean arterial pressure for randomisation was 60 mmHg. Respondents were also interested in the comparison of efficacy and safety of vasoactive agents, and the most sought-after comparison was phenylephrine versus noradrenaline (1252 of 1640, 76.3%). The willingness of respondents to administer these agents in peripheral venous access differed according to geography. In this international survey, mean arterial pressures of 60 or 65 mmHg were the most commonly reported blood pressure thresholds leading to initiation of treatment with vasoactive agents. Almost all respondents indicated patient groups for whom they would alter their treatment threshold, namely those suffering from chronic arterial hypertension, those undergoing surgery in a head-up position, and patients with traumatic brain injury. The majority of respondents supported future trials establishing optimal mean arterial pressure threshold and choice of vasoactive agent. We noticed a geographical variation in willingness to administer vasoactive agents in peripheral venous access. This survey of anaesthesiologists from European countries queried practitioner perceptions of blood pressure management in adults during anaesthesia with focus on hypotension. Queries and responses also concerned circumstances and blood pressure levels which clinicians report being willing to treat actively, and how they might do this practically.
Genetic variation in drug-metabolizing enzymes and transporters contributes to interindividual differences in drug efficacy and toxicity. While current pharmacogenomic practice typically assigns fixed functional categories to variant alleles, accumulating evidence shows that many variant alleles exert substrate-specific effects. We here summarize the current evidence for substrate-dependent functional variability across key pharmacogenes, including CYP2D6, CYP2C8, CYP2C9 and multiple uptake and efflux transporters, based on both experimental in vitro approaches and clinical pharmacokinetic analyses. We further evaluate the performance of existing computational variant-effect predictors and outline emerging structural, sequence-based, and representation-learning strategies for the prediction of substrate-specificity. Particular focus is placed on methodological gaps that currently prevent the prediction of substrate-specific effects and on the evolving technological landscape that may enable such capabilities. Substrate specificity of pharmacogenetic variations is clinically relevant and insufficiently captured by current functional annotations and prediction tools. We believe that new strategies based on integrative multimodal frameworks that combine structural descriptors, protein language-model embeddings, ligand features and high-quality experimental data have the potential to capture substrate-specific variant effects in the near future. These advances will provide exciting new opportunities to systematically evaluate variant function, which will benefit both drug development and precision medicine.
To describe real-world care models for teclistamab step-up dosing (SUD) and considerations for successful implementation among community-based practices and/or practices employing outpatient SUD. This mixed-methods study involved a survey, interviews, and roundtable discussion with US providers with real-world teclistamab experience. Survey topics included their practice's SUD model, adverse event management, and transition of care processes. Select survey respondents were interviewed to describe their practices' SUD models in-depth and barriers/facilitators to these models. A subsequent roundtable was held to provide additional context on current models. A total of 38 clinicians from unique practices completed the survey between March-August 2024; 76% worked at community-based practices and 66% had treated ≥5 multiple myeloma patients with teclistamab. Among survey participants, eight completed an interview and seven joined the roundtable. Among the 38 practices, 53% employed outpatient SUD, 26% inpatient SUD, and 21% referred out for SUD. Patient-level requirements for outpatient SUD (n = 20) included caregiver support (90%), proximity to administering site (70%), good performance status (65%), and low disease burden (30%). The top factors which triggered inpatient admissions were any grade immune effector cell-associated neurotoxicity syndrome (85%), grade ≥2 cytokine release syndrome (70%), and abnormal vital signs (60%). Over a quarter of practices (29%) used tocilizumab prophylactically. Outpatient teclistamab SUD has been successfully implemented in real-world practice for appropriately selected patients. This study provides insights into real-world outpatient SUD, including in community practices, to inform providers seeking to implement similar models to improve patient access while reducing cost and resource burden. Multiple myeloma is a blood cancer that develops in plasma cells. Teclistamab is a new treatment for patients whose multiple myeloma has returned or no longer responds to other therapies. Teclistamab can cause certain side effects and hence needs to be given in a special way called step-up dosing to lower the risk of these side effects. The risk of side effects and step-up dosing may cause some healthcare providers to feel unsure about how to use teclistamab safely. In this study, we asked doctors and other healthcare providers who have experience with using teclistamab about how they give this drug, manage the side effects, and handle patient care before and after the dosing. About half of the providers said that they give teclistamab in outpatient clinics to select patients (e.g. with caregivers or living close to the clinic). To help prevent side effects, preventive treatments are recommended but may be challenging to get coverage for these preventive treatments. However, recent changes in national guidelines supporting the use of preventive treatments have helped to reduce this challenge. More real-world information is needed to help community clinics to safely use teclistamab for their patients.
