The American College of Cardiology and American Heart Association recently updated their guidelines for dyslipidemia, which included recommending new risk calculators and thresholds, treatment targets, and treatment recommendations based on long-term risk. The purpose of this study was to quantify the population-level implications of the 2026 Dyslipidemia Guideline. Using data across 4 survey cycles from the 2011-2020 NHANES (National Health and Nutrition Examination Survey), we estimated the proportion and number of U.S. adults aged 20 years or older who were eligible for initiation of lipid-lowering therapy (LLT) under the 2026 vs 2018 guideline recommendations and the proportion meeting their 2026 treatment targets RESULTS: Among U.S. adults ≥20 years of age without atherosclerotic cardiovascular disease (ASCVD), with a low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL, and not on LLT (n = 165.4 million), 40.5% were eligible per the 2026 guideline vs 25.7% per the 2018 guideline, representing an additional 24.5 million adults. The largest contributor to the increase was the recommendation to consider statins in adults aged 30 to 59 years with a 30-year ASCVD risk ≥10% despite a 10-year risk <3%, based on which 15.6 million more adults would be eligible. In this age group, nearly twice as many qualify based on a 30-year ASCVD ≥10% vs 10-year ASCVD risk ≥3% (15.6 million vs 7.9 million). Among 39.1 million adults receiving LLT for a Class 1 indication, most (79.0%) had LDL-C above goal, including 91.1% of adults with ASCVD having LDL-C ≥55 mg/dL and 74.5% with LDL-C ≥70 mg/dL. Compared with the 2018 guideline, the 2026 American College of Cardiology/American Heart Association Multisociety Dyslipidemia Guideline substantially expanded the proportion of U.S. adults for whom statin therapy should be considered by extending recommendations to adults at high 30-year risk. Among those already on treatment, the vast majority remain above new guideline goals. Significant population-level shifts in statin initiation and therapy intensification will be needed to reach guideline goals at a national level.
The rise of older adults living alone with dementia demands a profound transformation in healthcare systems and societies worldwide. In Japan, where one in three households are occupied by only one person, this population faces elevated risks for adverse health outcomes, delayed diagnoses, and difficulties accessing critical services. In response, Japan launched the Study for Promoting Rights Protection in Older People Living Alone with Dementia, grounded in a human rights-based approach rather than traditional medical or social welfare models. This Forum article reflects on ten lessons from this initiative: expanding from service provision to building a society where dementia is integral to personhood; shifting from medical and social welfare approaches to a human rights lens; embracing living alone with dementia as viable; reframing care as social rather than individual or family responsibility; repositioning diagnosis from medical label to limited aspect of personhood; shifting from crisis-driven to preventive support; reframing dementia from individual deficit to need for improved environmental design; reframing complex cases from "difficult" individuals to inadequately met needs; supporting older adults' decision-making; and recognizing people with dementia as rights holders with state responsibility for protection.
A 57-year-old man with a history of congenital ventricular septal defect and bicuspid aortic valve with surgical repair of aortic coarctation presented with dyspnea and found to be in complete heart block with junctional escape rhythm necessitating pacemaker implantation. Pacemaker implantation in adult congenital heart disease and atrioventricular block requires preprocedural planning. Multimodality imaging is important in patients with complex septal anatomy, as it can reduce procedural difficulty and improve procedural safety by identifying optimal lead positioning strategies. Multimodality imaging can facilitate safer and more precise pacemaker implantation in adult patients with congenital heart disease with abnormal septal anatomy.
Given the unprecedented rise in glucagon-like peptide-1 receptor analogue (GLP-1RA) therapy over the past decade, we aimed to investigate potential unintended laryngeal manifestations. A retrospective cohort study was conducted using the TriNetX United States Collaborative Network. Adults with obesity on GLP-1RA medications (n = 617,296) from January 1, 2016 to December 3, 2025, were compared with controls (n = 3,503,102), excluding patients with head and neck neoplasms, head and neck radiation therapy, autoimmune diseases, airway disorders or acute respiratory conditions via ICD-10 and CPT codes. Laryngeal symptoms within 1, 3, and 6 months of initiation of GLP-1RA were assessed in propensity score-matched cohorts by age, sex, race, and ethnicity. Outcomes were reported as risk differences (RD) and odds ratios (OR) with 95% confidence intervals (CI). GLP-1RA therapy increased the 6-month risk of any laryngeal manifestations (OR 1.19, 95% CI 1.16-1.21; p < 0.0001). Higher odds were observed for cough (OR 1.46, p < 0.0001), foreign body sensation (OR 1.1.41, p < 0.001), and voice and resonance disorders (OR 1.19, p = 0.002). Across agents, exenatide, liraglutide, semaglutide, dulaglutide, and lixisenatide showed significant elevated 6-month risk of laryngeal manifestations (OR 1.16-1.91-1.48; p < 0.05), while albiglutide and tirzepatide did not. GLP-1RA/GIP use in adults is linked to higher rates of laryngeal symptoms, most notably cough and voice and resonance disorders. While absolute risk differences were small, the large number of affected individuals underscores the potential clinical and public health relevance of these findings, in the context of the rapidly growing prevalence of GLP-1RA/GIP use.
