Canadian Medical Association Journal

BackgroundIn patients with atrial fibrillation (AF) and stable coronary artery disease beyond 1 year after percutaneous coronary intervention (PCI), oral anticoagulant monotherapy is guideline-recommended; however, its efficacy and safety in patients with complex PCI remain uncertain. MethodsWe conducted a post-hoc analysis of the randomized ADAPT AF-DES trial comparing NOAC monotherapy versus NOAC plus clopidogrel in AF patients [≥]12 months after second- or third-generation drug-eluting st...

Background Older adults' walking has so far been evaluated using standardised assessments of walking capacity within a clinical setting. By taking the evaluation out of the laboratory into the real world, this study provides first evidence of the ability of Digital Mobility Outcomes (DMOs) to detect changes over time and the Minimal Important Difference (MID) in patients after proximal femoral fracture (PFF). This will guide the implementation of DMOs in research and clinical care. Methods For t...

BackgroundVestibular complaints are common in older adults and are linked to imbalance and falls. Some older adults show impaired vestibular perception despite preserved peripheral-reflex ("vestibular agnosia"). Yet it remains unclear if vestibular agnosia is independently linked to imbalance and falls in otherwise healthy older adults. We therefore investigated the prevalence of vestibular agnosia in community-dwelling older adults, and examined its association to balance and prospective falls....

BackgroundIntrinsic capacity (IC) is a key marker of healthy ageing, which captures an individuals physical and mental capacities, measured across five domains: cognitive, locomotor, psychological, vitality, and sensory. Although genetic factors are known to influence both general IC and its individual domains, existing IC indices have been developed primarily using phenotypic data, without accounting for the underlying biological architecture across domains. In this study, we developed a multi-...

Gait variability is a critical functional indicator of dynamic balance and neurocognitive decline in health. Its translation into clinical practice is, however, challenged by a lack of age-related normative trajectories and reference values under real-world ecological settings. Furthermore, the conventional metrics used to estimate gait variability (Coefficient of Variation, CV; Standard Deviation, SD) have a fundamental methodological flaw: the inherent sensitivity of conventional metrics to th...

Nipah virus (NiV) is a sporadic yet extremely deadly zoonotic pathogen, with reported case fatality rates of 40%-75% in impacted areas. Prolonged incubation, documented relapse, and delayed-onset encephalitis following apparent recovery indicate that NiV dynamics are influenced by intricate temporal processes. However, mechanistic contributions of these processes to epidemic persistence remain poorly understood. In this study, we develop and analyze a delay differential equation model for NiV tr...

IntroductionAge-group specific disparities for dentalcare use persist in the United States. The COVID-19 led to delays in non-urgent dentalcare. We provide national estimates on dentalcare use and influencing factors for the U.S. population before and during the COVID-19. MethodsWe used nationally representative Medical Expenditure Panel Survey for over pre-COVID-19 years (2018-2019) and COVID-19 years (2020-2021) We estimated yearly survey-weighted trends in mean non-zero dental visits by age ...

The seasonal circulation of respiratory syncytial virus (RSV) in countries such as Japan, together with the transient nature of passive immunity conferred to infants via maternal vaccination or monoclonal antibody administration, may warrant a differential strategy for those born during the RSV inter-seasonal period. Maximal effectiveness may be achieved by deferring immunisation of this cohort from birth until entry into their first RSV season using catch-up administration of monoclonal antibod...

Individuals with chronic kidney disease (CKD) have higher rates of hip fracture and post-fracture mortality. Although they may develop age-related osteoporosis similar to those without CKD, they may also exhibit CKD-related metabolic bone disease (MBD), characterized by low, high, or mixed turnover at similar levels of bone mineral density (BMD). Because BMD does not provide information about turnover status, clinical decision-making is challenging. This study evaluated the associations between ...

INTRODUCTIONDementia reflects vascular and neurodegenerative processes in late life, yet studies often examine risks and outcomes individually. This study tested whether the cumulative burden of risks relates to structural brain pathology and cognition, and whether brain markers mediate these associations. METHODSCross-sectional data were drawn from 38,414 older adults in the National Alzheimers Coordinating Center database. A composite score summed ten binary risk factors: hypertension, diabet...

