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1.
Int J Cancer ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221990

ABSTRACT

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (ptrend = .003) and cumulative exposure (ptrend = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.

2.
Cell Genom ; 4(8): 100627, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39096913

ABSTRACT

Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.


Subject(s)
Mutation , Urinary Bladder Neoplasms , Xeroderma Pigmentosum Group D Protein , Humans , Urinary Bladder Neoplasms/genetics , Xeroderma Pigmentosum Group D Protein/genetics , Prognosis
3.
Med Eng Phys ; 130: 104202, 2024 08.
Article in English | MEDLINE | ID: mdl-39160016

ABSTRACT

Measuring the kyphotic angle (KA) and lordotic angle (LA) on lateral radiographs is important to truly diagnose children with adolescent idiopathic scoliosis. However, it is a time-consuming process to measure the KA because the endplate of the upper thoracic vertebra is normally difficult to identify. To save time and improve measurement accuracy, a machine learning algorithm was developed to automatically extract the KA and LA. The accuracy and reliability of the T1-T12 KA, T5-T12 KA, and L1-L5 LA were reported. A convolutional neural network was trained using 100 radiographs with data augmentation to segment the T1-L5 vertebrae. Sixty radiographs were used to test the method. Accuracy and reliability were reported using the percentage of measurements within clinical acceptance (≤9°), standard error of measurement (SEM), and inter-method intraclass correlation coefficient (ICC2,1). The automatic method detected 95 % (57/60), 100 %, and 100 % for T1-T12 KA, T5-T12 KA, and L1-L5 LA, respectively. The clinical acceptance rate, SEM, and ICC2,1 for T1-T12 KA, T5-T12 KA, and L1-L5 LA were (98 %, 0.80°, 0.91), (75 %, 4.08°, 0.60), and (97 %, 1.38°, 0.88), respectively. The automatic method measured quickly with an average of 4 ± 2 s per radiograph and illustrated how measurements were made on the image, allowing verifications by clinicians.


Subject(s)
Machine Learning , Scoliosis , Humans , Scoliosis/diagnostic imaging , Adolescent , Child , Radiography , Image Processing, Computer-Assisted/methods , Automation , Kyphosis/diagnostic imaging , Female , Male , Neural Networks, Computer , Lordosis/diagnostic imaging
4.
Environ Pollut ; 361: 124717, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39147225

ABSTRACT

The domestic combustion of locally sourced smoky (bituminous) coal in Xuanwei and Fuyuan counties, China, is responsible for some of the highest lung cancer rates in the world. Recent research has pointed to methylated PAHs (mPAHs), particularly 5-methylchrysene (5MC), within coal combustion products as a driving factor. Here we describe measurements of mPAHs in Xuanwei and Fuyuan derived from controlled burnings (i.e., water boiling tests, WBT, n = 27) representing exposures during stove use, and an exposure assessment (EA) study (n = 116) representing 24 h weighted exposures. Using smoky coal has led to significantly higher concentrations of known and likely human carcinogens than using smokeless coal, including 5MC (3.7 ng/m3 vs. 1.0 ng/m3 for EA samples and 100.8 ng/m3 vs. 2.2 ng/m3 for WBT samples), benzo[a]pyrene (38.0 ng/m3 vs. 7.9 ng/m3 for EA samples and 455.3 ng/m3 vs. 12.0 ng/m3 for WBT samples) and 7,12-dimethylbenz[a]anthracene (1.9 ng/m3 vs. 0.2 ng/m3 for EA samples and 47.7 ng/m3 vs. 0.6 ng/m3 for WBT samples). Mixed effect models for both EA samples and WBT samples revealed clear variation in mPAHs concentrations depending on smoky coal source while stove ventilation was consistently found to reduce measured concentrations (by up to nine fold and 65 fold for EA and WBT samples respectively when using smoky coal). Fuel type had a larger influence on mPAHs concentrations than stove type. These findings indicate that users of smoky coal experience exposure to many PAHs, including known and suspected human carcinogens (especially during cooking activities), many of which are not routinely tested for. Collectively, this provides insights into the potential etiologies of lung cancer in the region and further highlights the importance of targeting clean fuel transitions and stove refinements as the final goal for reducing household air pollution and its associated health risks.