There is a potential link between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and depression in later life. This study aims to examine whether MASLD is associated with elevated clinically relevant depressive symptoms in community-dwelling older adults. This study utilised longitudinal data from a prospective cohort to quantify the association between MASLD at baseline and depressive symptom trajectories. MASLD, introduced by multinational liver societies to replace Non-Alcoholic Fatty Liver Disease (NAFLD), highlights the central role of metabolic dysfunction in the pathogenesis of steatotic liver disease. Depression trajectories were estimated across a median follow-up of 4.6 years (IQR: 0.1-7.1 years) and were identified as four distinct patterns of symptoms: 'non-depressed', 'subthreshold depression', 'persistent depression', and 'emerging depression'. Multivariable multinomial logistic regressions were performed to examine the association between baseline MASLD presence and membership of the depression trajectories, adjusting for sociodemographic and lifestyle factors, anthropometric indices, cognitive function, polypharmacy and the number of morbidities. Additional subgroup analyses were also performed. Of 9097 individuals (mean age 75.1 ± 4.2 years; 55.0% males), 2998 (33%) had MASLD at baseline. Participants with MASLD were significantly more likely to belong to the persistent depression trajectory (RRR = 1.13; 95% CI: 1.02-1.24) and the subthreshold depression trajectory (1.43; 1.22-1.67) than those without MASLD. This study shows that the presence of MASLD is significantly associated with an increased risk of a worse depression trajectory. In subgroup analysis, this relationship was particularly pronounced amongst females and among individuals with key cardiometabolic morbidities such as dyslipidaemia.
Ear, nose and throat (ENT) foreign body (FB) is common problem with significant morbidity and mortality. They are classified into organic or inorganic. Aerodigestive FBs are responsible for suffocation and death up to three years old with a 10% mortality up to 14 years old in Europe. Malaysia lacks local data that quantifies FB in dimensions to predict its risk. The study objectives were to determine the incidence of ENT FBs (paediatric and adult) in a Malaysian tertiary referral center; to determine the association between the FB types and factors contributing to its occurrence (largest dimension, volume, witnessed); to determine the treatment required; and association between hand dominance with ENT FBs. Prospective data of all children (<18 years old) and adults (≥18 years old) seen by the ENT physicians presenting with ENT foreign body were included over 12 months at Hospital Canselor Tuanku Muhriz (HCTM) from 1st February 2017 to 31st January 2018. All cases are seen by an ENT doctor (specialist and/or medical officer) during on-call, in hospital and outpatient's referrals. FB dislodged in the lower airways (trachea, bronchus and bronchiole) and upper gastrointestinal (GI) tract (oesophagus) were included. Exclusion criteria were FB dislodged in non-ENT orifices such as the stomach and beyond with no other ENT FBs. Bias was reduced by a proforma after obtaining an informed consent and taking the average of three measurements of FB dimensions. The incidence of ENT FB within HCTM was 3.5% (overall), 1.9% (organic), 1.6% (inorganic); 1.65% (children) and 1.85% (adults). Children have a mean age of 5.34 and adults 49.35 years. Among the patient factors; children FB are often inorganic (73.95%; plastic, metal, graphite), males predominant (56.5%), unwitnessed (66.67%), witnessed incidents were by adults (69.5%) at home (91.3%). Adult FB are often organic (77.1%; fish bone, cotton, tick), male to female ratio 1.4:1; not associated with occupation. Mackerel followed by red snapper and tilapia were common fish bones ingested. Common locations of FB among children and adults were throat (35.3%), ear (32.03%) and nose (26.14%). Less than one fifth required hospitalization due to aerodigestive FBs with 6 (72.7%) of hospitalised patients suffering complications of hypoxic brain injury, lung collapse, pneumonia, esophageal perforation and lacerations. Fifty-seven (37.25%) patients (adults predominant) required endoscopic removal under general or local anaesthesia. The side of ear and nose FB to hand dominance was significant (p<0.05). ENT FB are more common in the ear and nose in children; not witnessed, located in the oropharynx and occurred at home and during playtime. Organic FB and fish bones were common among adults in the Malaysian population. Aerodigestive FBs are associated with hospitalization, complications, requiring antibiotics and endoscopic intervention.