BackgroundRising kidney discard rates and uncertainty around accepting higher risk donor kidneys highlight the need for decision support tools that integrate donor and recipient factors and communicate risk in ways that are understandable and usable at the time of offer. Conventional indices (e.g., KDPI/KDRI) provide population level signals but do not deliver individualized, cognitively accessible information aligned with real time clinical workflows. ObjectiveTo describe how key transplant st...

IntroductionThere remains considerable debate as to the cause of the epidemic of Mesoamerican Nephropathy (MeN). We have previously reported early loss of estimated glomerular filtration rate (eGFR) as a surrogate for disease onset in a population-representative cohort study of young-adults at risk of disease from Northwest Nicaragua. Using a nested case-control approach we analysed urine and serum proteins surrounding this timepoint with the aim of gaining insight into the primary disease aetio...

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally-licensed COVID-19 vaccines. Its potential public health and economic impact, in adults [≥]60 years and high-risk 18-59 years, was modelled versus no vaccination and originally-licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with 1-year tim...

ObjectivesDigital biomarkers offer scalable screening for type 2 diabetes, yet adoption is stalled by uncertainty regarding economic viability. This study evaluates the cost-effectiveness and budget impact of digital screening compared to opportunistic screening from a Swiss payer perspective. MethodsA probabilistic Markov cohort model was developed to simulate at-risk Swiss adults (age [≥]45, BMI [≥]25 kg/m{superscript 2}) over a 40-year horizon. The model incorporates a digital attritio...

BackgroundQuadruple therapy, comprising an angiotensin receptor-neprilysin inhibitor (ARNI), {beta}-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 inhibitor (SGLT2i), is guideline-recommended for heart failure with reduced ejection fraction (HFrEF). However, uptake in Singapore remains low. This study evaluated the cost-effectiveness of scaling up quadruple therapy from the current 30% uptake to realistic (80%) and stretch (100%) targets. MethodsWe deve...

BackgroundThe Kidney Precision Medicine Project (KPMP) consortium aims to redefine chronic kidney disease (CKD) by integrating clinical, pathological, and molecular tissue data from kidney biopsies. Here, we demonstrate how biopsy data in CKD can clarify disease etiology and contribute to understandings of disease pathophysiology and clinical prognosis. MethodsThe KPMP is obtaining research kidney biopsies from individuals with CKD (defined as an estimated glomerular filtration rate [eGFR] < 60...

Adaptation to physiological stress is fundamental to health but varies widely among individuals. In humans, this heterogeneity is evident in markedly different gains in fitness in response to identical exercise training. The molecular determinants of this variable "trainability" remain poorly understood. Here we identify insulin-like growth factor binding protein-7 (IGFBP7), a senescence-associated secreted protein, as a circulating constraint on exercise adaptation. Plasma proteomics in older a...

Structured AbstractO_ST_ABSBACKGROUNDC_ST_ABSPatient reports are the standard when examining subjective cognitive decline (SCD). Recent research suggests that informant and clinician reports may also be associated with cognition. This study examined differences between patient, informant, and clinician definitions of SCD and their relationship to cognition. METHODSData from 4290 older adults (n=1690 normal controls, NC; n=840 mild cognitive impairment, MCI; n=1760 Alzheimers disease, AD) were e...

Biomarkers of aging, particularly DNA methylation-based clocks, have shown promise as tools to assess whether interventions may impact the rate of biological aging. Among possible interventions physical exercise has shown protective effects against many age-associated diseases, while time-restricted feeding (TRF), has shown metabolic benefits in preclinical models. The combined effect of exercise and TRF on aging biomarkers remains largely unexplored. In this 52-week four-armed, randomized, cont...

IntroductionPatients with type 2 diabetes mellitus (T2DM) are at increased risk of coronary artery disease and frequently undergo coronary angiography or percutaneous coronary intervention. Although risk factors for post-contrast acute kidney injury (PC-AKI) are well defined, effective preventive strategies remain limited. MethodsThis multicenter observational cohort study included 975 patients aged 18-75 years who underwent coronary angiography and/or percutaneous coronary intervention with io...