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Development of the Advised Protocol for OCT Study Terminology and Elements Anterior Segment OCT extension reporting guidelines: APOSTEL-AS

mer, 22/11/2023 - 00:00
Background: Anterior segment optical coherence tomography (AS-OCT) is emerging as a valuable diagnostic, monitoring and predictive tool across a range of disorders. Clinical utility of quantitative information derived from AS-OCT has been suggested for ophthalmic disorders such as glaucoma, corneal disease and uveitis, which taken together comprise the majority of the blinding conditions affecting working age individuals. The current absence of guidelines for reporting OCT studies which quantitatively assess the anterior segment is an obstacle to reproducibility and interoperability. In order to provide this guidance, we aim to extend the existing Advised Protocol for OCT Study Terminology and Elements (APOSTEL) guidelines, to enable inclusion of items applicable to AS-OCT. Methods The guideline will be developed through a staged consensus process involving literature review and Delphi consensus exercise across an international multi-disciplinary stakeholder committee. A systematic scoping review will be used to generate candidate items for the guideline extension, and to form the expert membership base (eye healthcare professionals, patients, methodologists, statisticians, computer scientists, industry representatives, health informaticists, and journal editors) of the consensus group. The candidate reporting items will be presented to consensus group members, alongside the existing APOSTEL items, in a Delphi consensus exercise. Members will be asked to vote on each item using a 9-point scale, and to provide explanatory notes. Aggregated responses will be presented at the second Delphi round, and anonymous electronic voting will be used to include or exclude existing, reworded or amended, or newly suggested items. Items achieving consensus (>80%) will be included. Any item not achieving consensus but which is approved by the majority (51-80% inclusive) will be considered for further amendment or refinement and representation in a subsequent round. The resultant APOSTEL-AS guideline will undergo piloting, with feedback from this pilot used to produce the final version. Discussion AS-OCT is increasingly being used to derive quantitative data from images of normal physiology and for disease involving the anterior segment of the eye. Through APOSTEL-AS, we seek to provide timely support for researchers to ensure future standardisation, interoperability and reproducibility of reported work.
Catégories: Actus Santé

The role of systemic therapies in current and emerging opportunities for de-intensification in melanoma: a scoping review protocol

mer, 22/11/2023 - 00:00
Objective The purpose of this scoping review is to identify the role of systemic therapies in current and emerging opportunities to de-intensify systemic treatment of cutaneous melanoma. It will also seek to comment on the proportion of studies that include patient-reported outcomes and quality of life measures. Introduction With healthcare costs rising, focus is shifting towards maximising health outcomes per dollar. One approach to optimising value is through de-intensification, which is the rationalisation of routine treatment without compromising patient outcomes. Since 2013, successful clinical trials of high-cost immune checkpoint, BRAF and MEK inhibition have led to these drugs becoming ubiquitous in melanoma management. Pipeline therapies such as relatlimab and Tumour Infiltrating Lymphocyte (TIL) therapy are expected to have a similar or even greater cost. We hypothesize that neoadjuvant and response-directed strategies will be identified as well as the emerging potential of prognostic and predictive tools. Inclusion criteria This review aims to include studies of adult patients with cutaneous melanoma that report on de-escalation or de-intensification of internationally accepted standard-of-care systemic therapies or the use of systemic therapies to de-intensify subsequent surgery or radiotherapy. Systemic treatment across any stage of disease will be considered. A full-text English-language version must be available for a study to be eligible. Methods A systematic search strategy has been developed for MEDLINE, EMBASE and PubMed from 1 January 2013 to 30 June 2023. Additional texts will be sourced from grey literature, Google Scholar and reference scanning. Two authors will screen abstracts and full texts facilitated by the Covidence software. Disagreements will be resolved by consensus or a third reviewer. The first author (JS) will perform data extraction whilst a second author (FF) will review a random selection of papers to ensure consistent interpretation. De-intensification strategies will be categorised by concept, potential impact on resource utilisation and patient outcomes, and strength of evidence. Data will be synthesised qualitatively and quantitatively. Results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The results of this scoping review will directly inform a melanoma consumer and clinician survey exploring their perspectives on de-intensification strategies.
Catégories: Actus Santé