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a systemic vasculitis classified among the antineutrophil cytoplasmic antibody (ANCA) associated vasculitides. Eosinophils play a key role in its pathogenesis, with interleukin-5 (IL-5) being the most potent stimulator of their proliferation and activation. In recent years, treatment strategies have evolved with the introduction of biological agents targeting IL-5 or its receptor. This review summarizes the current evidence on the efficacy and safety of anti-IL-5 therapies, focusing on mepolizumab and benralizumab. A bibliographic search was conducted in PubMed, Web of Science, and Scopus, including studies of adults diagnosed with EGPA treated with anti-IL-5 therapies. The search was limited to articles published in the last 10 years in English or Spanish. Available data consistently show that these agents reduce corticosteroid requirements, lower eosinophil counts, and improve disease control. Regarding mepolizumab, real-world studies indicated that both 100 mg and 300 mg doses are equally effective, while the influence of ANCA status on treatment response remains controversial. Otorhinolaryngologic relapses have also been reported. Benralizumab 30 mg every 4 weeks showed remission rates comparable to mepolizumab, although further research is needed to determine the optimal dosing regimen. Overall, anti-L-5 therapies represent an effective and safe option for EGPA. Future research should focus on larger, multicenter trials to clarify the pathophysiology of the disease and facilitate the identification of predictive biomarkers, leading for personalized therapeutic strategies.
To describe the clinical characteristics, treatment approaches, and disease burden among older people with obesity disease (PwOD) in Japan. Secondary data from the Japanese cohort of the real-world, cross-sectional Adelphi Obesity Disease Specific Programme survey (July-December 2022) were analyzed. Physician's and PwOD's self-reported responses, including quality of life based on the Short Form Health Survey Version 2.0 (SF-36v2.0) and activity impairment from the Work Productivity and Activity Impairment (WPAI) questionnaire, were described by age group (<65 years, ≥65 years, and ≥75 years). Lower SF-36v2.0 scores (<45) and higher percentages in the WPAI questionnaire indicate greater impairment. Physicians (n = 101) provided data for 442 PwOD; 61 PwOD completed self-reported questionnaires. Older PwOD mainly consulted internal medicine physicians (≥65 years [45%] and ≥75 years [70%]). Common weight loss approaches across groups were: diets recommended and supervised by a healthcare provider (HCP)/dietitian/nutritionist/health coach; PwOD's own diet and exercise regime; and prescription obesity management medications. Physicians prioritized non-older PwOD for weight loss surgery or new weight loss drugs. In older PwOD, mean SF-36v2.0 physical component and bodily pain scores, and activity impairment were 34.5 (SD 12.8), 41.5 (SD 7.6), and 33.3% (SD 29.6%), respectively. Major weight loss goals in older PwOD were reducing joint pain and exercising regularly. Older Japanese PwOD faced physical impairments and were generally treated with lifestyle interventions by internal medicine physicians rather than specialists such as endocrinologists/diabetologists. HCPs should recognize obesity disease and obesity-related health disorders and provide appropriate medical care tailored to the specific needs of older PwOD.
HP-3070, the first asenapine transdermal system (patch), is indicated for adults with schizophrenia. The US Food and Drug Administration recommends analyzing clinical outcome data by using meaningful score difference (MSD) and meaningful score regions (MSRs) to determine what score changes are clinically meaningful to patients. This post hoc analysis aimed to determine the MSD and MSRs in Positive and Negative Syndrome Scale (PANSS) total score from the pivotal phase 3 study of HP-3070. Clinician-Rated Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) scores were used as anchors to quantify improvement from baseline to Week 6 in PANSS total score. The following were identified: MSD-change and percentage change in PANSS for ≥50% of responders (CGI-I=1,2) and MSRs-change and percentage change in PANSS by baseline CGI-S for 25th and 75th percentiles of responders. In total, 616 patients were evaluated. The mean (SD) baseline PANSS total score was 96.6 (9.5). MSD of change in PANSS score was -30 points. MSDs of percentage change in PANSS scores were -32% and -46% based on calculations without and with adjustment for the scale's minimum score, respectively. For all responders defined as CGI-I=1 or 2, MSRs of change in PANSS score ranged from -37 to -24. MSRs of percentage change in PANSS score ranged from -39% to -25% without adjustment and -57% to -37% with adjustment. The MSD and MSRs provide an estimate of expected treatment effect on schizophrenia patients in a population and serve as a threshold to identify individual patients with clinically meaningful improvement. These results contribute to the ongoing discussion of what constitutes a clinically meaningful response in patients with an acute episode of schizophrenia and provide an estimate of the expected treatment effect of HP-3070.
Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are among the backbones of treatment for relapsed/refractory multiple myeloma (RRMM). Beyond current standard-of-care regimens, the roles of mAbs/ADCs are evolving associated with advances in first-line therapy, emerging data on additional regimens, and developments with immunotherapies and other novel agents. We review mechanisms of action, efficacy, real-world effectiveness, and key aspects of the safety profiles of daratumumab, isatuximab, elotuzumab, and belantamab mafodotin in RRMM. We consider efficacy in patient subgroups and the challenges of treatment sequencing and highlight new antigen targets and mAb/ADC therapies under investigation. We searched the published literature with PubMed and congress abstracts using drug names or classes and 'myeloma.' The widespread use of daratumumab and isatuximab in first-line therapy and evolving roles of CAR T-cell therapies and bispecific antibodies are reshaping RRMM treatment. mAb/ADC-based regimens remain key options in this setting, offering practical, effective, and tolerable approaches for real-world practice. Ongoing research will inform individualized treatment choices and rational sequencing of therapies, with a need for immune-based biomarkers and biologic profiling to enable optimal, integrated use of mAbs, ADCs, CAR T-cell therapies, and bispecific antibodies to further improve outcomes for patients with RRMM.