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BackgroundVisual impairment has been strongly associated with the incidence of dementia. Appropriate cognitive screening for the elderly with visual impairment is crucial for early identification of dementia and its management. Due to challenges in processing visually presented stimuli among participants, the cut-off score of the Hong Kong version of the Montreal Cognitive Assessment for the Visually Impaired (HKMoCA-VI), also known as MoCA-BLIND or MoCA-22, was unknown. Besides, the cognitive status of elderly with visual impairment residing in care homes is rarely investigated. The current study aimed to 1) establish the cut-off score for HKMoCA-VI and 2) examine the general cognitive functioning of elderly with visual impairment living in residential homes in Hong Kong in terms of MoCA-VI percentile scores.MethodHKMoCA-VI and the Cantonese version of the Mini-Mental State Examination (CMMSE) were administered to 123 visually impaired elderly residents in care homes in Hong Kong. Percentile scores of HKMoCA-VI by age and education level were determined, and the concurrent validity, sensitivity, and specificity of HKMoCA-VI were assessed.ResultsA cut-off score 12 was suggested for HKMoCA-VI, which yielded a sensitivity and specificity of 89.29% and 83.58%, respectively. Moreover, it strongly correlated with CMMSE, indicating satisfactory concurrent validity.ConclusionsHKMoCA-VI is suggested to be a viable cognitive screening tool for elderly individuals with visual impairment in residential homes. Further modifications to enhance the sensitivity and specificity of the measure are proposed.

Heterogeneity in Sjögren’s syndrome (SS), increasingly called Sjögren’s disease, suggests the presence of disease subtypes, which poses a major challenge for the diagnosis, management, and treatment of this autoimmune disorder. Previous work distinguished patient subgroups based on clinical symptoms, but it is not clear to what extent symptoms reflect underlying pathobiology. The purpose of this study was to discover clinical meaningful subtypes of SS based on genome-wide DNA methylation data. We performed a cluster analysis of genome-wide DNA methylation data from labial salivary gland (LSG) tissue collected from 64 SS cases and 67 non-cases. Specifically, hierarchical clustering was performed on low dimensional embeddings of DNA methylation data extracted from a variational autoencoder to uncover unknown heterogeneity. Clustering revealed clinically severe and mild subgroups of SS. Differential methylation analysis revealed that hypomethylation at the MHC and hypermethylation at other genome regions characterize the epigenetic differences between these SS subgroups. Epigenetic profiling of LSGs in SS yields new insights into mechanisms underlying disease heterogeneity. The methylation patterns at differentially methylated CpGs are different in SS subgroups and support the role of epigenetic contributions to the heterogeneity in SS. Biomarker data derived from epigenetic profiling could be explored in future iterations of the classification criteria for defining SS subgroups.

[This corrects the article DOI: 10.1371/journal.pone.0248429.].

Differential methylation of immune genes has been a consistent theme observed in Sjögren's syndrome (SS) in CD4+ T cells, CD19+ B cells, whole blood, and labial salivary glands (LSGs). Multiple studies have found associations supporting genetic control of DNA methylation in SS, which in the absence of reverse causation, has positive implications for the potential of epigenetic therapy. However, a formal study of the causal relationship between genetic variation, DNA methylation, and disease status is lacking. We performed a causal mediation analysis of DNA methylation as a mediator of nearby genetic association with SS using LSGs and genotype data collected from 131 female members of the Sjögren's International Collaborative Clinical Alliance registry, comprising of 64 SS cases and 67 non-cases. Bumphunter was used to first identify differentially-methylated regions (DMRs), then the causal inference test (CIT) was applied to identify DMRs mediating the association of nearby methylation quantitative trait loci (MeQTL) with SS. Bumphunter discovered 215 DMRs, with the majority located in the major histocompatibility complex (MHC) on chromosome 6p21.3. Consistent with previous findings, regions hypomethylated in SS cases were enriched for gene sets associated with immune processes. Using the CIT, we observed a total of 19 DMR-MeQTL pairs that exhibited strong evidence for a causal mediation relationship. Close to half of these DMRs reside in the MHC and their corresponding meQTLs are in the region spanning the HLA-DQA1, HLA-DQB1, and HLA-DQA2 loci. The risk of SS conferred by these corresponding MeQTLs in the MHC was further substantiated by previous genome-wide association study results, with modest evidence for independent effects. By validating the presence of causal mediation, our findings suggest both genetic and epigenetic factors contribute to disease susceptibility, and inform the development of targeted epigenetic modification as a therapeutic approach for SS.

Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles.

Background: Visual impairment has been strongly associated with the incidence of dementia. Appropriate cognitive screening for the elderly with visual impairment is crucial for early identification of dementia and its management. Due to challenges in processing visually presented stimuli among participants, the cut-off score of the Hong Kong version of the Montreal Cognitive Assessment for the Visually Impaired (HKMoCA-VI), also known as MoCA-BLIND or MoCA-22, was unknown. Besides, the cognitive status of elderly with visual impairment residing in care homes is rarely investigated. The current study aimed to 1) establish the cut-off score for HKMoCA-VI and 2) examine the general cognitive functioning of elderly with visual impairment living in residential homes in Hong Kong in terms of MoCA-VI percentile scores. Method: HKMoCA-VI and the Cantonese version of the Mini-Mental State Examination (CMMSE) were administered to 123 visually impaired elderly residents in care homes in Hong Kong. Percentile scores of HKMoCA-VI by age and education level were determined, and the concurrent validity, sensitivity, and specificity of HKMoCA-VI were assessed. Results: A cut-off score 12 was suggested for HKMoCA-VI, which yielded a sensitivity and specificity of 89.29% and 83.58%, respectively. Moreover, it strongly correlated with CMMSE, indicating satisfactory concurrent validity. Conclusions: HKMoCA-VI is suggested to be a viable cognitive screening tool for elderly individuals with visual impairment in residential homes. Further modifications to enhance the sensitivity and specificity of the measure are proposed. [ABSTRACT FROM AUTHOR]

Abstract We investigate the functionality of NbOx-based selector devices on a flexible substrate. It was observed that the failure mechanism of cyclic tensile strain is from the disruption of atom arrangements, which essentially led to the crack formation of the film. When under cyclic compressive strain, buckling delamination of the film occurs as the compressed films have debonded from their neighboring layers. By implementing an annealing process after the strain-induced degradation, recovery of the device is observed with reduced threshold and hold voltages. The physical mechanism of the device is investigated through Poole–Frenkel mechanism fitting, which provides insights into the switching behavior after mechanical strain and annealing process. The result demonstrates the potential of the NbOx device in flexible electronics applications with a high endurance of up to 105 cycles of cyclic bending strain and the recovery of the device after degradation.

BackgroundSocial determinants of health (SDOH) such as lack of basic resources, housing, transportation, and social isolation play an important role for patients on the cancer care continuum. Health systems’ current technological solutions for identifying and managing patients’ SDOH data largely focus on information recorded in the electronic health record by providers, which is often inaccessible to patients to contribute to or modify. ObjectiveWe developed and tested a patient-centric SDOH screening tool designed for use on patients’ personal mobile phone that preserves patient privacy and confidentiality, collects information about the unmet social needs of patients with cancer, and communicates them to the provider. MethodsWe interviewed 22 patients with cancer, oncologists, and social workers associated with a US-based comprehensive cancer center to better understand how patients’ SDOH information is collected and reported. After triangulating data obtained from thematic analysis of interviews, an environmental scan, and a literature search of validated tools to collect SDOH data, we developed an SDOH screening tool mobile app and conducted a pilot study of 16 dyadic pairs of patients and cancer care team members at the same cancer center. We collected patient SDOH data using 36 survey items covering 7 SDOH domains and used validated scales and follow-up interviews to assess the app’s usability and acceptability among patients and cancer care team members. ResultsFormative interviews with patients and care team members revealed that transportation, financial challenges, food insecurity, and low health literacy were common SDOH challenges and that a mobile app that collected those data, shared those data with care team members, and offered supportive resources could be useful and valuable. In the pilot study, 25% (4/16) of app-using patients reported having at least one of the abovementioned social needs; the most common social need was social isolation (7/16, 44%). Patients rated the mobile app as easy to use, accurately capturing their SDOH, and preserving their privacy but suggested that the app could be more helpful by connecting patients to actual resources. Providers reported high acceptability and usability of the app. ConclusionsUse of a brief, patient-centric, mobile app–based SDOH screening tool can effectively capture SDOH of patients with cancer for care team members in a way that preserves patient privacy and that is acceptable and usable for patients and care team members. However, only collecting SDOH information is not sufficient; usefulness can be increased by connecting patients directly to resources to address their unmet social needs.