5.
bioRxiv ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39211153

ABSTRACT

Insect diversification has been catalyzed by widespread specialization on novel hosts - a process underlying exceptional radiations of phytophagous beetles, lepidopterans, parasitoid wasps, and inordinate lineages of symbionts, predators and other trophic specialists. The strict fidelity of many such interspecies associations is posited to hinge on sensory tuning to host-derived cues, a model supported by studies of neural function in host-specific model species. Here, we investigated the sensory basis of symbiotic interactions between a myrmecophile rove beetle and its single, natural host ant species. We show that host cues trigger analogous behaviors in both ant and symbiont. Cuticular hydrocarbons - the ant's nestmate recognition pheromones - elicit partner recognition by the beetle and execution of ant grooming behavior, integrating the beetle into the colony via chemical mimicry. The beetle also follows host trail pheromones, permitting inter-colony dispersal. Remarkably, the rove beetle also performs its symbiotic behaviors with ant species separated by ~95 million years, and shows minimal preference for its natural host over non-host ants. Experimentally validated agent-based modeling supports a scenario in which specificity is enforced by physiological constraints on symbiont dispersal, and negative fitness interactions with alternative hosts, rather than via sensory tuning. Enforced specificity may be a pervasive mechanism of host range restriction of specialists embedded within host niches. Chance realization of latent compatibilities with alternative hosts may facilitate host switching, enabling deep-time persistence of obligately symbiotic lineages.

6.
Ann Plast Surg ; 93(3): 389-396, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39150855

ABSTRACT

BACKGROUND: Fat grafting is a highly versatile option in the reconstructive armamentarium but with unpredictable retention rates and outcomes. The primary outcome of this systematic review was to assess whether secondary mechanically processed lipoaspirate favorably enhances the vasculogenic potential of fat grafts when compared to unprocessed lipoaspirate or fat grafts prepared using centrifugation alone. The secondary outcome was to assess the evidence around graft retention and improved outcomes when comparing the aforementioned groups. METHODS: A search on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted up to February 2022. All human and animal research, which provided a cross-comparison between unprocessed, centrifuged, secondary mechanically fragmented (SMF) or secondary mechanically disrupted (SMD) fat grafts, was included. RESULTS: Thirty-one full texts were included. Vasculogenic potential was assessed by quantification of angiogenic growth factors and cellular composition. Cellular composition of mesenchymal stem cells, perivascular stem cells, and endothelial progenitor cells was quantified by fluorescence activated cell sorting (FACS) analysis. Fat graft volume retention rates and fat grafting to aid wound healing were assessed. Although the presence of industry-funded studies and inadequate reporting of methodological data in some studies were sources of bias, data showed SMF grafts contain an enriched pericyte population with increased vascular endothelial growth factor (VEGF) secretion. Animal studies indicate that SMD grafts may increase rates of fat graft retention and wound closure compared to centrifuged grafts; however, clinical studies are yet to show similar results. CONCLUSIONS: In this systematic review, we were able to conclude that the existing literature suggests mechanically processing fat, whether it be through fragmentation or disruption, improves vasculogenic potential by enhancing angiogenic growth factor and relevant vascular progenitor cell levels. Whilst in vivo animal studies are scarce, the review findings suggest that secondary mechanically processed fat enhances fat graft retention and can aid with wound healing. Further clinical studies are required to assess potential differences in human studies.


Subject(s)
Adipose Tissue , Lipectomy , Humans , Adipose Tissue/transplantation , Lipectomy/methods , Neovascularization, Physiologic/physiology , Graft Survival , Animals
7.
Cureus ; 16(7): e63968, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39104979