EvoDevo called homeotic genes "architect genes" because they "control" "body plans". The first metaphor involves purposefulness and brings finalism; the second one is cybernetic; the third one is idealistic/platonic. These are three ways of thinking that are incompatible with today's evolutionary theory. Using such ordering causal factors, EvoDevo partly stayed outside biology-and evolution as well-because in biology, order is not causal: it is a consequence that we need to explain. Natural selection is one of the concepts explaining the rise of apparent short-term biological order, or regularities. We no longer need the verb "to control" [Nijhout, Prog. Biophys. Mol. Biol., 169-170 (2022)]. Since genes are controlled [Noble, Interface Focus, 7 (2017)], just as much as they control, the notion of control in this context is not appropriate. It would be better to speak of "contribution". Natural selection and descent with modification, the two pillars of the Darwinian approach to life [Gayon, C. R. Palevol, 8 (2009)], are entering the soma. They are not restricted to the functioning of the adult soma, but also to the entire developing soma, avoiding "adultocentrism" [Minelli, Toward a Theory of Development (2014)]. The first pillar, natural selection within the body, anticipated by [Roux, Der Kampf der Teile im Organismus: Ein Beitrag zur Vervollständigung der Mechanischen Zweckmässigkeitslehre (1881); Roux, La lutte des parties dans l'organisme (2013)], but occulted during the past century [Heams, La lutte des parties dans l'organisme (2013b)], is now helping to explain cancer dynamics, aging, neurogenesis, etc. With the second pillar, it is now possible to construct the phylogeny of cells of a single developing organism, or to perform a phylogenetic analysis of metastases from a single patient. Ontogenesis and phylogenesis are no more two distinct processes: natural selection and descent with modification both contribute to explain both the developing individual and its stability, as well as the regularity of individuals of a same population from which we name species. The two pillars of evolutionary theory-descent with modification and natural selection-do occur within the developing organism itself and the resulting phenomenon is ontophylogenesis [Kupiec, L'ontophylogenèse. Évolution des espèces et développement de l'individu (2012)], which is actually studied by EvoDevo. L’EvoDevo a qualifié les gènes homéotiques de « gènes architectes » parce qu’ils « contrôlent » les « plans d’organisation ». La première métaphore est teintée de finalisme, la deuxième est cybernétique, la troisième est idéaliste/platonicienne, trois façons de penser incompatibles avec la théorie de l’évolution actuelle. En utilisant de tels facteurs causaux ordonnateurs, l’ÉvoDévo est restée en partie en dehors de la biologie — et de l’évolution également — car en biologie, l’ordre n’est pas causal, c’est une conséquence que nous devons expliquer. La sélection naturelle est l’un des concepts expliquant l’émergence d’un ordre biologique apparent à court terme, ou de régularités. Nous n’avons plus besoin du verbe « contrôler » [Nijhout, Prog. Biophys. Mol. Biol., 169–170 (2022)]. Comme les gènes sont autant contrôlés [Noble, Interface Focus, 7 (2017)] qu’ils contrôlent, la notion de contrôle à leur sujet n’est pas appropriée. Il vaudrait mieux parler de « contribution ». La sélection naturelle et la descendance avec modification, les deux piliers de l’approche darwinienne de la vie [Gayon, C. R. Palevol, 8 (2009)], entrent dans le soma. Sans se limiter au fonctionnement du soma adulte, ces deux concepts s’appliquent aussi à l’ensemble du soma en développement, évitant ainsi l’ « adultocentrisme » [Minelli, Toward a Theory of Development (2014)]. Le premier pilier, la sélection naturelle au sein du corps, anticipé par [Roux, Der Kampf der Teile im Organismus : Ein Beitrag zur Vervollständigung der Mechanischen Zweckmässigkeitslehre (1881) ; Roux, La lutte des parties dans l’organisme (2013)], mais occulté au cours du siècle dernier [Heams, La Lutte des Parties Dans l’organisme (2013b)], permet aujourd’hui de comprendre la dynamique du cancer, le vieillissement, la neurogenèse, etc. Grâce au deuxième pilier, il est désormais possible de construire la phylogénie des cellules d’un seul organisme en développement, ou d’effectuer une analyse phylogénétique des métastases d’un seul patient. L’ontogenèse et la phylogenèse ne sont plus deux processus distincts : la sélection naturelle et la descendance avec modification contribuent toutes deux à expliquer à la fois le développement de l’individu et sa stabilité, ainsi que la régularité des individus d’une même population à partir de laquelle nous nommons des « espèces ». Les deux piliers de la théorie de l’évolution — la descendance avec modification et la sélection naturelle — se produisent au sein même de l’organisme en développement et le phénomène résultant est l’ontophylogenèse [Kupiec, L’ontophylogenèse. Évolution des espèces et développement de l’individu (2012)], ce qu’étudie en réalité l’ÉvoDévo.
