Liver diseases are associated with profound hemostatic changes proportional to severity of illness. Hemostatic changes in acute‐on‐chronic liver failure (ACLF) may in part reflect critical illness. Hemostatic changes in ACLF partly overlap with those in sepsis, with rebalanced hemostasis in both. Patients with sepsis had hyperfibrinogenemia, associated with a thrombogenic clot structure. Abstract BackgroundEven the sickest patients with chronic liver disease (CLD), such as those with acute‐on‐chronic liver failure (ACLF) remain in hemostatic balance due to a concomitant decline in pro‐ and antihemostatic factors. ObjectivesWe aimed to study whether the hemostatic status in ACLF is merely an exaggeration from the status in patients with compensated and acutely decompensated cirrhosis, or whether sepsis‐associated hemostatic changes contribute. MethodsWe performed extensive hemostatic profiling in 31 adult patients with ACLF, 20 patients with sepsis without underlying CLD, and 40 healthy controls. ResultsWe found similarly elevated plasma levels of the platelet adhesive protein von Willebrand factor (VWF) and decreased levels of the VWF‐regulating protease ADAMTS13 in both groups compared to healthy controls. In vivo markers of activation of coagulation (thrombin‐antithrombin III, D‐dimer) were similarly elevated in both groups compared to controls, but ex vivo thrombin‐generating capacity was similar between patients and controls, despite a much more profound international normalized ratio elevation in ACLF. Plasma fibrinogen levels were much higher in septics, which was accompanied by a decreased ex vivo clot permeability and an increase in ex vivo resistance to clot lysis. All hemostatic parameters were remarkably stable over the first 10 days after admission. ConclusionsWe have found hemostatic changes in ACLF to partially overlap with that of patients with sepsis, and evidence of preserved hemostatic capacity in both patient groups. The notable difference was a profound hyperfibrinogenemia, associated with a thrombogenic clot structure and a marked ex vivo resistance to fibrinolysis in patients with sepsis.
Context: Workforce development in governmental public health has historically focused on discipline-specific skills. However, as the field of public health has evolved, crosscutting skills have become critical. The 2017 fielding of the Public Health Workforce Interests and Needs Survey (PH WINS) provides a national benchmark for gaps in crosscutting skills in state and local health departments. Objective: The purpose of this article is to identify top areas of training needs in the governmental public health workforce using data from PH WINS 2017. Design: PH WINS participants in state and local health departments were surveyed in fall 2017 using a Web-based platform. Balanced repeated replication weights were used to account for complex sample design. Setting: Forty-seven state health agencies, 26 large city health departments, and a nationally representative sample of mid-to-large local health departments. Participants: Permanently employed governmental public health staff. Main Outcome Measures: Training needs were determined by combining self-reported skill importance and proficiency. Skills reported to be of high importance, and low levels of proficiency were coded as training needs. Focus area gaps were defined as having a training need in at least one skill in the focus area. Results: The largest area of training need, regardless of supervisory status, was in budgeting and financial management (55%; 95% confidence interval [CI], 53-56), with a large gap also identified in systems and strategic thinking (49%; 95% CI, 47-50). There was some variation by supervisory status, with training needs for nonsupervisors in change management and in developing a vision for a healthy community for management. Conclusions: The PH WINS training needs assessment provides the first nationally representative data on training needs for the state and local health department workforce. Across state and local health departments, there are common critical training needs essential for the current and future practice of public health.
BackgroundSuicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested.MethodsDNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions.ResultsOur analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse.ConclusionPreliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
Recently, a significant epigenetic component in the pathology of suicide has been realized. Here we investigate candidate functional SNPs in epigenetic-regulatory genes, DNMT1 and DNMT3B, for association with suicide attempt (SA) among patients with co-existing psychiatric illness. In addition, global DNA methylation levels [5-methyl cytosine (5-mC%)] between SA and psychiatric controls were quantified using the Methylflash Methylated DNA Quantification Kit. DNA was obtained from blood of 79 suicide attempters and 80 non-attempters, assessed for DSM-IV Axis I disorders. Functional SNPs were selected for each gene (DNMT1; n = 7, DNMT3B; n = 10), and genotyped. A SNP (rs2424932) residing in the 3 UTR of the DNMT3B gene was associated with SA compared with a non-attempter control group (P = 0.001; Chi-squared test, Bonferroni adjusted P value = 0.02). Moreover, haplotype analysis identified a DNMT3B haplotype which differed between cases and controls, however this association did not hold after Bonferroni correction (P = 0.01, Bonferroni adjusted P value = 0.56). Global methylation analysis showed that psychiatric patients with a history of SA had significantly higher levels of global DNA methylation compared with controls (P = 0.018, Student's t-test). In conclusion, this is the first report investigating polymorphisms in DNMT genes and global DNA methylation quantification in SA risk. Preliminary findings suggest that allelic variability in DNMT3B may be relevant to the underlying diathesis for suicidal acts and our findings support the hypothesis that aberrant DNA methylation profiles may contribute to the biology of suicidal acts. Thus, analysis of global DNA hypermethylation in blood may represent a biomarker for increased SA risk in psychiatric patients.Keywords: DNA methylation, DNA methyltransferases, epigenetics, polymorphisms, psychiatry, suicide Suicide is a worldwide public health problem and a leading cause of death among young people in developed countries. Every year, almost one million people die from suicide globally with suicide attempts (SAs) up to 20 times more frequent than completed suicide (World Health Organization 2012). The risk for suicidal acts is multi-factorial, and consists of a range of biological, psychiatric, psychosocial, interpersonal and cultural risk factors.In addition to classical genetic abnormalities, an epigenetic component in the pathology of suicide has been realized. Epigenetics can be defined as the mechanisms that initiate and maintain heritable patterns of gene expression without altering the sequence of the genome (Holliday 1987). There are several layers of epigenetic complexity including histone modifications, chromatin remodelling and DNA methylation, the latter being the most thoroughly studied to date (Esteller 2006). DNA methylation refers to the addition of a methyl group to the carbon at position 5 of the cytosine ring, resulting in 5-methylcytosine (5-mC) (Razin & Riggs 1980) and is a key regulatory mechanism of the genome, playing a central role in diverse...
Incontinence-associated dermatitis (IAD) is a common problem in older people. However, it is frequently misdiagnosed and poorly treated. There is often uncertainty about which product to use to prevent and treat IAD; the different types, brands and how to apply them. This literature review looks specifically at the use of barrier products in the prevention and treatment of IAD. A systematic search found six primary research papers that analysed the effectiveness of various barrier products; they will be compared and contrasted in this review. There is a lack of evidence to recommend any one barrier product over another for use in a standardised skin care protocol such as the regimen suggested by Gray et al (2012). More research needs to be conducted to establish the most effective barrier products on the market. More research is also needed on the efficacy of barrier products in the prevention and treatment solely of IAD rather than combined studies looking at IAD with pressure ulcers.
The purpose of this study was to determine the number of deaths which were caused by choking in a 10 year period in the Irish psychiatric in-patient population and the factors associated with such deaths.
Summary We explore whether the needs of individuals with neurodevelopment disorders have been overlooked during the coronavirus disease 2019 (COVID-19) pandemic and set out the issues that need to be considered in response to future health crises and pandemics.
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