666 research outputs found
A Bivariate Genome-Wide Approach to Metabolic Syndrome STAMPEED Consortium
No full textOBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
No full textSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be
associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose
polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p,0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03– 1.16), p = 2.761023) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03–1.21,
p = 4.861023). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/ 2 mutation carriers and should be more comprehensively studied
Trends in alcohol withdrawal management by medical toxicologists in the acute care setting: an analysis of the Toxicology Investigators Consortium (ToxIC) Core Registry, 2016-2022.
No full textAIMS: Alcohol withdrawal syndrome (AWS) requires urgent treatment to prevent morbidity and mortality. In the acute care setting, medical toxicologists play a critical role in AWS management, including the use of gamma-aminobutyric acid agonists and adjunctive medications. We aim to introduce the addiction medicine community to this role by describing clinical presentation and treatment of patients with AWS in the Toxicology Investigators Consortium Core Registry.
METHODS: Medical toxicologists from participating sites enter demographic, exposure, clinical presentation, and treatment data on all patients they evaluate into the Core Registry. This was a secondary analysis of registry patients evaluated for AWS from 2016 to 2022. Data were coded in a spreadsheet and analyzed using descriptive statistics.
RESULTS: We included 1093 cases. Agitation and delirium/toxic psychosis were documented in 373 (34.1%) and 227 (20.8%) patients, respectively. Benzodiazepines were the most common gamma-aminobutyric acid agonist treatment (n = 539, 49.3%). There was an overall decrease in the use of benzodiazepines alone and increases in the use of phenobarbital, ketamine, and dexmedetomidine. Intubation was performed in 115 (10.5%) patients. Naltrexone, used for alcohol use disorder, was given in 88 (8.1%) cases. The absolute number of AWS cases increased during this period.
CONCLUSIONS: Use of benzodiazepines alone to manage AWS decreased while phenobarbital, ketamine, and dexmedetomidine use increased. Many patients had severe withdrawal manifestations, and some received alcohol use disorder treatment, suggesting that medical toxicologists see more severe cases in the acute care setting and have an opportunity to address the underlying use disorder
Genome-wide association study identifies eight loci associated with blood pressure
No full textElevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and <i>in silico</i> comparison (CHARGE consortium, N= 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10<sup>−24</sup>), CYP1A2 (P = 1 × 10<sup>−23</sup>), FGF5 (P = 1 × 10<sup>−21</sup>), SH2B3 (P = 3 × 10<sup>−18</sup>), MTHFR (P = 2 × 10<sup>−13</sup>), c10orf107 (P = 1 × 10<sup>−9</sup>), ZNF652(P = 5 × 10<sup>−9</sup>) and PLCD3 (P = 1 × 10<sup>−8</sup>) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease
Neurodevelopmental Disorders and Risk of Concussion: Findings from the National Collegiate Athletic Association Department of Defense Grand Alliance Concussion Assessment, Research, and Education (NCAA-DOD CARE) Consortium (2014-2017)
No full textEvidence suggests neurodevelopmental disorders (NDs) may be associated with an increased incidence of concussion, but no studies have cross-sectionally and longitudinally assessed the associations of NDs and sex with concussion in collegiate athletes. We sought to assess the odds and relative risk (RR) of concussion in athletes self-reporting a diagnosis of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), and ADHD+LD. Data from the Concussion Assessment, Research and Education (CARE) Consortium (2014-2017) were used to evaluate the likelihood of concussion for male and female athletes with ADHD, LD, and ADHD+LD, relative to controls. Odds ratios (ORs) of concussion history prior to enrollment and relative risk ratios for incurring a concussion following enrollment, with and without concussion history were calculated for all groups. Athletes with self-reported diagnosis of ADHD, LD, and ADHD+LD were more likely to report a single concussion (OR range = 1.528 to 1.828) and multiple concussions (OR range = 1.849 to 2.365) prior to enrollment in the CARE Consortium, irrespective of sex compared with control athletes. While enrolled in CARE, male athletes with ADHD, LD, and ADHD+LD had greater risk of incurring a concussion (RR range = 1.369 to 2.243) than controls, irrespective of concussion history. Male athletes with ADHD+LD with concussion history (RR = 2.221) and without concussion history (RR = 1.835) had greater risk of incurring a concussion than controls. These results suggest NDs may be associated with increased odds of single and multiple concussions, irrespective of sex. However, when we accounted for concussion history, it appears only male athletes with ADHD+LD had greater risk than respective controls. There were no significant differences between females and males with ADHD, LD, or ADHD+LD for either odds of concussion history or risk for incurring concussion
The added value of ordinal analysis in clinical trials: an example in traumatic brain injury.
No full textINTRODUCTION: In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial. METHODS: We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics. RESULTS: Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively. CONCLUSIONS: Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects
Early Program Evaluation of the Impact of ELNEC Communication Education on Registered Nurse Death Anxiety and Communication Apprehension Scores
No full textNurse expertise with end-of-life (EOL) conversation skills can facilitate the assessment of the patient’s sociocultural and spiritual beliefs about quality of life issues, yet nurse death anxiety may act as a barrier to needed conversations. Nurses are the most consistent healthcare provider at the inpatient bedside and as such they play an important role in EOL conversations.
