Survival advantage of hemodialysis relative to peritoneal dialysis in patients with end-stage renal disease and congestive heart failure

Peritoneal dialysis (PD) has been proposed as a therapeutic option for patients with end-stage renal disease and associated congestive heart failure (CHF). Here, we compare mortality risks in these patients by dialysis modality by including all patients who started planned chronic dialysis with associated congestive heart failure and were prospectively enrolled in the French REIN Registry. Survival was compared between 933 PD and 3468 hemodialysis (HD) patients using a Kaplan–Meier model, Cox regression, and propensity score analysis. The patients were followed from their first dialysis session and stratified by modality at day 90 or last modality if death occurred prior. There was a significant difference in the median survival time of 20.4 months in the PD group and 36.7 months in the HD group (hazard ratio, 1.55). After correction for confounders, the adjusted hazard ratio for death in PD compared to the HD patients remained significant at 1.48. Subgroup analyses showed that the results were not changed with regard to the New York Heart Association stage, age strata, or estimated glomerular filtration rate strata at first renal replacement therapy. The use of propensity score did not change results (adjusted hazard ratio, 1.55). Thus, mortality risk was higher with PD than with HD among incident patients with end-stage renal disease and congestive heart failure. These results may help guide clinical decisions and also highlight the need for randomized clinical trials

Stroke care in Brazil and France : national policies and healthcare indicators comparison

Objective: To identify the commonalities and discrepancies between national health policies to combat stroke in France and Brazil. Justification: Both healthcare systems were structured as universal access and comprehensive care attention, hierarchized by the level of care, politically and administratively decentralized. France is an industrialized, high-income country, with health care involving copayment and reimbursement of expenses, and spontaneous demand for services. Brazil is a member of the BRICs, of upper middle income with totally free health care, with an active search for hypertension and diabetes in the general population. Methods: Data regarding policies, risk factors, and health indicators about stroke care, from 2010 to 2017, were obtained from both countries (publicly accessible information or on request) from the respective Ministries of Health or international agencies. Results: About acute stroke hospitalizations, on average, Brazil has 0.75 per 1000 annual population hospitalizations versus 1.54 per 1000 in France. Brazil has 0.21 per 1000 population deaths per year versus 0.40 per 1000 in France. The in-hospital mortality rate in Brazil has 139 per 1000 hospitalized people versus 263 in France. The average length of stay of acute hospitalizations was 7.6 days in Brazil versus 12.6 in France. The prevalence of strokes by age group shows from 0 to 39 years old (this rate is stable); 40–59 years (it is increasing in both countries); and 60–79 and 80+ years (this rate has been increasing in France and decreasing in Brazil). Conclusion: No major differences were found about the health policies and the National Health Plans related to stroke. However, the data directly linked to the period of hospitalization differed substantially between countries. Subsequent studies can be implemented to identify the explanatory factors, notably among the risk factors and actions in primary care, and the moments after hospital care, such as secondary prevention and palliative care

Emergency Room Evaluation and Recommendations and Risk Screening of Incident Major Neurocognitive Disorders in Older Females: Results of an Observational Population-Based Cohort Study

Background“Emergency Room Evaluation and Recommendations” (ER2) risk levels (i.e., low, moderate and high) may be used to screen for major neurocognitive disorders (MNCD) in older emergency department users, as a high ER2 risk level is associated with MNCD diagnosis. This study aims to examine the association of ER2 risk levels with incident MNCD in community-dwelling older adults.MethodsA total of 709 participants of the EPIDémiologie de l’OStéoporose (EPIDOS) study—an observational population-based cohort study—were recruited in Toulouse (France). ER2 low, moderate and high risk levels were determined at baseline. Incident MNCD and their type (i.e., Alzheimer’s disease (AD) vs. non-AD) were diagnosed after a 7-year follow-up period.ResultsThe overall incidence of MNCD was 29.1%. A low ER2 risk level was associated with low incidence of MNCD [Hazard ratio (HR) = 0.71 with P = 0.018] and AD (HR = 0.56 with P = 0.003), whereas a high risk level, both individually and when combined with a moderate risk level, was associated with high incidence of MNCD (HR ≥ 1.40 with P ≤0.018) and AD (HR ≥ 1.80 with P ≤ 0.003). No association was found with incident non-AD.ConclusionER2 risk levels were positively associated with incident MNCD in EPIDOS participants, suggesting that ER2 may be used for risk screening of MNCD in the older population

Critical care staffing ratio and outcome of COVID-19 patients requiring intensive care unit admission during the first pandemic wave: a retrospective analysis across Switzerland from the RISC-19-ICU observational cohort