Job Demands, Social Support, and Burnout among Public Senior High School Teachers, Ghana

mer, 22/11/2023 - 00:00
This study aimed to investigate the extent to which job demands and social support predict burnout of public senior high school (S.H.S.) teachers in Ghana, and to determine the mediating effect of job resources in the relation between job demands and burnout among these teachers. Employing a quantitative survey, 1028 public S.H.S. teachers were selected using purposive and voluntary sampling methods. A questionnaire adopted from pre-existing standardized instruments yielded composite reliability between 0.94 and 0.98. Data was analyzed using mean, standard deviation, and multiple linear regression. Results revealed a high level of job demands (M = 3.23, SD = 0.43), social support (M = 3.02, SD = 0.54), and burnout (M = 3.33, SD = 0.92) among the teachers. Also, multiple linear regression results indicate that job demands, and social support predict burnout of the teachers. Furthermore, social support is a partial mediator of the effect of job demands on teachers burnout. Therefore, perceived high level of burnout is an effect of high levels of job demands, which poses a serious threat to the health and well-being of these teachers and compromises teaching quality in Ghanas S.H.S. However, this challenge can be prevented or reduced by providing more social support to the teachers. Hence, government, management, and other educational stakeholders need to provide a strong safety leadership in all matters that concerns teachers health and safety. The school administrators and teachers are also encouraged to promote social support vertically and horizontally.
Catégories: Actus Santé

Exogenous ketosis attenuates acute mountain sickness and mitigates high-altitude hypoxemia

mer, 22/11/2023 - 00:00
Background: Acute mountain sickness (AMS) represents a considerable issue for individuals sojourning to high altitudes with systemic hypoxemia known to be intimately involved in its development. Based on recent evidence that ketone ester (KE) intake attenuates hypoxemia, we sought to investigate whether exogenous ketosis might mitigate AMS development and improve hypoxic tolerance. Methods: Fourteen healthy, male participants were enrolled in two 29h protocols (simulated altitude of 4,000-4,500m) receiving either KE or a placebo (CON) at regular timepoints throughout the protocol in a randomized, crossover manner. Select physiological responses were characterized after 15min and 4h in hypoxia, and the protocol was terminated prematurely upon development of severe AMS. Results: All participants tolerated the protocol equally long (n=6, of which n=5 completed the protocol in both conditions) or longer (n=8) in KE. Overall protocol duration increased by 32% on average with KE, and doubled for AMS-developing participants. KE consistently induced diurnal ketosis, a mild metabolic acidosis, hyperventilation, and relative sympathetic dominance. KE also fully negated the progressive hypoxemia that was observed between 15min and 4h in hypoxia in CON, while concomitantly increasing cerebral oxygenation and capillary pO2 within this timeframe. This coincided with a KE-induced reduction in cerebral oxygen supply, suggesting that KE reduced cerebral oxygen consumption under hypoxic conditions. Conclusions: These data indicate that exogenous ketosis improves hypoxic tolerance in humans and attenuates AMS development. The key underlying mechanisms include improved arterial and cerebral oxygenation, in combination with lowered cerebral blood flow and oxygen demand, and increased sympathetic dominance.
Catégories: Actus Santé

Exploring the possibility of collaboration for biomedical professionals and traditional healers: A Systematic Review

mer, 22/11/2023 - 00:00
Introduction: Traditional healers play a crucial role in healthcare provision, particularly in low- and middle-income countries. Thus, there is a global interest in understanding the possibilities for collaboration between traditional healers and biomedical professionals. We believe there is the need for a comprehensive review on collaboration between traditional healers and biomedical professionals. Therefore, the aim of this review is to synthesise the literature on collaboration between traditional healers and biomedical professional including relevant interventions. Methods: A systematic review was conducted, utilizing a search strategy in PubMed, Web of Science, SCOPUS, and Google Scholar. Articles addressing collaboration between traditional healers and biomedical professionals were included, with a focus on attitudes, perceptions, interventions, and collaborative models. Data extraction followed a predefined template and the D'Amour et al. framework was employed for analysis. Results: The review identified 29 relevant articles, predominantly conducted in Africa. The majority of studies (n=22) explored attitudes and perceptions, revealing a willingness among traditional healers to collaborate, while biomedical professionals exhibited mixed feelings. Seven studies focused on interventions aimed at fostering collaboration primarily focused on improving referral systems and educational initiatives. These studies found positive outcomes. Examining collaboration through the lens of D'Amour et al.'s framework revealed that trust was a significant barrier to collaboration. Conclusion: This review highlights a willingness to collaborate amongst of traditional healers and biomedical professionals and provides some successful examples of working across systems. It also reveals areas for attention in developing collaborative models of working.
Catégories: Actus Santé