Postintensive care frailty impairs quality of life in survivors of severe illness. While anabolic hormone deficiency and prolonged inflammation are considered key physiologic mechanisms, specific features associated with frailty progression remain unclear. This study aimed to elucidate clinical characteristics associated with frailty deterioration following recovery from septic shock in older adults. Post hoc analysis of a randomized controlled trial. ICUs in Japan. Adults of 65 years or older with septic shock. Data were analyzed from a randomized controlled trial investigating optimal blood pressure targets in patients of 65 years or older with septic shock. Frailty at 90 days after intensive care was classified as no-to-mild, moderate, and severe based on the Clinical Frailty Scale (CFS) scores of less than or equal to 4, 5-6, and greater than or equal to 7, respectively. Baseline characteristics, treatments, and outcomes were compared across these frailty categories. Factors associated with postintensive care frailty were identified using ordinal logistic regression fitted with a generalized estimating equation model. Among 513 eligible patients, 339 patients survived to 90 days; 103 patients (30.4%) had no-to-mild frailty, 114 patients (33.6%) had moderate frailty, and 122 patients (36.0%) had severe frailty, respectively. Higher presepsis CFS scores (adjusted odds ratio [aOR], 2.03 [1.72-2.40] per 1-point increase; p < 0.001), higher sequential organ failure assessment (SOFA) scores (aOR, 1.16 [1.06-1.26] per 1-point increase; p < 0.001), and corticosteroid use (aOR, 1.72 [1.14-2.61]; p < 0.001) were independently associated with frailty. Subgroup analyses revealed that corticosteroid use was associated with frailty deterioration in patients with baseline frailty (CFS ≥ 5), whereas SOFA scores were associated with frailty in patients with tissue hypoperfusion (lactate, ≥ 2 mmol/L). Baseline frailty before sepsis, organ dysfunction severity, and corticosteroid therapy independently predict severe postintensive care frailty in older adults with septic shock.
Atoh7 is a transiently expressed developmental transcription factor that contributes to the generation of all seven major retinal cell types. Despite this broad lineage potential, Atoh7 is specifically required for retinal ganglion cell (RGC) formation and survival. In mice, a substantial proportion of RGCs arise from Atoh7-negative progenitors, suggesting potential nonautonomous roles for Atoh7 in RGC development. Although atoh7 function is conserved in zebrafish, the complete lineage, including the contribution to the RGC population, has not been fully defined. Here, we sought to determine the atoh7 retinal lineage in wild type and atoh7 mutant zebrafish. We generated atoh7:iCre transgenic zebrafish and paired them with the established ubi:Switch reporter to permanently label the atoh7 lineage. We validated transgene expression and lineage labeling using in vivo live imaging and immunohistochemistry in embryonic, larval, and adult retinas, as well as in select regions of the adult brain. The atoh7:iCre;ubi:Switch system accurately recapitulated endogenous atoh7 onset, with reporter expression persisting into adulthood. We found that 79% of RGCs in wild-type retinas arise from atoh7-positive progenitors, a greater proportion than previously reported in mice. Additionally, mutant retinas displayed a significant increase in atoh7 lineage+/Pax6+ amacrine cells and an increased number of Prox1+ bipolar cells. We also identified atoh7 lineage positive cells in other central nervous system (CNS) regions. Our findings reveal both atoh7 lineage positive and negative retinal cell types in zebrafish, including RGCs, providing a platform to study survival and cell fate mechanisms of atoh7 lineage negative RGCs during retinal development.
