Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the ‘first wave’ of patients with Covid-19 at Royal ...Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57–82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57–2.27), hypertension (OR 1.72, 95% CI 1.10–2.70), cancer (OR 2.20, 95% CI 1.27–3.81), platelets <150 × 103/μl (OR 1.93, 95% CI 1.13–3.30), C-reactive protein ≥100 μg/ml (OR 1.68, 95% CI 1.05–2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16–3.77) and AKI (OR 2.60, 95% CI 1.64–4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.
BACKGROUND The prevalence of childhood asthma is increasing but few studies have investigated trends in asthma severity. We investigated trends in asthma diagnosis and symptom morbidity between an ...eight year time period in a paired prevalence study. METHODS All children in one single school year aged 8–9 years in the city of Sheffield were given a parent respondent questionnaire in 1991 and 1999 based on questions from the International Survey of Asthma and Allergy in Children (ISAAC). Data were obtained regarding the prevalence of asthma and wheeze and current (12 month) prevalences of wheeze attacks, speech limiting wheeze, nocturnal cough and wheeze, and exertional symptoms. RESULTS The response rates in 1991 and 1999 were 4580/5321 (85.3%) and 5011/6021 (83.2%), respectively. There were significant increases between the two surveys in the prevalence of asthma ever (19.9%v 29.7%, mean difference 11.9%, 95% confidence interval (CI) 10.16 to 13.57, p<0.001), current asthma (10.3% v 13.0%, mean difference 2.7%, 95% CI 1.44 to 4.03, p<0.001), wheeze ever (30.3%v 35.8%, mean difference 5.7%, 95% CI 3.76 to 7.56, p<0.001), wheeze in the previous 12 months (17.0%v 19.4%, mean difference 2.5, 95% CI 0.95 to 4.07, p<0.01), and reporting of medication use (16.9%v 20%, mean difference 3.0%, 95% CI 1.46 to 4.62, p<0.001). There were also significant increases in reported hayfever and eczema diagnoses. CONCLUSIONS Diagnostic labelling of asthma and lifetime prevalence of wheeze has increased. The current 12 month point prevalence of wheeze has increased but this is confined to occasional symptoms. The increased medication rate may be responsible for the static prevalence of severe asthma symptoms. The significant proportion of children receiving medication but reporting no asthma symptoms identified from our 1999 survey suggests that some children are being inappropriately treated or overtreated.
Background: The prevalence and severity of asthma is believed to increase with increasing socioeconomic deprivation. The relationship between asthma diagnosis, symptoms, diagnostic accuracy, and ...socioeconomic deprivation as determined by Townsend scores was determined in Sheffield schoolchildren. Methods: All 6021 schoolchildren aged 8–9 years in one school year in Sheffield were given a parent respondent survey based on International Survey of Asthma and Allergies in Childhood (ISAAC) questions. Results: 5011/6021 (83.2%) questionnaires were returned. Postcode data were available in 4131 replies (82.4%) and were used to assign a composite deprivation score (Townsend score). Scores were divided into five quintiles, with group 1 being least and group 5 being most deprived. A positive trend was observed from group 1 to group 5 for the prevalence of wheeze in the previous 12 months, wheeze attacks ≥4/year, nocturnal wheeze and cough (all p<0.001), cough and/or wheeze “most times” with exertion (p<0.03), current asthma (p<0.001), and significant asthma symptoms (p<0.001). No significant trend was observed for lifetime wheeze or attacks of speech limiting wheeze. There were no significant trends in the prevalence of current asthmatic children without significant symptoms (overdiagnosis) or children with significant asthma symptoms but no current asthma diagnosis (underdiagnosis) across the social groups. There was a significant negative trend in the ratio of asthma medication to asthma diagnosis from least to most deprived groups (p<0.001). Conclusions: Asthma morbidity and severity increase according to the level of socioeconomic deprivation. This may be due to differences in environment, asthma management, and/or symptom reporting. Diagnostic accuracy does not vary significantly across deprivation groups but children living in areas of least deprivation and taking asthma medication are less likely to be labelled as having asthma, suggesting diagnostic labelling bias.
Background: Hypoxia‐inducible factor (HIF)‐1 is a key transcription factor responding to hypoxia. It is composed of an oxygen‐sensitive α subunit (HIF‐1α) and a constitutively expressed β subunit. ...Increasing evidence indicates an essential role for HIF‐1α in infection and immunity. Because inflamed periodontium is thought to be hypoxic, we hypothesize that HIF‐1α is expressed and related to its upstream regulator tumor necrosis factor (TNF)‐α and downstream effecter vascular endothelial growth factor (VEGF).