Global malaria predictors at a localized scale

mer, 22/11/2023 - 00:00
Malaria is a life-threatening disease caused by Plasmodium parasites transmitted by Anopheles mosquitoes. In 2021, more than 247 million cases of malaria were reported worldwide, with an estimated 619,000 deaths. While malaria incidence has decreased globally in recent decades, some public health gains have plateaued, and many endemic hotspots still face high transmission rates. Understanding local drivers of malaria transmission is crucial but challenging due to the complex interactions between climate, entomological and human variables, and land use. This study focuses on highly climatically suitable and endemic areas in Cote d'Ivoire to assess the explanatory power of coarse climatic predictors of malaria transmission at a fine scale. Using data from 40 villages participating in a randomized controlled trial of a household malaria intervention, the study examines the effects of climate variation over time on malaria transmission. Through panel regressions and statistical modeling, the study investigates which variable (temperature, precipitation, or entomological inoculation rate) and its form (linear or unimodal) best explains seasonal malaria transmission and the factors predicting spatial variation in transmission. The results highlight the importance of temperature and rainfall, with quadratic temperature and all precipitation models performing well, but the causal influence of each driver remains unclear due to their strong correlation. Further, an independent, mechanistic temperature-dependent R0 model based on laboratory data aligns well with observed malaria incidence rates, emphasizing the significance and predictability of temperature suitability across scales. By contrast, entomological variables, such as entomological inoculation rate, were not strong predictors of human incidence in this context. Finally, the study explores the predictors of spatial variation in malaria, considering land use, intervention, and entomological variables. The findings contribute to a better understanding of malaria transmission dynamics at local scales, aiding in the development of effective control strategies in endemic regions.
Catégories: Actus Santé

Using the Public Health and Social Measures Severity Index for analysing government responses during the COVID-19 pandemic in the WHO European Region

mer, 22/11/2023 - 00:00
Public health and social measures (PHSM), such as adaptions to the operation of schools, businesses and workplaces, international travel measures and restrictions on gatherings and people's movements, as well as individual preventive measures such as physical distancing, have been a vital set of tools utilized by many countries to mitigate the spread of SARS-CoV-2 virus throughout the COVID-19 pandemic. In January 2020, the WHO Regional Office for Europe started to systematically monitor, collect and categorize data on response measures taken by its Member States. In order to visualize and analyse the collected data, WHO developed a methodology for quantifying the response measures into an index, capturing the severity of these policy measures in terms of six key indicators. The aim of this article is to describe the methodology underlying the index, including data collection, categorization and calculation, in order to provide researchers and policy-makers with a better understanding of its application. Furthermore, it provides an overview and examples of possible applications of the index, as well as serve as a reference for subsequent research on the effectiveness of PHSM, including empirical studies and models that can help to guide health policies, their timing and severity.
Catégories: Actus Santé

Geographic accessibility to public healthcare facilities and spatial clustering during the wet and dry seasons in Cote d'Ivoire

mer, 22/11/2023 - 00:00
Introduction Geographic accessibility to healthcare is a key determinant of health outcomes. Yet, globally, over 4.5 billion people lack access to healthcare, majority of which are located in low and middle income countries. While metrics of spatial access should consider variation in seasonality, studies in Cote d'Ivoire have overlooked seasonality impacts and how such metrics are spatially clustered. Here, we assessed geographical accessibility to public health care in Cote d'Ivoire across wet and dry seasons while assessing clustering and identifying marginalized populations. Methods We assembled spatial data on the location of public healthcare facilities, factors that affect travel, population distribution, and healthcare seeking behaviour. Using these datasets, plausible travel scenarios reflecting seasonality were combined within a cost distance algorithm in AccessMod (version 5) to model travel time to the nearest facility at 1km resolution for dry and wet seasons. We determined the proportion of the population within 2 hours' travel time at the district level. We assessed marginalization (more than 4 hours from the nearest facility) and spatial autocorrelation using Morans I indices. Results At the national level, mean travel time to the nearest public healthcare facility was 1.8h during the dry season and 3.4h during the wet season. The travel times were heterogeneous and varied between 23min to 6h and 38min to 10h during both seasons. About 73% (7 to 98%) of the population was within 2h of the nearest public healthcare facility in the dry season and 55% (2 to 97%) during the wet season at the district level. Poor access clusters were in the north and better access clusters in the south central area of the country during both seasons. Conclusion Healthcare access inequalities in Cote d'Ivoire persist, with inadequate access clusters in the north and better access in the south central region. There is a need for seasonal based targeted interventions to improve access.
Catégories: Actus Santé