In this study, we examined the clinical and electrophysiological outcomes of adolescents in Hong Kong who developed myocarditis or pericarditis following BNT162b2 vaccination for COVID-19, and followed-up for 60–180 days after their initial diagnosis. Clinical assessments included electrocardiogram (ECG) and echocardiogram at the initial admission and follow-up were compared. Treadmill testing was also performed in some cases. Between 14 June 2021 and 16 February 2022, 53 subjects were approached to participate in this follow-up study, of which 28 patients were followed up for >60 days with a median follow-up period of 100 days (range, 61–178 days) and were included in this study. On admission, 23 patients had ECG abnormalities but no high-grade atrioventricular block. Six patients had echocardiogram abnormalities, including reduced contractility, small rim pericardial effusions, and hyperechoic ventricular walls. All patients achieved complete recovery on follow-up. After discharge, 10 patients (35.7%) reported symptoms, including occasional chest pain, shortness of breath, reduced exercise tolerance, and recurrent vasovagal near-syncope. At follow-up, assessments, including ECGs, were almost all normal. Among the three patients with possible ECG abnormalities, all their echocardiograms or treadmill testings were normal. Sixteen patients (57.1%) underwent treadmill testing at a median of 117 days post-admission, which were also normal. However, at follow-up, there was a significant mean bodyweight increase of 1.81 kg (95%CI 0.47-3.1 kg, p = 0.01), possibly due to exercise restriction. In conclusion, most adolescents experiencing myocarditis and pericarditis following BNT162b2 vaccination achieved complete recovery. Some patients developed non-specific persistent symptoms, and bodyweight changes shall be monitored.

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of

Objectives To examine how sales of sexual and reproductive health (SRH) products varied among pharmacies in Kenya using administrative data, leveraging natural variation in the COVID-19 pandemic and accompanying policy restrictions between 2019 and 2021.Design and setting Ecological study of pharmacies in Kenya.Participants 761 pharmacies using the Maisha Meds product inventory management system (capturing 572 916 products sold).Outcomes Sales quantity, price and revenue of SRH products sold per pharmacy per week.Results COVID-19 deaths were associated with a −2.97% (95% CI −3.82%, −2.11%) decrease in sales quantity, a 1.09% (95% CI 0.44%, 1.72%) increase in sales price and a −1.89% (−1.00%, −2.79%) decrease in revenues per pharmacy per week. Results were similar when considering new COVID-19 cases (per 1000) and the Average Policy Stringency Index. Results differed substantially between individual SRH products—a large decrease in sales quantity in pregnancy tests, injectables and emergency contraception, a modest decrease in condoms and no change in oral contraception. Sales price increases were similarly varied; four of the five most sold products were revenue neutral.Conclusions We found a robust negative association between SRH sales at pharmacies in Kenya and COVID-19 reported cases, deaths and policy restriction. Although our data cannot definitively point to reduced access, existing evidence from Kenya regarding unchanged fertility intentions, increases in unintended pregnancies and reported reasons for non-use of contraceptives during COVID-19 suggests a prominent role of reduced access. While policymakers may have a role in sustaining access, their role may be limited by broader macroeconomic problems, such as global supply chain disruptions and inflation, during supply shocks.

