Mortality following Stroke, the Weekend Effect and Related Factors: Record Linkage Study

Increased mortality following hospitalisation for stroke has been reported from many but not all studies that have investigated a 'weekend effect' for stroke. However, it is not known whether the weekend effect is affected by factors including hospital size, season and patient distance from hospital.To assess changes over time in mortality following hospitalisation for stroke and how any increased mortality for admissions on weekends is related to factors including the size of the hospital, seasonal factors and distance from hospital.A population study using person linked inpatient, mortality and primary care data for stroke from 2004 to 2012. The outcome measures were, firstly, mortality at seven days and secondly, mortality at 30 days and one year.Overall mortality for 37 888 people hospitalised following stroke was 11.6% at seven days, 21.4% at 30 days and 37.7% at one year. Mortality at seven and 30 days fell significantly by 1.7% and 3.1% per annum respectively from 2004 to 2012. When compared with week days, mortality at seven days was increased significantly by 19% for admissions on weekends, although the admission rate was 21% lower on weekends. Although not significant, there were indications of increased mortality at seven days for weekend admissions during winter months (31%), in community (81%) rather than large hospitals (8%) and for patients resident furthest from hospital (32% for distances of >20 kilometres). The weekend effect was significantly increased (by 39%) for strokes of 'unspecified' subtype.Mortality following stroke has fallen over time. Mortality was increased for admissions at weekends, when compared with normal week days, but may be influenced by a higher stroke severity threshold for admission on weekends. Other than for unspecified strokes, we found no significant variation in the weekend effect for hospital size, season and distance from hospital

Acceptability, tolerability and safety of the BRIGhTMIND trial: Connectivity-guided intermittent theta-burst stimulation versus F3- repetitive transcranial magnetic stimulation for treatment-resistant depression

\ua9 2024. Background: The BRIGhTMIND study was a double-blind RCT comparing repetitive transcranial magnetic stimulation at a standard simulation site (the “F3” location given by the International 10–20 system, F3-rTMS) versus connectivity-guided intermittent theta burst stimulation (cgiTBS) for treatment-resistant depression. This present study reports the acceptability, safety, and tolerability of F3-rTMS versus cgiTBS. Methods: The present study used quantitative and qualitative methods. Two hundred fifty-four participants were included in the quantitative BRIGhTMIND acceptability and safety analysis (n = 126 F3-rTMS, n = 128 cgiTBS). Qualitative analysis included interviews for 15 participants (n = 7 F3-rTMS, n = 8 cgiTBS) and 582 written comments made by any participant randomised to the BRIGhTMIND trial regarding their experience of TMS and the study. Statistical analyses were used to explore differences between F3-rTMS and cgiTBS, as well as associations between acceptability, impression of change and safety. Qualitative data was analysed using an inductive thematic framework approach. Outcomes: Acceptability, TMS benefits/negative effects and impression of improvement ratings did not differ across the two treatment protocols, with ratings maintained long-term (71.4 % rated TMS acceptable, 48.8 % indicated benefits of TMS outweighed negative effects and 52.2 % feeling somewhat or much better at 26 week follow-up n = 203). Impression of improvement was positively associated with acceptability and TMS benefits. Qualitative themes included participants\u27 TMS experience, TMS response variability, and lay theories of effectiveness. Safety profiles were comparable between F3-rTMS and cgiTBS, with 74.5 % of participants (n = 190/254) experiencing at least one adverse event possibly, probably, or definitely related to TMS. The majority of adverse events were transient and mild, with a sizeable number requiring simple treatments or small adjustments to TMS intensity and coil positioning. The F3-rTMS group had a significantly greater proportion of participants that required small adjustments to TMS to tolerate treatment compared to the cgiTBS group. Serious adverse events were rare, with one serious event in each treatment arm possibly related to TMS (F3-rTMS- psychotic episode, cgiTBS-manic episode). Conclusion: F3-rTMS and cgiTBS are comparably safe, tolerable and highly acceptable interventions for treatment-resistant depression. BRIGhTMIND systematically collected data from a large sample, providing evidence to meet the information needs of patients, clinicians and policy makers

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Dutch women with a low birth weight have an increased risk of myocardial infarction later in life: a case control study