Early-onset schizophrenia is associated with immune-related rare variants in a Chinese sample

mer, 22/11/2023 - 00:00
Background: Rare variants are likely to contribute to schizophrenia (SCZ), given the large discrepancy between the heritabilities estimated from twin and GWAS studies. Furthermore, the nature of the rare-variant contribution to SCZ may differ according to "age-at-onset" (AAO), since early-onset has been suggested as being indicative of neurodevelopment deviance. Objective: To examine the association of rare deleterious coding variants in early- and adult-onset SCZ in a Chinese sample. Method: Exome sequencing was performed on DNA from 197 patients with SCZ spectrum disorder and 82 healthy controls (HC) of Chinese ancestry recruited in Hong Kong. We also gathered AAO information in the majority of SCZ samples. Patients were classified into early-onset (EOS, AAO<18) and adult-onset (EOS, AAO<18). We collapsed the rare variants to improve statistical power and examined the overall association of rare variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels by Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was also conducted. We focused on variants which are predicted to have a medium or high impact on the protein-encoding process as defined by Ensembl. We applied a 100000-time permutation test to obtain empirical p-values, with significance threshold set at p < 1e-3 to control family-wise error rates. Moreover, we compared the burden of variants of the labelled consequence in significant risk genes and gene sets in cases and controls. Results: Based on several binary-trait association tests (i.e., SCZ vs HC, EOS vs HC and AOS vs HC), we identified 7 candidate risk genes and 20 gene ontology biological processes (GOBP) terms, which exhibited higher burdens in SCZ than in controls. Based on quantitative rare-variant association tests, we found that alterations in 5 candidate risk genes and 7 GOBP pathways were significantly correlated with AAO. Based on biological and functional profiles of the candidate risk genes and gene sets, our findings suggested that perturbations in neural systems are involved in SCZ, yet altered immune responses may be specifically implicated in EOS. Conclusion: Disrupted immune responses may worsen the neural perturbations during neurodevelopment and may advance the onset age of SCZ. We provided evidence of rare variants increasing SCZ risk in the Chinese setting.
Catégories: Actus Santé

Validating the efficacy and value proposition of Mental Fitness Vocal Biomarkers in a psychiatric population: prospective cohort study

mer, 22/11/2023 - 00:00
This study represents a practical advancement in the application of vocal biomarkers for mental health tracking in real-world settings. Through a prospective cohort study involving 104 participants from an outpatient psychiatric population, we introduced a novel "Mental Fitness Vocal Biomarker" (MFVB) score, derived from eight preselected vocal features supported by literature review. Our findings demonstrate the MFVB's efficacy in objectively stratifying individuals based on risk for elevated mental health symptom severity using the M3 Checklist for transdiagnostic assessment (depression, anxiety, post-traumatic stress disorder, and bipolar) as reference standard. Continuous observation over time significantly improves efficacy, yielding a risk ratio of 1.53 (1.09-2.14, p=0.0138) for single 30-second voice samples to 2.00 (1.21-3.30, p=0.0068) for 2-week aggregations, depending on MFVB score. Notably, in the highly engaged subgroup (5-6 MFVB uses per week, 38% of participants), a risk ratio of 8.50 (2.31-31.25, p=0.0013) was observed, underscoring the utility of frequent and continuous observation. Participant feedback confirmed the user-friendliness of the application and perceived benefits, highlighting the MFVB's potential as a cost-effective, scalable, and privacy-preserving adjunct to traditional psychiatric assessments. These results establish that vocal biomarkers are a promising tool for objective mental health tracking in real-world conditions, offering personalized insights into users' mental well-being as they engage with clinical therapy or other beneficial activities that are associated with improved mental health risks and outcomes.
Catégories: Actus Santé