STUDY AIM: The surge of admissions due to severe COVID-19 increased the patients-to-critical care staffing ratio within the ICUs. We investigated whether the daily level of staffing was associated with an increased risk of ICU mortality (primary endpoint), length of stay (LOS), mechanical ventilation and the evolution of disease (secondary endpoints). METHODS: We employed a retrospective multicentre analysis of the international Risk Stratification in COVID-19 patients in the ICU (RISC-19-ICU) registry, limited to the period between March 1 and May 31, 2020, and to Switzerland. Hierarchical regression models were used to investigate crude and adjusted effects of the critical care staffing ratio on study endpoints. We adjusted for disease severity and weekly caseload. RESULTS: Among the 38 participating Swiss ICUs, 17 recorded staffing information. The study population included 437 patients and 2,342 daily assessments of patient-to-critical care staffing ratio. Median of daily patient-to-nurse ratio started at 1.0 [IQR 0.5–1.5; calendar week 9] and peaked at 2.4 (IQR 0.4–2.0; calendar week 16), while the median of daily patient-to-physician ratio started at 4.0 (IQR 2.1–5.0; calendar week 9) and peaked at 6.8 (IQR 6.3–7.3; calendar week 19). Neither the patient-to-nurse (adjusted OR 1.28, 95% CI 0.85–1.93; doubling of ratio) nor the patient-to-physician ratio (adjusted OR 1.07, 95% CI 0.87–1.32; doubling of ratio) were associated with ICU mortality. We found no association of daily critical care staffing on the secondary endpoints in adjusted models. CONCLUSION: We found no association of reduced availability of critical care staffing resources in Swiss ICUs with overall ICU length of stay nor mortality. Whether long-term outcome of critically ill patients with COVID-19 have been affected remains to be studied

Critical care staffing ratio and outcome of COVID-19 patients requiring intensive care unit admission during the first pandemic wave: a retrospective analysis across Switzerland from the RISC-19-ICU observational cohort.

STUDY AIM The surge of admissions due to severe COVID-19 increased the patients-to-critical care staffing ratio within the ICUs. We investigated whether the daily level of staffing was associated with an increased risk of ICU mortality (primary endpoint), length of stay (LOS), mechanical ventilation and the evolution of disease (secondary endpoints). METHODS We employed a retrospective multicentre analysis of the international Risk Stratification in COVID-19 patients in the ICU (RISC-19-ICU) registry, limited to the period between March 1 and May 31, 2020, and to Switzerland. Hierarchical regression models were used to investigate crude and adjusted effects of the critical care staffing ratio on study endpoints. We adjusted for disease severity and weekly caseload. RESULTS Among the 38 participating Swiss ICUs, 17 recorded staffing information. The study population included 437 patients and 2,342 daily assessments of patient-to-critical care staffing ratio. Median of daily patient-to-nurse ratio started at 1.0 [IQR 0.5-1.5; calendar week 9] and peaked at 2.4 (IQR 0.4-2.0; calendar week 16), while the median of daily patient-to-physician ratio started at 4.0 (IQR 2.1-5.0; calendar week 9) and peaked at 6.8 (IQR 6.3-7.3; calendar week 19). Neither the patient-to-nurse (adjusted OR 1.28, 95% CI 0.85-1.93; doubling of ratio) nor the patient-to-physician ratio (adjusted OR 1.07, 95% CI 0.87-1.32; doubling of ratio) were associated with ICU mortality. We found no association of daily critical care staffing on the secondary endpoints in adjusted models. CONCLUSION We found no association of reduced availability of critical care staffing resources in Swiss ICUs with overall ICU length of stay nor mortality. Whether long-term outcome of critically ill patients with COVID-19 have been affected remains to be studied

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.

IMPORTANCE: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. OBJECTIVE: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. DESIGN, SETTING, AND PARTICIPANTS: This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. EXPOSURES: Case-control studies. MAIN OUTCOMES AND MEASURES: Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. RESULTS: This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006). CONCLUSIONS AND RELEVANCE: In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS

Evolution of Susceptibility to Ingested Double-Stranded RNAs in Caenorhabditis Nematodes

International audienceBACKGROUND: The nematode Caenorhabditis elegans is able to take up external double-stranded RNAs (dsRNAs) and mount an RNA interference response, leading to the inactivation of specific gene expression. The uptake of ingested dsRNAs into intestinal cells has been shown to require the SID-2 transmembrane protein in C. elegans. By contrast, C. briggsae was shown to be naturally insensitive to ingested dsRNAs, yet could be rendered sensitive by transgenesis with the C. elegans sid-2 gene. Here we aimed to elucidate the evolution of the susceptibility to external RNAi in the Caenorhabditis genus. PRINCIPAL FINDINGS: We study the sensitivity of many new species of Caenorhabditis to ingested dsRNAs matching a conserved actin gene sequence from the nematode Oscheius tipulae. We find ample variation in the Caenorhabditis genus in the ability to mount an RNAi response. We map this sensitivity onto a phylogenetic tree, and show that sensitivity or insensitivity have evolved convergently several times. We uncover several evolutionary losses in sensitivity, which may have occurred through distinct mechanisms. We could render C. remanei and C. briggsae sensitive to ingested dsRNAs by transgenesis of the Cel-sid-2 gene. We thus provide tools for RNA interference studies in these species. We also show that transgenesis by injection is possible in many Caenorhabditis species. CONCLUSIONS: The ability of animals to take up dsRNAs or to respond to them by gene inactivation is under rapid evolution in the Caenorhabditis genus. This study provides a framework and tools to use RNA interference and transgenesis in various Caenorhabditis species for further comparative and evolutionary studies

Incidence of Sarcoma Histotypes and Molecular Subtypes in a Prospective Epidemiological Study with Central Pathology Review and Molecular Testing

International audienceBACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes) of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000), unclassified sarcoma (16%; 1/100,000), liposarcoma (15%; 0.9/100,000) and leiomyosarcoma (11%; 0.7/100,000). CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas

Natural and Experimental Infection of Caenorhabditis Nematodes by Novel Viruses Related to Nodaviruses

Novel viruses have been discovered in wild Caenorahbditis nematode isolates and can now be used to explore host antiviral pathways, nematode ecology, and host-pathogen co-evolution