Dyspnea in adults with secundum atrial septal defect (ASD) is often attributed to shunt physiology, whereas coexisting airway disease may remain unrecognized. Conversely, clinically significant ASD may be overlooked in patients presenting with predominant respiratory symptoms, creating a bidirectional cardiopulmonary diagnostic blind spot. We retrospectively identified 8 adults (median age 55.5 years; 5 women) with secundum ASD (15-30 mm) and clinically significant airway disease through bidirectional cardiology-pulmonology referral (6 cardiology-to-pulmonology; 2 pulmonology-to-cardiology). Airway physiology was obstructive in 6, restrictive in 1, and mixed in 1, with bronchodilator reversibility in 5. Integrated cardiopulmonary evaluation and respiratory optimization improved symptom attribution and guided individualized management. Seven patients underwent transcatheter ASD closure (median device size, 38 mm), including fenestrated closure in 2 after balloon occlusion testing identified impaired left ventricular compliance; 1 deferred closure after symptomatic improvement with respiratory therapy alone. No procedural complications occurred, and 1 noncardiac death occurred 5 years after intervention. Dyspnea in adults with ASD may reflect combined cardiac and airway disease. Disproportionate symptoms should prompt integrated cardiopulmonary evaluation. Accurate symptom attribution underpins respiratory optimization and individualized ASD closure.
Young adulthood is a critical period for establishing lifelong health behaviours, yet oral health is often neglected. This study investigated factors associated with oral health-related quality of life (OHRQoL) among Malaysian university students. A cross-sectional survey was conducted among 395 undergraduate students aged 18 to 25 years. Data were collected using a structured questionnaire assessing sociodemographic characteristics, perceived oral health status, oral healthcare seeking behaviour, and OHRQoL via the short Malay version of the Oral Health Impact Profile (S-OHIP(M)). Multiple linear regression was used to identify predictors of OHRQoL. The prevalence of OHRQoL impact was 41.0%, with a mean S-OHIP(M) score of 9.15 (SD=6.39). Significant predictors of poorer OHRQoL included having at least one oral health problem, dissatisfaction with oral health status, and visiting the dentist due to an oral health issue. Dental and medical students reported significantly better OHRQoL compared to health sciences students. Oral health care seeking behaviour, although generally favourable, was not significantly associated with OHRQoL. OHRQoL among young adults is influenced by both subjective perceptions and behavioural patterns. Promoting routine dental visits and enhancing oral health awareness may improve quality of life outcomes. These findings inform strategies for preventive care and service delivery targeting young adult populations.
To investigate the association between net ultrafiltration (NUF) rate and fluid balance changes with 28-day mortality in critically ill patients receiving continuous renal replacement therapy (CRRT). Multicenter retrospective observational study. Data from two European mixed medical-surgical ICUs: University Hospital Bern, Switzerland, and Amsterdam University Medical Center, the Netherlands. Adult critically ill patients receiving CRRT for at least 24 hours. None. We studied 973 critically ill adults undergoing a total of 6914 days of CRRT. NUF rates and fluid balance changes were calculated from hourly data and categorized into four predefined groups. NUF rates were classified as no NUF, low (< 1.01 mL/kg/h), moderate (1.01-1.75 mL/kg/h), or high (> 1.75 mL/kg/h). Fluid balance change was stratified as negative (< -1.5 L/day), moderate negative (-1.5 to -0.5 L/day), neutral (-0.5 to 0.5 L/day), or positive (> 0.5 L/day). Using multivariable regression, random forest modeling, and mediation analysis, we observed no independent association between NUF rate and 28-day mortality after accounting for fluid balance. Mediation analysis suggested that the apparent survival advantage observed among patients with higher NUF rates was largely mediated through achievement of a more negative fluid balance, rather than a direct effect of NUF rate itself. In contrast, more positive fluid balance changes were linked to adverse clinical outcomes including 28-day mortality. In this two-center cohort of CRRT patients, NUF rate was not independently associated with mortality. Instead, the key determinant of outcome was fluid balance change. These findings suggest clinicians should not make NUF decisions in isolation, but rather should be using NUF as a means to achieve patient-specific fluid balance targets.
