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Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder.
Get PDFIMPORTANCE: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.
OBJECTIVE: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study examined the association of 15 candidate genetic variants with risk of OUD using electronic health record data from December 20, 1992, to September 30, 2022. Electronic health record data, including pharmacy records, were accrued from participants in the Million Veteran Program across the US with opioid exposure (n = 452 664). Cases with OUD were identified using International Classification of Diseases, Ninth Revision, or International Classification of Diseases, Tenth Revision, diagnostic codes, and controls were individuals with no OUD diagnosis.
EXPOSURES: Number of risk alleles present across 15 candidate genetic variants.
MAIN OUTCOME AND MEASURES: Performance of 15 genetic variants for identifying OUD risk assessed via logistic regression and machine learning models.
RESULTS: A total of 452 664 individuals with opioid exposure (including 33 669 with OUD) had a mean (SD) age of 61.15 (13.37) years, and 90.46% were male; the sample was ancestrally diverse (with individuals of genetically inferred European, African, and admixed American ancestries). Using Nagelkerke R2, collectively, the 15 candidate genes accounted for 0.40% of variation in OUD risk. In comparison, age and sex alone accounted for 3.27% of the variation. The ensemble machine learning. The ensemble machine learning model using the 15 variants as predictive factors correctly classified 52.83% (95% CI, 52.07%-53.59%) of individuals in an independent testing sample.
CONCLUSIONS AND RELEVANCE: Results of this study suggest that the candidate genetic variants included in the approved algorithm do not meet reasonable standards of efficacy in identifying OUD risk. Given the algorithm's limited predictive accuracy, its use in clinical care would lead to high rates of both false-positive and false-negative findings. More clinically useful models are needed to identify individuals at risk of developing OUD
Understanding the role of metabolic syndrome in prostate cancer risk: A UK Biobank prospective cohort study.
Get PDFPredictive value of metabolic syndrome for prostate cancer risk is not clear. We aimed to assess the association between metabolic syndrome and its components with prostate cancer incidence. The primary outcome was prostate cancer incidence, i.e., incidence rate ratios and adjusted cumulative incidence curves derived from flexible parametric survival models. Adjusted cumulative incidence curves were derived using a flexible survival parametrical modeling framework. We analysed UK Biobank data including 242,349 adult males, recruited during 2006-2010 and followed up until 2021, during which 6,467 (2.7%) participants were diagnosed with prostate cancer. Our findings indicate that metabolic syndrome, as a whole, was not associated with prostate cancer risk (incidence rate ratios, 1.07; 95% confidence interval, 0.94-1.22). However, specific components such as hypertension and obesity increased the risk (incidence rate ratios, 1.22; 95% confidence interval, 1.03-1.44 and incidence rate ratios, 1.24; 95% confidence interval, 1.05-1.46, respectively). Other components, such as prediabetes/diabetes and low cholesterol, were associated with a reduced risk (incidence rate ratios, 0.80; 95% confidence interval, 0.67-0.94 and incidence rate ratios, 0.82; 95% confidence interval, 0.69-0.97, respectively), while hyperlipidaemia showed no significant effect (incidence rate ratios, 1.07; 95% confidence interval, 0.93-1.24). Further research is needed to understand the underlying mechanisms behind these relationships. Prostate cancer prevention strategies might benefit from targeting modifiable risk factors, particularly hypertension and obesity
The use of mobile phone surveys for rapid mortality monitoring: A national study in Burkina Faso
Get PDFBACKGROUND: In low- and middle-income countries, death registration remains low, and mortality estimation is heavily based on surveys and censuses conducted through face-to-face interviews. These operations are costly and time-consuming, and are difficult to conduct during health and security crises. Taking advantage of the rapid increase in cell phone network coverage, mobile phone surveys (MPS) have recently started to be used to collect mortality data.
OBJECTIVES: We computed mortality levels obtained from a national MPS conducted in 2021–2022 in Burkina Faso and compare them to estimates from censuses, surveys, and modeled estimates developed by United Nations agencies.