Childhood trajectories of emotional and behavioral difficulties are related to polygenic liability for mood and anxiety disorders

mer, 22/11/2023 - 00:00
Background: Symptoms related to mood and anxiety disorders often present in childhood and adolescence. Some of the genetic liability for mental disorders, and emotional and behavioral difficulties seems to be shared. Yet, it is unclear how genetic liability for mood and anxiety disorders influence trajectories of childhood emotional and behavioral difficulties, and if specific developmental patterns associate with higher genetic liability for these disorders. Methods: This study uses data from a genotyped sample of children (n = 54,839) from the Norwegian Mother, Father and Child Cohort Study (MoBa). We use latent growth models (1.5-5 years) and latent profile analyses (1.5-8 years) to quantify childhood trajectories and profiles of emotional and behavioral difficulties and diagnoses. We examine associations between these trajectories and profiles with polygenic scores for bipolar disorder (PGSBD), anxiety (PGSANX), depression (PGSDEP), and neuroticism (PGSNEUR). Results: Associations between PGSDEP, PGSANX and PGSNEUR, and emotional and behavioral difficulties in childhood were developmentally stable rather than age specific. Higher PGSANX and PGSDEP were associated with steeper increases in behavioral difficulties across early childhood. Latent profile analyses identified five profiles. All PGS were associated with probability of classification into profiles characterized by some form of difficulties (vs. a normative reference profile), but only PGSBD was uniquely associated with a single developmental profile. Conclusions: Our findings indicate that genetic risk for mood disorders and related traits contribute to a more rapidly increasing and higher overall burden of emotional and behavioral difficulties across early and middle childhood, with some indications for disorder-specific profiles. These findings of associations between childhood trajectories and symptom profiles and genetic and clinical susceptibility for mental disorders, may form the basis for more targeted early interventions.
Catégories: Actus Santé

ChatGPT for assessing risk of bias of randomized trials using the RoB 2.0 tool: A methods study

mer, 22/11/2023 - 00:00
Background: The assessment of risk of bias is a critical component of systematic review methods. Assessing risk of bias, however, can be time- and resource-intensive. AI-based solutions may increase efficiency and reduce burden. Objective: To evaluate the reliability of ChatGPT for performing risk of bias assessments of randomized trials. Methods: We sampled recently published Cochrane systematic reviews of medical interventions (up to October 2023) that included randomized controlled trials and assessed risk of bias using the Cochrane-endorsed revised risk of bias tool for randomized trials (RoB 2.0). From each eligible review, we collected data on the risk of bias assessments for the first three reported outcomes. Using ChatGPT-4, we assessed the risk of bias for the same outcomes using three different prompts: a minimal prompt including limited instructions, a maximal prompt with extensive instructions, and an optimized prompt that was designed to yield the best risk of bias judgments. The agreement between ChatGPT's assessments and those of the systematic reviewers was quantified using weighted kappa statistics. Results: We included 34 systematic reviews with 157 unique trials. We found the agreement between ChatGPT and systematic review authors for assessment of overall risk of bias to be 0.16 (95% CI: 0.01 to 0.3) for the maximal ChatGPT prompt, 0.17 (95% CI: 0.02 to 0.32) for the optimized prompt, and 0.11 (95% CI: -0.04 to 0.27) for the minimal prompt. For the optimized prompt, agreement ranged between 0.11 (95% CI: -0.11 to 0.33) to 0.29 (95% CI: 0.14 to 0.44) across risk of bias domains, with the lowest agreement for the deviations from the intended intervention domain and the highest agreement for the missing outcome data domain. Conclusion: Our results suggest that ChatGPT and systematic reviewers only have slight to fair agreement in risk of bias judgments for randomized trials. ChatGPT is currently unable to reliably assess risk of bias of randomized trials. We recommend systematic reviewers avoid using ChatGPT to perform risk of bias assessments.
Catégories: Actus Santé

