Nord-Trøndelag Hospital Trust

About: Nord-Trøndelag Hospital Trust is a based out in . It is known for research contribution in the topics: Population & Hazard ratio. The organization has 119 authors who have published 275 publications receiving 3939 citations.

Biobank-driven genomic discovery yields new insight into atrial fibrillation biology

Abstract: To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)1, or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an 'atrial cardiomyopathy'2, either during fetal heart development or as a response to stress in the adult heart.

Subclinical thyroid dysfunction and fracture risk: A meta-analysis

Abstract: Importance Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. Objective To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. Data Sources and Study Selection The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Data Extraction Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH Main Outcome and Measures The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Results Among 70 298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21 722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. Conclusions and Relevance Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mortality – a prospective study of patients admitted with infection to the emergency department

Abstract: We aimed to evaluate the clinical usefulness of qSOFA as a risk stratification tool for patients admitted with infection compared to traditional SIRS criteria or our triage system; the Rapid Emergency Triage and Treatment System (RETTS). The study was an observational cohort study performed at one Emergency Department (ED) in an urban university teaching hospital in Norway, with approximately 20,000 visits per year. All patients >16 years presenting with symptoms or clinical signs suggesting an infection (n = 1535) were prospectively included in the study from January 1 to December 31, 2012. At arrival in the ED, vital signs were recorded and all patients were triaged according to RETTS vital signs, presenting infection, and sepsis symptoms. These admission data were also used to calculate qSOFA and SIRS. Treatment outcome was later retrieved from the patients’ electronic records (EPR) and mortality data from the Norwegian population registry. Of the 1535 admitted patients, 108 (7.0%) fulfilled the Sepsis2 criteria for severe sepsis. The qSOFA score ≥2 identified only 33 (sensitivity 0.32, specificity 0.98) of the patients with severe sepsis, whilst the RETTS-alert ≥ orange identified 92 patients (sensitivity 0.85, specificity 0.55). Twenty-six patients died within 7 days of admission; four (15.4%) of them had a qSOFA ≥2, and 16 (61.5%) had RETTS ≥ orange alert. Of the 68 patients that died within 30 days, only eight (11.9%) scored ≥2 on the qSOFA, and 45 (66.1%) had a RETTS ≥ orange alert. In order to achieve timely treatment for sepsis, a sensitive screening tool is more important than a specific one. Our study is the fourth study were qSOFA finds few of the sepsis cases in prehospital or at arrival to the ED. We add information on the RETTS triage system, the two highest acuity levels together had a high sensitivity (85%) for identifying sepsis at arrival to the ED - and thus, RETTS should not be replaced by qSOFA as a screening and trigger tool for sepsis at arrival. In this observational cohort study, qSOFA failed to identify two thirds of the patients admitted to an ED with severe sepsis. Further, qSOFA failed to be a risk stratification tool as the sensitivity to predict 7-day and 30-day mortality was low. The sensitivity was poorer than the other warning scores already in use at the study site, RETTS-triage and the SIRS criteria.

Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma

Abstract: PurposeThe aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).MethodsWe performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.ResultsTwenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significant...

Anti-Mullerian hormone in the diagnosis of polycystic ovary syndrome: can morphologic description be replaced?

Abstract: Study question Can anti-Mullerian hormone (AMH) level replace the morphologic description in the diagnosis of polycystic ovary syndrome (PCOS) and what is the relationship between AMH and different diagnostic criteria of PCOS? Summary answer AMH may be a good substitute for polycystic ovarian morphology (PCOM) in diagnosing PCOS. What is known already AMH has been suggested as an alternative to antral follicle count (AFC) in diagnosing PCOS. Cut-off values for AMH studied so far show an acceptable specificity but a rather poor sensitivity, leaving up to one-third of PCOS women undiagnosed. Study design, size, duration We used data from a cross-sectional, case-control study on women with prior preterm birth and their controls, i.e. women with prior full-term birth. Among 262 women, 56 met the Rotterdam criteria (PCOS-R) and 44 the Androgen Excess-PCOS Society (PCOS-AES) criteria of PCOS. Participants/materials, setting, methods Fasting blood samples were collected, a transvaginal ultrasound investigation and a clinical examination were performed. PCOS-R and PCOS-AES were re-diagnosed by replacing PCOM with AMH. Main outcome measures were the prevalence of PCOS, PCOM, hirsutism, oligoamenorrhoea and serum levels of AMH and androgens. Main results and the role of chance When replacing PCOM with AMH, the specificity and sensitivity for identifying PCOS were 97.1 and 94.6% according to the PCOS-R criteria and 97.2 and 95.5% according to the PCOS-AES criteria, respectively, at an AMH cut-off value of 20 pmol/l. Limitations, reasons for caution The results need to be confirmed when international standards and methods for AMH measurements are established. Wider implications of the findings AMH may be a good substitute for PCOM in diagnosing PCOS. Study funding/competing interest(s) This study was financed by the Cooperative of Central Norway Regional Health Authority and Norwegian University of Science and Technology. The authors have no interests to disclose. Trial registration number This study is registered at www.clinicaltrials.gov as NCT01355536.