METHODS: The MPS included three modules adapted from standard questionnaires to reduce interview length: (1) truncated birth histories, (2) summary sibling histories, and (3) parental survival histories. We applied direct and indirect mortality estimation methods and used post-stratification weights to account for sample selectivity.
RESULTS: Indirect estimates of under-5 mortality aligned with UN estimates, but direct estimates extracted from truncated birth histories provided lower mortality rates. However, these lower direct estimates were consistent with the latest Demographic and Health Surveys, conducted in 2021. MPS estimates of 35q15 derived from the sibling histories were about half of those published by the UN. This downward bias is likely due to errors in reporting siblings’ ages and timing of death. Mortality levels at older ages (30q50) from the parental survival histories were also substantially lower than model-based UN estimates (with a relative difference of –20% among men and –34% among women).
CONTRIBUTION: MPS are a promising tool for the rapid measurement of age-specific mortality in settings where face-to-face surveys are difficult to implement. However, our findings also indicate that further research is needed to evaluate and improve on the quality of data collected over the phone
Reducing fragmentation of primary healthcare financing for more equitable, people-centred primary healthcare.
Get PDFDespite primary healthcare (PHC) being recognised in global declarations-Alma Ata in 1978 and Astana in 2018-and prioritised in national health strategies, chronic under-resourcing of PHC persists in most low-income and middle-income countries. More public spending is needed for PHC, but macrofiscal and political constraints often limit the ability of governments to allocate more public resources to PHC. Under-resourcing has been compounded by fragmented and rigid funding flows, which are inefficient and may erode equity, quality of care and public trust in PHC.This article explores the drivers of fragmentation in PHC financing-low public spending, which results in over-reliance on external sources to fund critical health interventions, and the proliferation of new financing schemes that do not take a system-wide view or adhere to the principles of universality. It then highlights some of the possible consequences of this fragmentation for the efficiency, equity and effectiveness of service delivery.Four countries-Argentina, Burkina Faso, Indonesia and Tanzania-are used to illustrate practical steps that may be taken to minimise the consequences of fragmentation in PHC financing: (1) consolidating multiple coverage schemes, (2) avoiding further fragmentation, (3) harmonising health purchasing functions and (4) streamlining funding flows to the provider level.The country examples reveal lessons for policy-makers grappling with the consequences of fragmented PHC financing. The paper concludes with a research agenda to generate additional evidence on what works to address fragmentation
Water quality and hydrologic connectivity in rural communities around the Manombo Special Reserve of southeastern Madagascar during the dry season
Get PDFThis study establishes a cross-sectional understanding of the water quality and hydrologic connectivity during the dry season among rural communities near the Manombo Special Reserve along the coast of the Atsimo-Atsinanana region of southeastern Madagascar, a region impacted by diarrheal disease, tropical cyclones, and flooding. Conducting one measurement per site during the dry season, we collected surface and well water samples from eleven rural villages outside the Manombo Special Reserve and surface water samples from nine locations within the Manombo Special Reserve and tested for inorganic and bacteriological contamination. Earth observation data was utilized to map the watershed, stream order, and connectivity between water sample sources in the study area. We found negligible inorganic contamination in all of the villages and areas of the Manombo Special Reserve. However, the majority of villages contained levels of total coliforms and Escherichia coli (E. coli) exceeding the World Health Organization standards and the Malagasy Potability Standards for drinking water. Village water sources were categorized into two types of use, drinking-only and general-use (e.g., for washing and bathing). There was a significant difference in E. coli concentrations between drinking-only and general-use sources. We did not find a substantial difference between E. coli levels in the Manombo Special Reserve and the villages. The watershed delineation revealed that the majority of the water sources were first-order ephemeral streams, and some of the drinking-only sources were located downstream from contaminated general-use sources. Investigation into E. coli strains and sources, seasonal variability and temporal trends, hydrologic dynamics, and climate-related events is required to understand the drivers of bacteriological contamination and associated health outcomes
Potential role of proprietary patent medicine vendors in primary eye and ear care: A mixed methods study in northern Nigeria.