ABSTRACT

INTRODUCTION: The regional hand trauma service in Greater Manchester, United Kingdom, underwent significant reorganisation early in the COVID-19 pandemic, with a shift from predominantly general anaesthesia (GA) procedures to the adoption of a Wide-Awake Local Anaesthetic No Tourniquet (WALANT) technique. We implemented strategies targeted towards optimising patient experience, largely applicable to most healthcare settings. METHODS: Four domains were explored: (i) compliance in timing to nationally agreed treatment guidelines, (ii) the role of patient information leaflets, (iii) the introduction of a post-operative analgesia protocol, and (iv) broadly evaluating the environmental impact following the implementation of a same-day 'see and treat' service. RESULTS: Following reorganisation to a predominantly WALANT service, we observed an increase in compliance with nationally agreed standards for the treatment of common hand injuries. Patient education and peri-operative counselling reduced anxiety, whereas post-operative pain was better managed with the introduction of an analgesic protocol. Using a travel carbon calculator, it can be inferred that there are significant reductions in carbon emissions generated when patients are evaluated and treated on the same day as their clinical presentation. CONCLUSIONS: It is widely acknowledged that WALANT benefits patients and the healthcare system. We contemplated whether further incremental changes in clinical practice could further improve patient experience. Given our findings, we advocate a multi-modal approach with a greater focus on patient outcomes (trials are currently underway, e.g., WAFER) supplemented by universally accepted validated patient-reported outcome measures (PROMs).

9.
Eur Spine J ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987512

ABSTRACT

PURPOSE: Ultrasonography for scoliosis is a novel imaging method that does not expose children with adolescent idiopathic scoliosis (AIS) to radiation. A single ultrasound scan provides 3D spinal views directly. However, measuring ultrasonograph parameters is challenging, time-consuming, and requires considerable training. This study aimed to validate a machine learning method to measure the coronal curve angle on ultrasonographs automatically. METHODS: A total of 144 3D spinal ultrasonographs were extracted to train and validate a machine learning model. Among the 144 images, 70 were used for training, and 74 consisted of 144 curves for testing. Automatic coronal curve angle measurements were validated by comparing them with manual measurements performed by an experienced rater. The inter-method intraclass correlation coefficient (ICC2,1), standard error of measurement (SEM), and percentage of measurements within clinical acceptance (≤ 5°) were analyzed. RESULTS: The automatic method detected 125/144 manually measured curves. The averages of the 125 manual and automatic coronal curve angle measurements were 22.4 ± 8.0° and 22.9 ± 8.7°, respectively. Good reliability was achieved with ICC2,1 = 0.81 and SEM = 1.4°. A total of 75% (94/125) of the measurements were within clinical acceptance. The average measurement time per ultrasonograph was 36 ± 7 s. Additionally, the algorithm displayed the predicted centers of laminae to illustrate the measurement. CONCLUSION: The automatic algorithm measured the coronal curve angle with moderate accuracy but good reliability. The algorithm's quick measurement time and interpretability can make ultrasound a more accessible imaging method for children with AIS. However, further improvements are needed to bring the method to clinical use.

10.
Eur J Heart Fail ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023208
11.
Sci Adv ; 10(29): eadm9577, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39028815

ABSTRACT

Pausing of RNA polymerase II (Pol II) at transcription start sites (TSSs) primes target genes for productive elongation. Coincidentally, DNA double-strand breaks (DSBs) enrich at highly transcribed and Pol II-paused genes, although their interplay remains undefined. Using androgen receptor (AR) signaling as a model, we have uncovered AR-interacting protein 4 (ARIP4) helicase as a driver of androgen-dependent transcription induction. Chromatin immunoprecipitation sequencing analysis revealed that ARIP4 preferentially co-occupies TSSs with paused Pol II. Moreover, we found that ARIP4 complexes with topoisomerase II beta and mediates transient DSB formation upon hormone stimulation. Accordingly, ARIP4 deficiency compromised release of paused Pol II and resulted in R-loop accumulation at a panel of highly transcribed AR target genes. Last, we showed that ARIP4 binds and unwinds R-loops in vitro and that its expression positively correlates with prostate cancer progression. We propose that androgen stimulation triggers ARIP4-mediated unwinding of R-loops at TSSs, enforcing Pol II pause release to effectively drive an androgen-dependent expression program.


Subject(s)
Androgens , Prostatic Neoplasms , R-Loop Structures , RNA Polymerase II , Receptors, Androgen , Humans , Androgens/metabolism , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , RNA Polymerase II/metabolism , RNA Polymerase II/genetics , Cell Line, Tumor , DNA Topoisomerases, Type II/metabolism , DNA Topoisomerases, Type II/genetics , Transcription, Genetic , DNA Breaks, Double-Stranded , Transcription Initiation Site , Gene Expression Regulation, Neoplastic , Protein Binding , Transcriptional Activation
12.
J Clin Invest ; 134(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949020

ABSTRACT

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, X inactivation, genes escaping X inactivation, sex hormones, and life history.


