Urinary tract infection caused by ESBL are a serious problem and identifying risk factors facilitates early detection and improved prognosis. Male sex, hospitalisation, institutionalisation, diabetes, recurrent UTI and comorbidity were risk factors and were associated with more symptoms and longer hospital stay.
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).
Reliable reference ranges are important in the interpretation of laboratory data, and it is incumbent on each laboratory to verify that the ranges they use are appropriate for the patient population they serve. The objective of this study was to determine population-specific reference ranges for thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and total triiodothyronine (TT3) on the Abbott ARCHITECT 12000 analyzer. For this study, we used human serum samples collected from a population in Castilla y León, Spain. Serum samples were collected from 304 individuals (male, n = 151; female, n = 153; age 12-94 years) representing outpatients (n=100), hospitalized patients (n = 104) and apparently healthy subjects (n = 100). Individuals taking any medications, with a history of thyroid disorder, or severe non-thyroidal illness were excluded from the study. For healthy subjects, the following reference intervals were determined: TSH, 0.51-5.95 mlU/l; fT4, 0.84-1.42 ng/dl (10.77- 18.21 pmol/l); fT3, 1.48-3.37 pg/ml (2.27-5.18 pmol/l); and TT3, 0.65-1.46 ng/ml (1.00-2.24 nmol/l). In this group, TSH and fT4 showed significant differences between men and women, but fT3 and TT3 did not. Conversely, fT3 and TT3 showed significant age-related differences, but TSH and fT4 did not. Within the outpatient group, no significant differences were seen between men and women for any of the hormones, but age-related differences were significant for fT3 and TT3. Within the hospitalized patient group, significant differences between men and women were found for TSH only, and age-related differences were significant for TSH, fT3 and TT3. Our findings are basically in accordance with previously published results for fT3, TT3 and TSH, but for fT4 our results differ from other data in the literature. This highlights the need for laboratories to confirm that the reference ranges they use are appropriate for the population they serve.
Background: Cannabis is the illicit drug most widely used by young people in high-income countries. Allergy symptoms have only occasionally been reported as one of the adverse health effects of cannabis use. Objectives: To study IgE-mediated response to cannabis in drug users, atopic patients, and healthy controls. Methods: Asthmatic patients sensitised to pollen, and all patients sensitised to tobacco, tomato and latex, considered as cross-reacting allergens, were selected from a data base of 21,582 patients. Drug users attending a drug-rehabilitation clinic were also included. Controls were 200 non-atopic blood donors. Specific IgE determination, prick tests and specific challenge with cannabis extracts were performed in patients and controls. Results: Overall, 340 patients, mean age 26.9 ± 10.7 years, were included. Males (61.4%) were the most sensitised to cannabis (p < 0.001). All cannabis-sensitised patients were alcohol users. Eighteen (72%) of the patients allergic to tomato were sensitised to cannabis, but a positive specific challenge to cannabis was highest in patients sensitised to tobacco (13/21, 61.9%), (p < 0.001). Pollen allergy was not a risk factor for cannabis sensitisation. Prick tests and IgE for cannabis had a good sensitivity (92 and 88.1%, respectively) and specificity (87.1 and 96%) for cannabis sensitisation. Conclusions: Cannabis may be an important allergen in young people. Patients previously sensitised to tobacco or tomato are at risk. Cannabis prick tests and IgE were useful in detecting sensitisation.
Patients with hip fracture, had substantially higher mortality than comparable healthy people, and mortality was highest in the first six months after fracture. Age and prior comorbidities were associated with excess mortality.
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