Diabetic peripheral neuropathy (DPN) among older people is associated with significant gait and balance impairments, postural instability, and an increased fall risk. Virtual reality (VR)-based interventions have been shown to be effective in improving balance and mobility; however, their design features and applicability for older people with DPN remain unclear. This systematic review was conducted to examine the effectiveness of VR systems on clinical outcomes in individuals with DPN and translate the findings into geriatric-specific VR design recommendations. A systematic review design was employed. Five electronic databases (Scopus, PubMed, CINAHL, Web of Science, and Embase) were systematically searched. Guided by the Synthesis Without a Meta-Analysis (SWiM) approach, a narrative synthesis was conducted. A total of eight studies met the inclusion criteria, with a pooled sample of 341 participants (mean age = 49 to 72). VR systems were primarily used as intervention modalities (6 of 8 studies). Most VR systems employed non-immersive, screen-based platforms with real-time visual biofeedback. Progression algorithms were clinician-guided rather than adaptive. VR-based interventions demonstrated consistent improvements in postural sway, mediolateral stability, and functional mobility measures in adults with DPN. VR systems, used as either intervention and assessment modalities, were found to be effective in assessing and improving balance and functional mobility in adults with DPN. Based on these findings, the SAFE STEP PLAN Framework, a geriatric-specific design guidance for VR-based and other technology-assisted rehabilitation interventions in DPN, was developed to inform the design, implementation, and clinical integration of technology-assisted interventions for older people.
Chronic idiopathic axonal polyneuropathy (CIAP) accounts for approximately 20%-30% of adult-onset axonal polyneuropathies. Pathogenic RFC1 repeat expansions have emerged as a frequent cause of idiopathic sensory neuropathy, but their recognition in routine clinical practice may be challenging, particularly in the presence of potentially confounding comorbidities. We aimed to determine the prevalence of pathogenic RFC1 repeat expansions in a well-defined CIAP cohort, characterize the associated clinical and electrophysiological phenotype, and evaluate whether coexisting well-controlled diabetes mellitus (DM) or monoclonal gammopathy of undetermined significance (MGUS) may hinder recognition of RFC1-related neuropathy. We performed a retrospective observational study of adult patients with CIAP followed at a tertiary neuromuscular unit. All patients underwent RFC1 genetic testing. Clinical and electrophysiological features were compared between RFC1+ and RFC1- patients in the full cohort and after exclusion of patients with DM or MGUS. Ninety patients met CIAP criteria and were analyzed. Twenty-four (27%) carried biallelic pathogenic AAGGG repeat expansions in RFC1, of whom 6 (25%) had coexisting DM or MGUS. Compared with RFC1- patients, RFC1+ individuals more frequently exhibited dysautonomic symptoms, unsteadiness, history of falls, need for walking support, chronic cough, impaired vibration sense in the upper limbs and up to the knees in the lower limbs, brisk upper-limb reflexes, mild cerebellar signs, an abnormal head-impulse test, and a positive Romberg's test. Most of these differences persisted after exclusion of DM or MGUS. Electrophysiological studies in RFC1+ patients showed widespread sensory nerve involvement, including the upper limbs, with relative motor sparing, whereas RFC1- patients exhibited a more typical length-dependent pattern. Biallelic AAGGG repeat expansions in RFC1 were identified in 27% of patients with CIAP. Specific clinical and electrophysiological features may help distinguish RFC1-related disease from other forms of CIAP and identify candidates for genetic testing, even in the presence of potentially confounding comorbidities such as well-controlled DM or MGUS.
p.(V142I)-associated variant transthyretin amyloid cardiomyopathy (ATTRv-CM) is biologically aggressive and predominantly affects individuals of African ancestry. A 51-year-old Nigerian man was diagnosed with double outlet right ventricle by the adult congenital heart disease service, although challenging social circumstances hindered adherence to clinic appointments. He re-established regular contact after 3 years and underwent workup for corrective surgery. Cardiac amyloidosis was suspected on repeat echocardiogram and confirmed on cardiac magnetic resonance and bone scintigraphy. Genetic sequencing later identified homozygosity for the p.(V142I) transthyretin variant. He was referred for emergency transplant assessment after developing cardiogenic shock. Unfortunately, he died despite receiving supportive therapies. Homozygous p.(V142I)-ATTRv-CM presents earlier and advances more aggressively than its heterozygous counterpart. This unusual case highlights the diagnostic pitfalls when genetics, adult congenital heart disease, and advanced heart failure intersect. In patients of African ancestry, a high index of suspicion for p.(V142I)-ATTRv-CM is needed to prompt early diagnosis and initiation of disease-modifying therapies.