Subject(s)
Epigenesis, Genetic , Neoplasms , Sex Characteristics , Humans , Female , Neoplasms/genetics , Male , Animals , X Chromosome Inactivation , Gonadal Steroid Hormones/metabolism , Genomic Imprinting
13.
Sensors (Basel) ; 24(14)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39066103

ABSTRACT

As Canada's population of older adults rises, the need for aging-in-place solutions is growing due to the declining quality of long-term-care homes and long wait times. While the current standards include questionnaire-based assessments for monitoring activities of daily living (ADLs), there is an urgent need for advanced indoor localization technologies that ensure privacy. This study explores the use of Ultra-Wideband (UWB) technology for activity recognition in a mock condo in the Glenrose Rehabilitation Hospital. UWB systems with built-in Inertial Measurement Unit (IMU) sensors were tested, using anchors set up across the condo and a tag worn by patients. We tested various UWB setups, changed the number of anchors, and varied the tag placement (on the wrist or chest). Wrist-worn tags consistently outperformed chest-worn tags, and the nine-anchor configuration yielded the highest accuracy. Machine learning models were developed to classify activities based on UWB and IMU data. Models that included positional data significantly outperformed those that did not. The Random Forest model with a 4 s data window achieved an accuracy of 94%, compared to 79.2% when positional data were excluded. These findings demonstrate that incorporating positional data with IMU sensors is a promising method for effective remote patient monitoring.


Subject(s)
Activities of Daily Living , Machine Learning , Humans , Monitoring, Ambulatory/methods , Monitoring, Ambulatory/instrumentation , Wearable Electronic Devices , Accelerometry/instrumentation , Accelerometry/methods , Monitoring, Physiologic/methods , Monitoring, Physiologic/instrumentation
14.
Curr Oncol ; 31(7): 3643-3656, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39057140

ABSTRACT

To help determine the unmet need for improved diagnostic tools to evaluate patients with nonspecific signs and/or symptoms (NSSS) and suspicion of cancer, we examined patient characteristics, diagnostic journey, and cancer incidence of patients with NSSS within The US Oncology Network (The Network), a secondary care community oncology setting. This retrospective, observational cohort study included patients aged ≥40 years with ≥1 NSSS in their problem list at their first visit within The Network (the index date) between 1 January 2016 and 31 December 2020. Patients were followed longitudinally with electronic health record data for initial cancer diagnosis, new noncancer diagnosis, death, end of study observation period, or 12 months, whichever occurred first. Of 103,984 patients eligible for inclusion, 96,722 presented with only 1 NSSS at index date; 6537/103,984 (6.3%) were diagnosed with 1 primary cancer within 12 months after the index date; 3825/6537 (58.5%) with hematologic malignancy, and 2712/6537 (41.5%) with solid tumor. Among patients diagnosed with cancer (n = 6774), the median time to cancer diagnosis after their first visit within The Network was 5.13 weeks. This study provides a real-world perspective on cancer incidence in patients with NSSS referred to a secondary care setting and highlights the unmet need for improved diagnostic tools to improve cancer outcomes.


Subject(s)
Neoplasms , Secondary Care , Humans , Retrospective Studies , Neoplasms/epidemiology , Female , Male , Middle Aged , Aged , United States/epidemiology , Adult , Aged, 80 and over
15.
Pharmacy (Basel) ; 12(3)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38921972