BACKGROUND: To investigate whether low birth weight increases the risk of myocardial infarction later in life in women. METHODS: Nationwide population-based case-control study. Patients and controls: 152 patients with a first myocardial infarction before the age of 50 years in the Netherlands. 568 control women who had not had a myocardial infarction stratified for age, calendar year of the index event, and area of residence. RESULTS: Birth weight in the patient group was significantly lower than in control women (3214 vs. 3370 gram, mean difference -156.3 gram (95%CI -9.5 to -303.1). The odds ratio for myocardial infarction, associated with a birth weight lower than 3000 gram (20(th )percentile in controls) compared to higher than 3000 gram was 1.7 (95%CI 1.1–2.7), while the odds ratio for myocardial infarction for children with a low birth weight (< 2000 g) compared to a birth weight ≥ 2000 g was 2.4 (95%CI 1.0 – 5.8). Both figures did not change after adjustment for putative confounders (age, education level, body mass index, waist-hip ratio, hypertension, diabetes, hypercholesterolemia, smoking, and family history of cardiovascular disease). CONCLUSIONS: Low birth weight is associated with an increased risk of myocardial infarction before age of 50 in Dutch women

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

<p>Abstract</p> <p>Background</p> <p>The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.</p> <p>Methods</p> <p>Hydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.</p> <p>Results</p> <p>Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.</p> <p>Conclusions</p> <p>AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.</p

Snapshot of the Eukaryotic Gene Expression in Muskoxen Rumen—A Metatranscriptomic Approach

BACKGROUND: Herbivores rely on digestive tract lignocellulolytic microorganisms, including bacteria, fungi and protozoa, to derive energy and carbon from plant cell wall polysaccharides. Culture independent metagenomic studies have been used to reveal the genetic content of the bacterial species within gut microbiomes. However, the nature of the genes encoded by eukaryotic protozoa and fungi within these environments has not been explored using metagenomic or metatranscriptomic approaches. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a metatranscriptomic approach was used to investigate the functional diversity of the eukaryotic microorganisms within the rumen of muskoxen (Ovibos moschatus), with a focus on plant cell wall degrading enzymes. Polyadenylated RNA (mRNA) was sequenced on the Illumina Genome Analyzer II system and 2.8 gigabases of sequences were obtained and 59129 contigs assembled. Plant cell wall degrading enzyme modules including glycoside hydrolases, carbohydrate esterases and polysaccharide lyases were identified from over 2500 contigs. These included a number of glycoside hydrolase family 6 (GH6), GH48 and swollenin modules, which have rarely been described in previous gut metagenomic studies. CONCLUSIONS/SIGNIFICANCE: The muskoxen rumen metatranscriptome demonstrates a much higher percentage of cellulase enzyme discovery and an 8.7x higher rate of total carbohydrate active enzyme discovery per gigabase of sequence than previous rumen metagenomes. This study provides a snapshot of eukaryotic gene expression in the muskoxen rumen, and identifies a number of candidate genes coding for potentially valuable lignocellulolytic enzymes

Cardiac tumours in children

Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT) and Magnetic Resonance Imaging (MRI) of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor

Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae

Background: Streptococcus pneumoniae is a common colonizer of the human nasopharynx and one of the major pathogens causing invasive disease worldwide. Dissection of the molecular pathways responsible for colonization, invasion, and evasion of the immune system will provide new targets for antimicrobial or vaccine therapies for this common pathogen. Methodology/Principal Findings: We have constructed mutants lacking the pneumococcal cell wall hydrolases (CWHs) LytB and LytC to investigate the role of these proteins in different phases of the pneumococcal pathogenesis. Our results show that LytB and LytC are involved in the attachment of S. pneumoniae to human nasopharyngeal cells both in vitro and in vivo. The interaction of both proteins with phagocytic cells demonstrated that LytB and LytC act in concert avoiding pneumococcal phagocytosis mediated by neutrophils and alveolar macrophages. Furthermore, C3b deposition was increased on the lytC mutant confirming that LytC is involved in complement evasion. As a result, the lytC mutant showed a reduced ability to successfully cause pneumococcal pneumonia and sepsis. Bacterial mutants lacking both LytB and LytC showed a dramatically impaired attachment to nasopharyngeal cells as well as a marked degree of attenuation in a mouse model of colonization. In addition, C3b deposition and phagocytosis was more efficient for the double lytB lytC mutant and its virulence was greatly impaired in both systemic and pulmonary models of infection. Conclusions/Significance: This study confirms that the CWHs LytB and LytC of S. pneumoniae are essential virulence factor