Enterovirus D68 (EV-D68) has re-emerged over the past decade as a significant respiratory pathogen associated with severe respiratory disease and acute flaccid myelitis. Its circulation has typically followed a biennial pattern, with predominance in late summer and early fall, a pattern that was temporarily disrupted during the COVID-19 pandemic. Surveillance in 2025 revealed off-season circulation of EV-D68. This study describes the genomic characteristics of the 2025 EV-D68 viruses and the clinical features of affected patients. Between May and December 2025, remnant respiratory specimens positive for rhinovirus/enterovirus were screened for EV-D68 and subjected to whole-genome sequencing. Phylogenetic analyses were performed using maximum-likelihood methods. Recombination was assessed using subgenomic phylogenies, SimPlot similarity and BootScan analyses, and read-level inspection. Among 1,321 patients tested, 147 (11.1%) were EV-D68-positive, and 119 (81.0%) yielded complete genomes. EV-D68 positivity increased in July 2025, peaked in August (~21%), and remained elevated through September and October, exceeding levels observed in 2024. Patients had a median age of 36 years, with infections disproportionately affecting older adults. Phylogenetic analysis demonstrated exclusive circulation of subclade A2. Five genomes formed a distinct recombinant lineage (A2-Re). Subgenomic phylogenies showed clustering with A2 viruses in the P1 region and with B3 viruses in the P2-P3 regions. SimPlot and BootScan analyses identified a recombination breakpoint near the 2A/2B junction (~nt 3,700). The recombinant lineage was associated with temporally clustered cases in September-October. These findings demonstrate recombination between distinct EV-D68 subclades and underscore the importance of whole-genome surveillance for accurate viral characterization. Continued genomic monitoring is essential for detecting emerging variants with potential implications for transmissibility, pathogenicity, and public health preparedness.IMPORTANCEThis study highlights an increased off-season circulation of Enterovirus D68 (EV-D68) and a higher burden of disease in adults in 2025. The identification of a novel A2-B3 recombinant lineage provides evidence of ongoing viral evolution through recombination, a mechanism that may alter transmissibility, virulence, or immune responses. Detection of this lineage in temporally clustered cases suggests local transmission and underscores the potential for rapid spread of newly emerged variants. These findings emphasize the limitations of partial genomic approaches and the critical role of whole-genome sequencing in accurately characterizing circulating strains and identifying recombination events. Enhanced genomic surveillance is essential to detect emerging variants in real time, inform diagnostic assay performance, and support public health responses. Continued monitoring of EV-D68 evolution will be important for anticipating changes in disease burden, guiding clinical awareness, and strengthening preparedness for future outbreaks.
Self-care behaviour, motivation, and selfefficacy represent related but distinct dimensions of hypertension self-management. Previous Indonesian studies have generally examined self-care behaviour as the primary outcome or treated motivation and self-efficacy as its explanatory factors. Evidence describing the outcomespecific associations of sociodemographic and clinical characteristics with these three domains remains limited. This study examined the associations of selected sociodemographic and clinical characteristics with self-care behaviour, motivation, and self-efficacy among adults with hypertension. This analytical cross-sectional study included 120 adults with hypertension attending the Gianyar 1 Community Health Centre, Bali, Indonesia, between August and September 2024. Participants were selected from an eligible patient registry using simple random sampling. Self-care behaviour, motivation, and selfefficacy were measured using the validated Indonesian version of the High Blood Pressure Self-Care Profile. Bivariate comparisons were followed by three separate multiple linear regression models. The mean scores were 44.09 (95% confidence interval [CI] 42.44-45.74) for self-care behaviour, 44.64 (95% CI 42.56-46.72) for motivation, and 42.99 (95% CI 41.21- 44.78) for self-efficacy. The self-care behaviour model was statistically significant (R2=0.375; adjusted R2=0.304; p<0.001). Higher self-care behaviour scores were observed among participants aged 41-50 years and private-sector employees, whereas lower scores were observed among participants with no formal schooling, junior high school education, and a hypertension duration of 1-5 years. The motivation model was also statistically significant but had lower explanatory value (R2=0.186; adjusted R2=0.094; p=0.028). Participants aged 41-50 years had higher motivation scores, whereas those with junior high school education had lower scores. The overall self-efficacy model was not statistically significant. Associations were observed mainly for selfcare behaviour and motivation, whereas the examined characteristics did not collectively explain self-efficacy. These findings support individualised assessment of behavioural, motivational, and confidence-related needs in primary care. Causal relationships cannot be inferred from this cross-sectional study.