Introduction Though community health workers (CHWs) have improved access to antenatal care (ANC) and institutional delivery in different settings, it is unclear what package and delivery strategy maximises impact.Methods This study reports a secondary aim of the Proactive Community Case Management cluster randomised trial, conducted between December 2016 and April 2020 in Mali. It evaluated whether proactive home visits can improve ANC access at a population level compared with passive site-based care. 137 unique village clusters, covering the entire study area, were stratified by health catchment area and distance to the nearest primary health centre. Within each stratum, clusters were randomly assigned to intervention or control arm. CHWs in intervention clusters proactively visited all homes to provide care. In the control clusters, CHWs provided the same services at their fixed community health post to care-seeking patients. Pregnant women 15–49 years old were enrolled in a series of community-based and facility-based visits. We analysed individual-level annual survey data from baseline and 24-month and 36-month follow-up for the secondary outcomes of ANC and institutional delivery, complemented with CHW monitoring data during the trial period. We compared outcomes between: (1) the intervention and control arms, and (2) the intervention period and baseline.Results With 2576 and 2536 pregnancies from 66 and 65 clusters in the intervention and control arms, respectively, the estimated risk ratios for receiving any ANC was 1.05 (95% CI 1.02 to 1.07), four or more ANC visits was 1.25 (95% CI 1.08 to 1.43) and ANC initiated in the first trimester was 1.11 (95% CI 1.02 to 1.19), relative to the controls; no differences in institutional delivery were found. However, both arms achieved large improvements in institutional delivery, compared with baseline. Monitoring data show that 19% and 2% of registered pregnancies received at least eight ANC contacts in the intervention and control arms, respectively. Six clusters, three from each arm had to be dropped in the last 2 years of the trial.Conclusions Proactive home visits increased ANC and the number of antenatal contacts at the clinic and community levels. ANC and institutional delivery can be increased when provided without fees from professional CHWs in upgraded primary care clinics.Trial registration number NCT02694055.

Abstract The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care. Trial Registration ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936.

Abstract Background First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. Methods In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). Results Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89–0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. Conclusions EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure–function analysis.

Abstract Background Public health initiatives must look for ways to cost-effectively scale critical interventions to achieve high coverage. Private sector distribution channels, can potentially distribute preventive healthcare products to hard-to-reach populations, decongest public healthcare systems, and increase the sustainability of programs by getting customers to share costs. However, little is known about how sellers set prices for new products. By introducing a new product, HIV self-test kits, to local drug shops, we observed whether shops experimented with pricing, charged different buyers different prices, and whether prices converged within the local market over our study period. Methods From August to December 2019, we provided free HIV self-test kits, a new product, to 26 drug shops in Shinyanga, Tanzania to sell to the local community. We measured sales volume, price, customer age and sex using shop records. Using a multiple linear regression model, we conducted F-tests to determine whether shop, age, sex, and time (week) respectively were associated with price. We measured willingness-to-pay to restock test kits at the end of the study. Results 514 test kits were sold over 18 weeks; 69% of buyers were male, 40% were aged 25–34 and 32% aged 35–44. Purchase prices ranged from 1000 to 6000 Tsh (median 3000 Tsh; ~$1.30 USD). Within shops, prices were 11.3% higher for 25–34 and 12.7% higher for 45+ year olds relative to 15–19-year olds (p = 0.029) and 13.5% lower for men (p = 0.023) on average. Although prices varied between shops, prices varied little within shops over time, and did not converge over the study period or cluster geospatially. Mean maximum willingness-to-pay to restock was 2000 Tsh per kit. Conclusions Shopkeepers charged buyers different prices depending on buyers’ age and sex. There was limited variation in prices within shops over time and low demand among shopkeepers to restock at the end of the study. Given the subsidized global wholesale price ($2 USD or ~ 4600 Tsh), further demand creation and/or cost-reduction is required before HIV self-test kits can become commercially viable in drug shops in this setting. Careful consideration is needed to align the motivations of retailers with public health priorities while meeting their private for-profit needs.

ABSTRACTAs another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p