Get PDFBACKGROUND: In Nigeria, patent and proprietary medicine vendors (PPMVs) are permitted to sell a limited range of medication. They are important providers of health care despite their limitations and may be trained to manage specific conditions, such as malaria, but not ear and eye conditions. In this study, PPMV's knowledge and management of ear and eye problems and community members health seeking behaviour were explored, as well as whether community members would access PPMVs if they were trained in primary ear and eye care. METHODS: Quantitative and qualitative methods were used in a cross-sectional observation study: a survey of 1,591 adults in 40 clusters in two urban and two rural areas; 64 focus group discussions with community members and four with health professionals in two ear, nose, throat and eye clinics; in-depth interviews with ten community leaders, 11 primary health care workers, and 21 hospital staff. A check list was used to assess 36 PPMVs' facilities and structured questionnaires were administered to 36 PPMVs and 401 hospital patients in ear and eye outpatient departments. RESULTS: Community members reported that eye and ear problems were frequent but less common than other conditions. Health seeking behaviour was influenced by accessibility, availability, cost of medication, and trust in the provider. Most PPMVs had no formal training, had little knowledge of ear and eye conditions and were enthusiastic about being trained to manage them. Living far (>5km) from a health facility, being male, uneducated and poor were significantly associated with willingness to access PPMV after training in primary ear or eye care. CONCLUSIONS: PPMVs might be able to play a role in delivering primary ear and eye health care for common conditions, in collaboration with local clinicians. To do this, PPMVs would require training in eye and ear conditions and skills in their detection and counselling clients as well as reliable supply chains for medication, and skills in stock control, record keeping and facility management
Is differential cleaning needed for SARS-CoV-2 beyond standard procedures? A systematic review.
Get PDFBACKGROUND: There is a substantial risk of indirect transmission of SARS-CoV-2 from contaminated surfaces and objects in healthcare settings.
AIM: To evaluate the effectiveness of enhanced cleaning protocols for high-touch surfaces during COVID-19, focusing on cleaning products, concentrations, contact time, and recommended frequency.
SETTING: We focused on research conducted in healthcare settings or where samples were obtained from healthcare environments.
METHOD: We assessed studies that compared different cleaning, disinfection, sterilisation, or decontamination procedures and cleaning frequency with standard or routine procedures. We prioritised randomised trials, non-randomised controlled trials, controlled before-and-after studies, and interrupted time series analyses carried out between 01 January 2020 and 31 August 2022.
RESULTS: Three studies met our criteria from 2139 references searched. These studies, which took place in Iran, China and the United States, found that routine terminal cleaning and enhanced terminal cleaning with different cleaning enhancements significantly reduced SARS-CoV-2 surface contamination. One of the studies tested residual SARS-CoV-2 levels after routine and terminal cleaning with varying strengths of disinfectant and evaluated the efficacy of two common types of disinfectants in inactivating SARS-CoV-2 on inanimate surfaces in different hospital wards.
CONCLUSION: Limited evidence supports cleaning strategies that can reduce the transmission of SARS-CoV-2 from surfaces in healthcare settings. Combining various cleaning methods and using multiple disinfectants can effectively reduce surface contamination.
CONTRIBUTION: Randomised controlled trials are crucial for evaluating cleaning effectiveness. They must outline cleaning protocols, detailing frequency, product concentration and volume, application methods, soil and surface types, and environmental conditions, to provide strong evidence
Investigation of severe dengue outbreak in Maumere, East Nusa Tenggara, Indonesia: Clinical, serological, and virological features.