Gender based disparity in performing aortic valve surgery in the united state before availability of percutaneous valve implantation

mer, 22/11/2023 - 00:00
Background: Aortic valve surgery has been performed increasingly in high-risk patients. The goal of this study was to evaluate this trend based on gender in the United States before the availability of percutaneous aortic valve replacement. Method: The Nationwide Inpatient Sample (NIS) database was utilized to calculate the age-adjusted utilization rate for aortic valve surgery from 1988 to 2011 in the United States using ICD-9 coding for aortic valve surgery Results: A total population of 258, 506 patients underwent aortic valve between 1988-2011 were available for our study over the age of 20. We found that the age-adjusted rate of aortic valve surgery gradually increased from 1988 until 2009 and stabilized thereafter with a persistently higher rate for men. For men age-adjusted rate in 1988 was 13.3 per 100,000 vs. 27.0 in year in the year 2011 per 100,000. For women, the age-adjusted rate in 1988 was 6.07 per 100,000 vs. 11.4 in year 2011 per 100.000). Conclusion: Aortic valve surgery utilization has stabilized in recent years in both genders in the United States. However, this rate has been persistently more than double in men. The cause of this higher utilization in males needs further investigation.
Catégories: Actus Santé

Comparison of troponin and natriuretic peptides in takotsubo syndrome and acute coronary syndrome: a meta-analysis

mer, 22/11/2023 - 00:00
Background: Takotsubo syndrome (TTS) is an acute heart failure syndrome which resembles acute coronary syndrome (ACS) at presentation. Differentiation requires coronary angiography, but where this does not occur immediately, cardiac biomarkers may provide additional utility. We performed a meta-analysis to compare troponin and natriuretic peptides (NPs) in TTS and ACS to determine if differences in biomarker profile can aid diagnosis. Methods: We searched five literature databases for studies reporting NPs (BNP/NT-pro-BNP) or troponin I/T in TTS and ACS, identifying 28 studies for troponin/NPs (5618 and 1145 patients respectively). Results: Troponin was significantly lower in TTS than ACS (standardized mean difference (SMD) -0.86; 95% CI -1.08- -0.64; p<0.00001), with an absolute difference of 75 times the upper limit of normal (xULN) higher in ACS than TTS. Conversely, NPs were significantly higher in TTS (SMD 0.62; 0.44-0.80; p<0.00001) and 5.8xULN greater absolutely. Area under the curve (AUC) for troponin in ACS versus TTS was 0.82 (0.70-0.93), and 0.92 (0.80-1.00) for STEMI vs. TTS. For NPs, AUC was 0.69 (0.48-0.89). Combination of troponin and NPs with logistic regression did not improve AUC. Recursive partitioning and regression tree analysis calculated a troponin threshold ?26xULN that identified 95% cases as ACS where and specificity for ACS were 85.71% and 53.57% respectively, with 94.32% positive predictive value and 29.40% negative predictive value. Conclusions: Troponin is lower and NPs higher in TTS versus ACS. Troponin had greater power than NPs at discriminating TTS and ACS, and with troponin [≥]26xULN patients are far more likely to have ACS.
Catégories: Actus Santé

Testing-isolation interventions will likely be insufficient to contain future novel disease outbreaks

mar, 21/11/2023 - 00:00
When novel human diseases emerge into naive populations, identification and isolation of infected individuals forms the first line of defense against the invading pathogens. Diagnostic testing plays a critical role, but health agencies unprepared for a novel disease invasion may struggle to meet the massive testing capacities demanded by an epidemic outbreak, potentially resulting in a failure of epidemic containment as with COVID-19. What factors make a disease controllable versus uncontrollable with limited testing supplies remains unclear. Specifically, is the failure of testing-isolation unique to COVID-19, or is this a likely outcome across the spectrum of disease traits that may constitute future epidemics? Here, using a generalized mathematical disease model parameterized for each of seven different human diseases, we show that testing-isolation strategies will typically fail to contain epidemic outbreaks at practicably achievable testing capacities. From this analysis, we identify three key disease characteristics that govern controllability under resource constraints; the basic reproduction number, mean latent period, and non-symptomatic transmission index. Interactions among these characteristics play prominent roles in both explaining controllability differences among diseases and enhancing the efficacy of testing-isolation in combination with transmission-reduction measures. This study provides broad guidelines for managing controllability expectations during future novel disease invasions, describing which classes of diseases are most amenable to testing-isolation strategies alone and which will necessitate additional transmission-reduction measures like social distancing.
Catégories: Actus Santé