In adults with acute nephrotic syndrome (NS), physical function often declines; however, limited evidence on the efficacy and safety of exercise therapy leads to its avoidance due to fears of exacerbated proteinuria and renal deterioration. This study aimed to assess whether early exercise therapy enhances physical function without elevating risks of non-remission or worsening kidney function. This single-centre randomised controlled trial enrolled hospitalised adults receiving glucocorticoid therapy for NS. Participants were randomised (1:1) to exercise therapy or standard care. The primary outcome was peak oxygen uptake (peak VO2) at baseline and 6 weeks. The secondary outcome was non-remission at 6 weeks (proteinuria ≥0.3 g/day). Analyses used multiple imputation for missing data, analysis of covariance adjusted for baseline, and modified Poisson regression. Twenty-seven participants were recruited (early intervention, n = 13; standard care, n = 14). Peak VO2 increased significantly in the early exercise group (Δ = 3.45 mL/kg/min; 95% confidence interval [CI], 1.22-5.67) but not in the standard care group (Δ = 1.00 mL/kg/min; 95% CI, -1.14 to 3.14). Adjusted between-group difference at 6 weeks was 2.46 mL/kg/min (95% CI, -0.12 to 5.03). Risk ratio for non-remission was 0.673 (95% CI, 0.266-1.703), with no significant intergroup difference. Early exercise therapy in acute NS improved exercise tolerance clinically, although the primary outcome between-group difference was not statistically significant. No evidence indicated increased non-remission risk. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (registration number: UMIN000038250; registration date: October 9, 2019).
To assess the impact of primary care value-based payment implementation on low-value service use among Medicaid beneficiaries. On July 1, 2021, North Carolina Medicaid launched the Advanced Medical Home (AMH) program to improve care quality and coordination under managed care. Health plans are now required to include financial incentives for care coordination and performance in contracts with the highest-tier primary care practices (Tier 3 AMHs). Leveraging the tiered structure of the program and using a difference-in-differences design, we compared changes in low-value care utilization before and after the AMH rollout among beneficiaries attributed to Tier 3 AMHs versus those in lower-tier or non-AMH practices. We used North Carolina Medicaid institutional and professional claims, managed care encounters, and enrollment and provider files, supplemented with information on provider characteristics. The analytic sample included 33.6 million beneficiary-months, representing 1.34 million nonelderly adult beneficiaries and 7903 primary care practices. Beneficiaries attributed to Tier 3 AMH practices and comparison practices had similar baseline rates of low-value care, with imaging for plantar fasciitis (31.2% vs. 28.9%), head imaging for uncomplicated headache (14.8% vs. 14.5%), and back imaging for nonspecific low back pain (13.8% vs. 13.8%) being the most commonly used low-value care services. Although rates for many low-value services declined over time, adjusted difference-in-differences estimates were small in magnitude and not statistically significant for low-value care outcomes included in the study. The results suggest limited effectiveness of value-based payment reform in curbing low-value service use among Medicaid beneficiaries in North Carolina. However, more time may be needed to observe substantial effects, given the gradual nature of practice transformation. Strengthening financial and quality-based incentives, including specific low-value care benchmarks, also could enhance the program's effectiveness in reducing unnecessary care.
Shariah-compliant and ibadah-friendly hospitals have been established in the Malaysian healthcare system for nearly two decades to support the religious needs of Muslim patients. In parallel, the Islamic input in the medical program curriculum has been designed to train healthcare professionals, particularly doctors, to integrate Islamic principles into their medical expertise, as they are expected to incorporate Islamic values into their daily practice. However, the practice of doctors with this Islamic integrated medical curriculum has not been thoroughly investigated. Thus, to what extent they embodied the Islamic values within their practice and the challenges they faced in realising this is not known. Therefore, this study aimed to explore the experiences of doctors and patients related to the integration of Islamic principles within Shariahcompliant hospital services. A single-site qualitative case study design was employed, recruiting 20 doctors and 18 adult patients receiving treatment in the Orthopaedic wards and clinic of a Shariah-compliant teaching hospital. In addition, 19 relevant documents have been sampled and included. The study was conducted using multiple data collection methods including individual in-depth interviews, nonparticipant observations and document analysis between June 2023 and February 2024. The data analysis was done according to framework technique facilitated by NVivo software version 5. Four key themes emerged: (1) fulfilling religious and spiritual needs through clinical interactions and services; (2) practising therapeutic communication guided by Islamic values such as compassion, honesty, and patience; (3) upholding privacy, dignity, and autonomy in patient care; and (4) the importance of an effective training program and a sustainable working environment. Doctors expressed varying levels of confidence and consistency in applying Islamic principles, often influenced by personal understanding, workload, and institutional support. Patients generally appreciated the effort to integrate religious values but noted inconsistencies in delivery and expectations. This study highlights both the perceptions and actual practices of doctors in integrating Islamic principles into their clinical roles, as well as how patients perceive and respond to such efforts. While both groups value the integration of Islamic values, variations in interpretation and practice reveal gaps between the intended Shariahcompliant model and its implementation on the ground.