Methods: Human gingival biopsies were collected from advanced periodontitis sites and clinically healthy sites, and immunohistochemically examined for HIF‐1α and VEGF peptides. The messenger ribonucleic acid (mRNA) and protein levels of HIF‐1α, VEGF, and TNF‐α in the biopsies were then assessed by reverse transcription polymerase chain reaction and Western blotting.
Results: HIF‐1α–positive immunoreactivity was detected in the nuclei of epithelial and endothelial cells. In periodontal pockets, there was a marked increase in the proportion of fibroblast‐like cells and leukocyte‐like cells expressing HIF‐1α. Protein levels of HIF‐1α, VEGF, and TNF‐α were significantly higher in periodontal pockets than in control gingival samples. The mRNA expression of VEGF and TNF‐α was also increased in periodontal pockets.
Conclusion: HIF‐1α is expressed in healthy and diseased periodontium and may be related to TNF‐α and VEGF function during periodontitis.
Aim： To investigate the effects of the cardiotonic steroid, ouabain, on cardiac differentiation of murine embyronic stem cells （mESCs）. Methods： Cardiac differentiation of murine ESCs was enhanced by ...standard hanging drop method in the presence of ouabain （20 pmol/L） for 7 d. The dissociated ES derived cardiomyocytes were examined by flow cytometry, RT-PCR and confocal calcium imaging. Results： Compared with control, mESCs treated with ouabain （20 pmol/L） yielded a significantly higher percentage of cardiomyocytes, and significantly increased expression of a panel of cardiac markers including Nkx 2.5, α-MHC, and β-MHC. The α1 and 2- isoforms Na^＋/K^＋-ATPase, on which ouabain acted, were also increased in mESCs during differentiation. Among the three MAPKs involved in the cardiac hypertrophy pathway, ouabain enhanced ERK1/2 activation. Blockage of the Erkl/2 pathway by U0126 （10 pmol/L） inhibited cardiac differentiation while ouabain （20 pmol/L） rescued the effect. Interestingly, the expression of calcium handling proteins, including ryanodine receptor （RyR2） and sacroplasmic recticulum Ca^2＋ ATPase （SERCA2a） was also upregulated in ouabain-treated mESCs. ESC-derived cardiomyocyes （CM） treated with ouabain appeared to have more mature calcium handling. As demonstrated by confocal Ca^2＋ imaging, cardiomyocytes isolated from ouabain-treated mESCs exhibited higher maximum upstroke velocity （P〈0.01） and maximum decay velocity （P〈0.05）, as well as a higher amplitude of caffeine induced Ca^2＋ transient （P〈0.05）, suggesting more mature sarcoplasmic reticulum （SR）. Conclusion： Ouabain induces cardiac differentiation and maturation of mESC-derived cardiomyocytes via activation of Erk1/2 and more mature SR for calcium handling.
Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms involved are not fully understood. We hypothesized that caveolin‐1 (cav‐1), a plasma membrane signal molecule, might play a ...role in protecting neuroblastoma cells from oxidative injury by modulating nitric oxide (NO) production. We investigated the alterations of cav‐1, cav‐2, nitric oxide synthases (NOS), and NO levels in human SK‐N‐MC neuroblastoma cells exposed to hypoxia with 2% O2. The major discoveries include: (i) cav‐1 but not cav‐2 was up‐regulated in the cells exposed to 15 h of hypoxia; (ii) NO donor 1‐N, N‐di‐(2‐aminoethyl) amino diazen‐1‐ium‐1, 2‐diolate up‐regulated the expression of cav‐1, whereas the non‐selective NOS inhibitor NG‐nitro‐l‐arginine methyl ester and inducible NOS (iNOS) inhibitor 1400W each abolished the increase in cav‐1 expression in the hypoxic SK‐N‐MC cells. These results suggest that iNOS‐induced NO production contributes to the up‐regulation of cav‐1 in the hypoxic SK‐N‐MC cells. Furthermore, we studied the roles played by cav‐1 in regulating NO, NOS, and apoptotic cell death in the SK‐N‐MC cells subjected to 15 h of hypoxic treatment. Both cav‐1 transfection and cav‐1 scaffolding domain peptide abolished the induction of iNOS, reduced the production of NO, and reduced the rates of apoptotic cell death in the hypoxic SK‐N‐MC cells. These results suggest that increased expression of cav‐1 in response to hypoxic stimulation could prevent oxidative injury induced by reactive oxygen species. The interactions of cav‐1, NO, and NOS could be an important signal pathway in protecting the neuroblastoma cells from oxidative injury, contributing to the hypoxic tolerance of neuroblastoma cells.
Paralytic rabies after a two week holiday in India SOLOMON, Tom; MARSTON, Denise; FOOKS, Anthony R ...
BMJ. British medical journal (International ed.),
2005, Letnik:
331, Številka:
7515
Journal Article
PDF