ERBB2 R599C variant is associated with left ventricular outflow tract obstruction defects in human

mar, 21/11/2023 - 00:00
Background and aims Non-syndromic congenital heart defects (CHD) are occasionally familial and left ventricular out flow tract obstruction (LVOTO) defects are among the subtypes with the highest hereditability. The aim of this study was to evaluate the pathogenicity of a heterozygous ERBB2 variant R599C identified in three families with LVOTO defects. Methods Variant detection was done with exome sequencing. Western blotting, digital PCR, mass spectrometry (MS), MS-microscopy and flow cytometry were used to study the function of the ERBB2 variant R599C. Cardiac structure and function were studied in zebrafish embryos expressing human ERBB2 WT or R599C. Patient-derived human induced pluripotent stem cell cardiomyocytes (hiPS-CM) and endothelial cells (hiPS-ECs) were used for transcriptomic analyses. Results While phosphorylation of the ERBB2 R599C receptor was not altered, the variant affected dramatically the binding partners of the protein and lead to mislocalization of ERBB2 from plasma membrane to ER and mitochondria. Expression of human ERBB2 R599C in zebrafish embryos resulted in cardiomyocyte hypertrophy, increased cardiac wall thickness, and impaired fractional shortening, demonstrating that the mutant receptor induces functional and structural defects during heart development. Transcriptomic analyses of hiPS-ECs and hiPS-CMs from a patient with the R599C variant indicated aberrant expression of genes related to cardiovascular system development and abnormal response to oxidative stress in both cell types. Conclusion The heterozygous variant ERBB2 R599C leads to abnormal cellular localization of the ERBB2 receptor inducing structural changes and dysfunction in the zebrafish embryo heart. This evidence suggests ERBB2 as a novel disease gene for CHD.
Catégories: Actus Santé

Early recovery of leukocyte subsets is associated with progression-free survival in patients with inoperable stage III NSCLC after multimodal treatment: a prospective explorative study

mar, 21/11/2023 - 00:00
Background We explored the dynamic changes of major leukocyte subsets during definitive treatment of patients with inoperable stage III NSCLC lung cancer and correlated it to survival to identify subpopulations associated with maximal patient benefit. Methods We analyzed peripheral blood of 20 patients, either treated with thoracic radiotherapy (RT), concurrent chemo-radiotherapy (cCRT), or cCRT with additional immune-checkpoint inhibition therapy. Blood samples were collected at 9 timepoints before, during, and up to 1 year post treatment and analyzed by multi-color flow cytometry. Statistical analysis was conducted for leukocyte subpopulations, IL-6, progression-free survival (PFS) and overall survival (OS). Results Increase of absolute lymphocyte counts (ALC) after the end of RT until 6 months thereafter was a predictor of PFS. Baseline lymphocyte counts showed no significant correlation to PFS or OS. Early recovery of absolute counts (AC) at 3 weeks after RT, total CD3+ T-cells, and CD8+ cytotoxic T-cells distinguished those patients with favorable PFS ([≥]12 months) from all other patients. Discriminant analysis identified B-cells, neutrophil-lymphocyte-ratio (NLR), CD4+ T-helper-cells, and NK-cells as predictors of favorable PFS. High variability in IL-6 plasma concentration of consecutive measurements within 6 months after the end of RT correlated negatively with PFS. Conclusion Our results suggest that two parameters commonly assessed in clinical routine, can be used to predict patient outcome. These are: early increase in CD8+ T-cell lymphocyte-count and variability in IL-6 plasma concentration, that are correlated to patients with favorable, respectively, poor outcome after definitive therapy independent of treatment regimen.
Catégories: Actus Santé

The Effects of Progressive Resistance Strength Training on Pain, Mobility and Activities of Daily Living among Knee Osteoarthritis Patients: A randomized controlled trial

mar, 21/11/2023 - 00:00
Purpose Knee osteoarthritis (OA) is a degenerative and weight-bearing joint disease that resulted from wear and tear of articular cartilage and its underlying bone. It is more common in overweight and obese knee OA patients. The purpose of this study was to investigate the effects of progressive resistance strength training of lower limb rehabilitation protocol (LLRP) on pain, activities of daily living (ADL) and mobility among knee OA patients who are overweight or obese. Methods Fifty-six overweight or obese knee OA patients were included and randomly assigned to a Rehabilitation Protocol Group (RPC) or Control Group (CG). The patients in the RPG performed the progressive resistance strength training of LLRP and followed the instructions of daily care (IDC) for duration of twelve weeks at home. The patients in the CG followed the IDC (conventional treatment) only. Outcome measures were assessed at baseline and after the interventions in both groups by comparing Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score for pain, Timed Up and Go (TUG) test score for mobility and Katz Index of Independence scores for ADL. Results The patients in the RPG reported significant improvements in WOMAC score for pain (p = 0.001), Katz Index of Independence scores for ADL (p = 0.003) and TUG test score for mobility (p = 0.004). The patients in the CG also reported significant improvements in WOMAC score for pain (p = 0.002) and ADL (p = 0.052), but not in mobility score (p = 0.065). The improvement in the pain and ADL scores was greater in the patients of RPG than the CG with p-value of 0.001 and 0.000 respectively. Conclusions The progressive resistance strength training of LLRP is effective in terms of reducing pain, improving mobility and ADL among knee OA patients who are overweight or obese.
Catégories: Actus Santé