Get PDFBACKGROUND: Dengue, an acute febrile disease caused by dengue virus (DENV) infection, is endemic to Indonesia. During early 2020, an outbreak of severe dengue occurred in Maumere, East Nusa Tenggara province, a region with low dengue endemicity with limited data on the characteristics of the circulating DENV. By 18 March 2020, 1396 cases were reported with 14 fatalities. Investigation was conducted to understand the cause and characteristics of the outbreak. METHODS: Sera were collected from 133 patients with dengue-like symptoms through random sampling at TC Hillers Hospital, Maumere during outbreak between February and June 2020. Dengue was confirmed using NS1 and/or RT-PCR detection. Serological status was determined using IgG/IgM ELISA and plaque reduction neutralization test (PRNT). DENV serotyping and genome sequencing were performed to identify the DENV serotype and genotype. RESULTS: We recruited suspected dengue patients attending the hospital during the outbreak. Dengue was confirmed in 72.2% (96/133), while 18.8% (25/133) were diagnosed as probable dengue. Children under 18 years old accounted for 85.1% (103/121) of dengue cases. Severe dengue accounted for 94.2% (81/86) of cases. Secondary infections made up 92.6% (112/121) of cases. Serotyping detected 87.3% (62/71) as DENV-3, 7.0% (5/71) as DENV-4, 2.8% (2/71) as DENV-1, and 2.8% (2/71) as DENV-2. Phylogenetic analysis revealed close evolutionary relationship of Maumere DENV to viruses from other Indonesian regions, especially Bali and Kupang. PRNT on DENV-3 secondary infections patients detected the presence of DENV-2 and DENV-4 neutralizing antibodies. CONCLUSION: The severe dengue outbreak in Maumere is caused by DENV-3 introduced from nearby islands. The high proportion of secondary infections likely contributes to the severity of the disease. The high percentage of anti-dengue neutralizing antibodies for multiple serotypes and the high proportion of anti-dengue IgG in young children suggests a history of dengue transmission with a high infection rate in the area
Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset.
Get PDFOBJECTIVE: Epigenetic DNA imprints are increasingly being recognized as co-drivers of disease in complex conditions. In this exploratory and hypothesis-generating epigenome-wide association study (EWAS), we investigated differential methylation patterns in peripheral blood leucocytes from patients with early untreated ACPA-positive rheumatoid arthritis (RA) versus controls. METHODS: Whole blood DNA was isolated from 101 disease-modifying anti-rheumatic drug (DMARD)-naïve patients with recent clinical onset of ACPA-positive RA and 200 controls. DNA methylation was studied using the Illumina MethylationEPIC BeadChips (Illumina). We assessed our findings against previously reported differentially methylated DNA positions associated with RA including an EWAS on peripheral blood leucocytes from a similar Drop Nordic cohort. RESULTS: We identified 16,583 CpG sites and 14 differentially methylated regions (DMRs) associated with RA. The most robust DMRs were in the gene body of LAMP1 and the TNSF14 GENE known as LIGHT. We identified three novel Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the taste transduction pathway, the olfactory pathway, and the viral carcinogenesis pathway, which have not previously been associated with RA. We replicated 2,248 CpG sites reported earlier in an EWAS on peripheral blood leukocytes from RA patients of Scandinavian ancestry with incipient untreated ACPA-positive disease. CONCLUSION: We have detected a considerable number of epigenetic marks with potential relevance to the pathogenesis of RA. These findings may pave the way for the development of narrowly targeted new drugs and possibly assist to retrieve persons at particular risk of acquiring RA
Economic burden of myasthenia gravis in China: a nationwide registry-based study.
Get PDFBACKGROUND: The long-term treatment of myasthenia gravis (MG) and impaired productivity related to physical decline incur significant economic burdens on affected populations and society. This study aims to evaluate the costs of MG in China from a societal perspective and to identify the cost-driving factors. METHODS: A web-based survey was conducted on 1020 MG patients recruited through a national registry system in China. Respondents reported their socio-demographic and disease-related information and annual expenses related to MG under direct medical and non-medical costs. Indirect costs were estimated among 268 working respondents based on hours of missed work and their annual income. Generalized linear models were used to identify factors associated with different categories of costs. RESULTS: Among all respondents, the median annual direct medical cost was US1860.2 contributed by medical costs and a median of $248.2 by non-medical costs. Higher education, unemployment, hospitalization, use of mechanical ventilation, and use of multiple medications were significant driving factors of direct medical and non-medical costs. Among respondents who are at least part-time employed, the indirect costs were generally minimal. Older age, physical burden of disease, and use of multiple medications were significant predictors of higher income loss. CONCLUSION: Population with MG in China reported heavy economic burdens related to medication. Disease severity is a major driving factor of both direct and indirect costs. Targeted policies are needed to alleviate the financial burden of MG on patients and society at large