The purpose of this practice dissertation project was to evaluate the impact of a nurse-facilitator led quality improvement initiative in one acute care hospital using the End of Life Nursing Education Consortium (ELNEC) communication Module 6. Specifically, nurse attitudes regarding death anxiety (using the Revised Death Anxiety Scale [DAS-R]) and communication apprehension (using the Communication Apprehension with Dying [CA-Dying] scale) were evaluated pre and post education. A multi-faceted evaluation approach was utilized, the Promoting Action on Research Implementation in Health Services (PARiHS) framework for assessment of organizational readiness for change, and the Donabedian Quality Model to evaluate efficacy of the ELNEC Module 6 education on nurse death anxiety and communication apprehension.
Preliminary evaluation of the ELNEC Module 6 intervention indicated that, controlling for the DAS-R pre-score, nurses with an ADN or Diploma degree had a significantly lower post-test death anxiety score than nurses with a BSN or MSN degree. Nurses who cared for more dying patients per year, controlling for the CA-Dying prescore, had a statistically significant lower CA-Dying score. Experiential learning and reflection are central to creating a culture of innovation, improvement and effectiveness.
The ELNEC curriculum promotes personal reflection about death. By embedding nurses skilled in advanced communication techniques at the frontline, a sustainable model for peer consultation and support regarding difficult conversations is possible. Providing effective palliative care across an organization is a complex endeavor. A doctorally prepared nurse can have an integral role in transforming EOL care
Recommended from our members
Recovery Profiles after Concussion among Male Student-Athletes and Service Cadets with a Family History of Neurodegenerative Disease: Data from the NCAA-DoD CARE Consortium
No full textPreliminary evidence indicates that genetic factors associated with having a family history of neurodegenerative disease (fhNDD) may predispose an individual to persistent symptoms and poorer cognitive performance after concussion. No previous study, however, longitudinally examined athletes with (+) and without (-) a fhNDD. Therefore, we aimed to compare clinical symptoms and cognitive performance of fhNDD+ and fhNDD- athletes at baseline and at multiple time points after concussion. Questionnaire data from the Concussion Assessment, Research and Education (CARE) Consortium were used to identify male athletes and cadets with (n = 51) and without (n = 102) a fhNDD (Alzheimer disease, Parkinson disease, mild cognitive impairment, and non-Alzheimer dementia). All athletes completed the SCAT3 symptom checklist and ImPACT test before their sport season and again within 24-48 h of injury, at the unrestricted return-to-play, and at six months post-concussion. Compared with fhNDD-, fhNDD+ individuals demonstrated greater decrements in visual memory (relative to baseline) 24-48 h post-injury (p < 0.05, d = 0.18). In addition, a main effect of group was observed for impulse control. Compared with fhNDD- athletes, fhNDD+ individuals demonstrated greater decrements in impulse control, 24-48 h post-injury, at the return to play, and at six-month assessments (p < 0.01, d = 0.23). These findings suggest that male athletes with a fhNDD may exhibit greater decrements in cognitive performance after concussion. Small, subtle deficits in cognitive performance may still significantly hinder day-to-day function in student-athletes
Impact of renin–angiotensin–aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study
No full textBackground
The influence of renin–angiotensin–aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients.
Methods
Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission.
Results
A total of 737 patients were included—538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58–0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7–22.8 days) in ICU and 6.7 days (5.9–7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1–18.6 days) and 6.4 days (5.1–7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge.
Conclusions
In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay.
Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932
Design and rationale of the COVID-19 Critical Care Consortium international, multicentre, observational study
No full textIntroduction There is a paucity of data that can be used to guide the management of critically ill patients with COVID-19. In response, a research and data-sharing collaborative—The COVID-19 Critical Care Consortium—has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights crucial to improving outcomes.Methods and analysis This is an international, multicentre, observational study of patients with confirmed or suspected SARS-CoV-2 infection admitted to ICUs. This is an evolving, open-ended study that commenced on 1 January 2020 and currently includes >350 sites in over 48 countries. The study enrols patients at the time of ICU admission and follows them to the time of death, hospital discharge or 28 days post-ICU admission, whichever occurs last. Key data, collected via an electronic case report form devised in collaboration with the International Severe Acute Respiratory and Emerging Infection Consortium/Short Period Incidence Study of Severe Acute Respiratory Illness networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane oxygenation and associated complications, as well as data on adjunctive therapies.Ethics and dissemination Local principal investigators will ensure that the study adheres to all relevant national regulations, and that the necessary approvals are in place before a site may contribute data. In jurisdictions where a waiver of consent is deemed insufficient, prospective, representative or retrospective consent will be obtained, as appropriate. A web-based dashboard has been developed to provide relevant data and descriptive statistics to international collaborators in real-time. It is anticipated that, following study completion, all de-identified data will be made open access.Trial registration number ACTRN12620000421932 (http://anzctr.org.au/ACTRN12620000421932.aspx)
- …