Affect and post-COVID-19 symptoms in daily life: An exploratory experience sampling study

mar, 21/11/2023 - 00:00
Insight into the daily life experiences of patients with post-COVID-19 syndrome is lacking. The current study explored temporal fluctuations of and associations between positive and negative affect and symptoms throughout the day in previously hospitalised post-COVID-19 patients using an experience sampling methodology. Ten participants (age: median = 60, interquartile range = 9 years; 50% women ; 80% [≥]1 comorbidity; 8-12 months since hospital discharge) filled out brief online questionnaires, six times a day for 14 consecutive days. Positive and negative affect, and self-reported symptoms (physical and mental fatigue, cognitive functioning, dyspnoea, and pain) were assessed in real-time. Primarily, graphs were analysed to assess the individual longitudinal courses of and (concurrent and time-lagged) associations between affect and symptoms. Secondly, correlations or multilevel linear regression models were used to support these interpretations. Visual assessment showed limited temporal fluctuation in affect and symptoms. All symptoms appeared to associate positively with each other (correlations between .26 and .85). Positive affect was associated with lower symptoms severity ({beta}s between -.28 and -.67), and negative affect with higher symptoms severity ({beta}s between .24 and .66). Time-lagged analyses showed that - adjusted for residual symptom severity of prior measurements - both types of affect predicted symptom severity two hours later ({beta}s between -.09 and -.31 for positive affect; between .09 and .28 for negative affect). These findings suggest that positive and negative affect may play important roles in post-COVID-19 symptom experience and temporal fluctuation.
Catégories: Actus Santé

A protracted cholera outbreak in Nairobi City County associated with mass gathering events, Kenya, 2017

mar, 21/11/2023 - 00:00
Cholera continues to cause many outbreaks in low and middle-income countries due to inadequate water, sanitation, and hygiene services. We describe a protracted cholera outbreak in Nairobi City County (NCC), Kenya in 2017. We reviewed the cholera outbreak line lists from NCC in 2017 to determine its extent and factors associated with death. A suspected case of cholera was any person aged >2 years old who had acute watery diarrhea, nausea, or vomiting, whereas a confirmed case was where Vibrio cholerae was isolated from the stool specimen. We summarized cases using for continuous variables and proportions for categorical variables. Associations between admission status, sex, age, residence, time to care seeking, and outbreak settings; and cholera associated deaths were assessed using odds ratio (OR) with 95% confidence interval (CI). Of the 2,737 cholera cases reported, we analyzed 2,347 (85.7%) cases including 1,364 (58.1%) outpatients, 1,724 (73.5%) not associated with mass gathering events (MGEs), 1,356 (57.8%) male and 2,202 (93.8%) aged >=5 years, and 35 deaths (case fatality rate: 1.5%). Cases were reported from all the Sub Counties of NCC with an overall county attack rate of 50 per 100,000 people. Vibrio cholerae Ogawa serotype was isolated from 78 (34.8%) of the 224 specimens tested and all isolates were sensitive to tetracycline and levofloxacin but resistant to amikacin. The odds of cholera-related deaths was lower among outpatient cases (aOR: 0.35; [95% CI: 0.17- 0.72]), age >=5 years old (aOR: 0.21 [95% CI: 0.09-0.55]), and MGEs (aOR: 0.26 [95% CI: 0.070.91]) while threefold higher odds among male (aOR: 3.04 [95% CI: 1.30-7.13]). NCC experienced a protracted and widespread cholera outbreak with a high case fatality rate in 2017.
Catégories: Actus Santé

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