ABSTRACT

The ever-evolving landscape of digital health technology has dramatically enhanced patients' ability to manage their health through self-care effectively. These advancements have created various categories of self-care products, including medication management, health tracking, and wellness. There is no published research regarding integrating digital health into pharmacy self-care courses. This study aims to identify pertinent digital health devices and applications to incorporate into self-care course education. Digital health limitations, challenges incorporating digital health in self-care pharmacy education, and potential solutions are also reviewed. In conducting this research, many resources, including PubMed, APhA, ASHP, fda.gov, and digital.health, were reviewed in March 2024 to gather information on digital health devices and applications. To supplement this, targeted keyword searches were conducted on topics such as "digital health", "devices", "applications", "technology", and "self-care" across various online platforms. We identified digital health devices and applications suitable for self-care education across eight topics, as follows: screening, insomnia, reproductive disorders, eye disorders, home medical equipment, GI disorders, pediatrics, and respiratory disorders. Among these topics, wellness screening had the most digital health products available. For all other topics, at least three or more products were identified as relevant to self-care curriculum. By equipping students with digital health knowledge, they can effectively apply it in patient care throughout their rotations and future practice. Many digital health products, including telemedicine, electronic health records, mobile health applications, and wearable devices, are ideal for inclusion in pharmacy curriculum as future educational material. Future research is needed to develop the best strategies for incorporating relevant digital health into self-care education and defining the best student-learning strategies.

16.
Lancet HIV ; 11(7): e461-e469, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38848736

ABSTRACT

BACKGROUND: Treatment as prevention and pre-exposure prophylaxis (PrEP) are key strategies in the control of HIV/AIDS. We aimed to characterise the longitudinal effects of antiretroviral therapy (ART), followed by treatment as prevention and the addition of PrEP, on the HIV effective reproduction number (Re) in British Columbia, Canada. METHODS: This population-level programme evaluation used data from the Drug Treatment Program of the British Columbia Centre for Excellence in HIV/AIDS (Vancouver, British Columbia, Canada). We also used estimates of HIV incidence and prevalence from the Public Health Agency of Canada, data on the number of new HIV diagnoses per year from the British Columbia Centre for Disease Control, and mortality data from the British Columbia Vital Statistics Agency. Data were obtained from 1985 until 2022, depending on the database source. Outcomes were the annual HIV prevalence, HIV incidence, number of new HIV diagnoses, number of people living with HIV on ART, HIV/AIDS-related and all-cause mortality rates, the HIV incidence-to-all-cause-mortality ratio, and Re. We calculated the modified effective reproduction number (Rme) using two thresholds of viral suppression and compared these values with Re. FINDINGS: We found a 95% decline in HIV/AIDS-related mortality and a 91% decrease in HIV incidence over the study period. The Re progressively declined from 1996 to 2022; however, from 1996 to 2017, Rme remained stable (>1) when calculated for people living with HIV with unsuppressed viraemia, suggesting that treatment as prevention reduces HIV incidence by decreasing the pool of individuals who are potentially able to transmit the virus. From 2018 to 2022, a decline in the estimated Re and Rme (<1) was observed regardless of whether we considered all people living with HIV or only those who were virologically unsuppressed. This finding suggests that PrEP decreases HIV incidence by reducing the number of susceptible individuals in the community, independently of viral suppression. INTERPRETATION: Our results show the synergy between generalised treatment as prevention and targeted PrEP in terms of decreasing HIV incidence. These findings support the incorporation of longitudinal monitoring of Re at a programmatic level to identify opportunities for the optimisation of treatment-as-prevention and PrEP programmes. FUNDING: British Columbia Ministry of Health, Health Canada, Public Health Agency of Canada, Vancouver Coastal Health, Vancouver General Hospital Foundation, Genome British Columbia, and the Canadian Institutes of Health Research.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Program Evaluation , Humans , British Columbia/epidemiology , HIV Infections/drug therapy , HIV Infections/prevention & control , HIV Infections/epidemiology , Incidence , Male , Female , Prevalence , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Longitudinal Studies , Adult , Middle Aged , Basic Reproduction Number
17.
Front Public Health ; 12: 1381146, 2024.
Article in English | MEDLINE | ID: mdl-38903584

ABSTRACT

Background: Heart failure (HF) risk is greater in rural versus urban regions in the United States (US), potentially due to differences in healthcare coverage and access. Whether this excess risk applies to countries with universal healthcare is unclear and the underlying biological mechanisms are unknown. In the prospective United Kingdom (UK) Biobank, we investigated urban-rural regional differences in HF risk and the mechanistic role of biological aging. Methods: Multivariable Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to residential urban-rural region and a Biological Health Score (BHS) that reflects biological aging from environmental, social, or dietary stressors. We estimated the proportion of the total effect of urban-rural region on HF mediated through BHS. Results: Among 417,441 European participants, 10,332 incident HF cases were diagnosed during the follow-up. Compared to participants in large urban regions of Scotland, those in England/Wales had significantly increased HF risk (smaller urban: HR = 1.83, 95%CI: 1.64-2.03; suburban: HR = 1.77, 95%CI: 1.56-2.01; very rural: HR = 1.61, 95%CI: 1.39-1.85). Additionally, we found a dose-response relationship between increased biological aging and HF risk (HRper 1 SD increase = 1.14 (95%CI: 1.12-1.17). Increased biological aging mediated a notable 6.6% (p < 0.001) of the total effect of urban-rural region on HF. Conclusion: Despite universal healthcare in the UK, disparities in HF risk by region were observed and may be partly explained by environmental, social, or dietary factors related to biological aging. Our study contributes to precision public health by informing potential biological targets for intervention.


Subject(s)
Aging , Heart Failure , Rural Population , Humans , Heart Failure/epidemiology , United Kingdom/epidemiology , Female , Male , Middle Aged , Aged , Rural Population/statistics & numerical data , Prospective Studies , Risk Factors , Urban Population/statistics & numerical data , Proportional Hazards Models , Adult
18.
medRxiv ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38903105

ABSTRACT

Background: Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. Methods: We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190,613 men and 224,853 women with genotyping data from the UK Biobank. Among these participants, we analyzed 37,037 men with mLOY and 13,978 women with mLOX detected using Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization (MR) was conducted to estimate causal associations. Results: Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR=1.06, 95%CI:1.03-1.11). The associations were apparent in both never-smokers (HR=1.07, 95%:1.01-1.14) and ever-smokers (HR=1.05, 95%CI:1.01-1.11) as well as men > and ≤60 years of age. MR analyses supported causal associations between mLOY and atrial fibrillation (HRMR-PRESSO=1.15, 95%CI:1.13-1.18). Among post-menopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR=0.90, 95%CI:0.83-0.98). However, associations with mLOY and mLOX were not found for other heart diseases. Conclusions: Our findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.

19.
Vaccines (Basel) ; 12(5)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38793696

ABSTRACT

(1) Background: Vaccination reluctance is a major worldwide public health concern as it poses threats of disease outbreaks and strains on healthcare systems. While some studies have examined vaccine uptake within specific countries, few provide an overview of the barriers and trends among migrant groups. To fill this knowledge gap, this narrative review analyzes immunization patterns and vaccine hesitancy among immigrant populations. (2) Methods: Four researchers independently evaluated the quality and bias risk of the 18 identified articles using validated critical appraisal tools. (3) Results: Most studies focused on vaccine hesitancy among migrants in the United States and Canada, with a higher COVID-19 vaccine reluctance than native-born residents. Contributing factors to this hesitancy include demographics, cultural views, obstacles to healthcare access, financial hardship, and distrust in health policies. Additionally, immigrants in North America and Europe face unfair vaccine challenges due to misinformation, safety concerns, personal perspectives, language barriers, immigration status, and restricted healthcare access. (4) Conclusions: Tailored vaccine education programs and outreach campaigns sensitive to immigrants' diversity should be developed to address this issue. It is also important to investigate community-specific obstacles and assess the long-term sustainability of current efforts to promote vaccination among marginalized migrant groups. Further research into global immunization disparities among immigrant populations is crucial.

20.
Viruses ; 16(5)2024 04 23.
Article in English | MEDLINE | ID: mdl-38793537

ABSTRACT

We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval [CI] 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.


Subject(s)
Antiviral Agents , COVID-19 , Hepatitis C , Interrupted Time Series Analysis , Humans , British Columbia/epidemiology , COVID-19/epidemiology , Hepatitis C/epidemiology , Hepatitis C/drug therapy , Male , Female , Antiviral Agents/therapeutic use , Middle Aged , Adult , SARS-CoV-2 , Substance Abuse, Intravenous/epidemiology , Substance Abuse, Intravenous/complications , Pandemics , Aged , Cohort Studies
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