Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA1c and other predictors of increasing BMISDS.

BACKGROUND: Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. METHODS: Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A1c (HbA1c ), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. RESULTS: Totally, 11 025 children (48% females) (30 994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA1c , 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA1c and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P < .001). CONCLUSION: Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA1c , long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA1c.

Impact of body mass index on risk of acute kidney injury and mortality in elderly patients undergoing hip fracture surgery.

The literature is limited regarding risk factors for acute kidney injury (AKI) and mortality in hip fracture patients, although AKI is common in these patients. While obese patients were at increased risk of AKI, underweight patients with and without AKI had elevated mortality for up to 1 year after hip fracture surgery, compared with normal-weight patients. INTRODUCTION: This study aimed to examine risk of postoperative AKI and subsequent mortality, by body mass index (BMI) level, in hip fracture surgery patients aged 65 and over. METHODS: A regional cohort study using medical databases was used. We included all patients who underwent surgery to repair a hip fracture during the years 2005-2011 (n = 13,529) at hospitals in Northern Denmark. We calculated cumulative risk of AKI by BMI level during 5 days postsurgery and subsequent short-term (6-30 days postsurgery) and long-term (31-365 days post-surgery) mortality. We calculated crude and adjusted hazard ratios (aHRs) for AKI and death with 95% confidence intervals (CIs), comparing underweight, overweight, and obese patients with normal-weight patients. RESULTS: Risks of AKI within five postoperative days were 11.9, 10.1, 12.5, and 17.9% for normal-weight, underweight, overweight, and obese patients, respectively. Among those who developed AKI, short-term mortality was 14.1% for normal-weight patients compared to 23.1% for underweight (aHR 1.7 (95% CI 1.2-2.4)), 10.7% for overweight (aHR 0.9 (95% CI 0.6-1.1)), and 15.2% for obese (aHR 0.9 (95% CI 0.6-1.4)) patients. Long-term mortality was 24.5% for normal-weight, 43.8% for underweight (aHR 1.6 (95% CI 1.0-2.6)), 20.5% for overweight (aHR 0.8 (95% CI 0.6-1.2)), and 21.4% for obese (aHR 1.1 (95% CI 0.7-1.8) AKI patients. Similar associations between BMI and mortality were observed among patients without postoperative AKI, although the absolute mortality risk estimates by BMI were considerably lower in patients without than in those with AKI. CONCLUSIONS: Obese patients were at increased risk of AKI compared with normal-weight patients. Among patients with and without postoperative AKI, overweight and obesity were not associated with mortality. Compared to normal-weight patients, underweight patients had elevated mortality for up to 1 year after hip fracture surgery irrespective of the presence of AKI. The absolute mortality risks were higher in all BMI groups with the presence of AKI.

Risk of acute renal failure and mortality after surgery for a fracture of the hip: a population-based cohort study.

AIMS: We examined risk of developing acute renal failure and the associated mortality among patients aged > 65 years undergoing surgery for a fracture of the hip. PATIENTS AND METHODS: We used medical databases to identify patients who underwent surgical treatment for a fracture of the hip in Northern Denmark between 2005 and 2011. Acute renal failure was classified as stage 1, 2 and 3 according to the Kidney Disease Improving Global Outcome criteria. We computed the risk of developing acute renal failure within five days after surgery with death as a competing risk, and the short-term (six to 30 days post-operatively) and long-term mortality (31 days to 365 days post-operatively). We calculated adjusted hazard ratios (HRs) for death with 95% confidence intervals (CIs). RESULTS: Among 13 529 patients who sustained a fracture of the hip, 1717 (12.7%) developed acute renal failure post-operatively, including 1218 (9.0%) with stage 1, 364 (2.7%) with stage 2, and 135 (1.0%) with stage 3 renal failure. The short-term mortality was 15.9% and 5.6% for patients with and without acute renal failure, respectively (HR 2.8, 95% CI 2.4 to 3.2). The long-term mortality was 25.0% and 18.3% for those with and without acute renal failure, respectively (HR 1.3, 95% CI 1.2 to 1.5). The mortality was higher in patients with an increased severity of renal failure. CONCLUSION: Acute renal failure is a common complication of surgery in elderly patients who sustain a fracture of the hip, and is associated with increased mortality up to one year after surgery despite adjustment for coexisting comorbidity and medication before surgery. Cite this article: Bone Joint J 2016;98-B:1112-18.

Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study.

BACKGROUND/OBJECTIVE: Prenatal exposure to antibacterials may permanently dysregulate fetal metabolic patterns via epigenetic pathways or by altering maternal microbiota. We examined the association of prenatal exposure to systemic antibacterials with overweight and obesity in schoolchildren. SUBJECTS/METHODS: We conducted a prevalence study among Danish schoolchildren aged 7-16 years using data from routine school anthropometric evaluations conducted during 2002-2013. Prenatal exposure to antibacterials was ascertained by using maternal prescription dispensations and infection-related hospital admissions during pregnancy. We defined overweight and obesity among the children using standard age- and sex-specific cutoffs. We computed sex-specific adjusted prevalence ratios (aPRs) of overweight and obesity associated with exposure to prenatal antibacterials, adjusting for maternal age at delivery, marital status, smoking in pregnancy and multiple gestation; we also stratified the analyses by birth weight. RESULTS: Among 9886 schoolchildren, 3280 (33%) had prenatal exposure to antibacterials. aPRs associated with the exposure were 1.26 (95% confidence interval (CI): 1.10-1.45) for overweight and 1.29 (95% CI: 1.03-1.62) for obesity. Among girls, aPRs were 1.16 (95% CI: 0.95-1.42) for overweight and 1.27 (95% CI: 0.89 to 1.82) for obesity. Among boys, aPRs were 1.37 (95% CI: 1.13-1.66) for overweight and 1.29 (95% CI: 0.96-1.73) for obesity. The aPR for overweight was higher among schoolchildren with birth weight <3500 g (aPR: 1.30, 95% CI: 1.05-1.61) than in schoolchildren with birth weight ⩾3500 g (aPR: 1.18, 95% CI: 0.95-1.46). Inversely, the association for obesity was higher among schoolchildren with birth weight ⩾3500 g (aPR: 1.35, 95% CI: 1.00-1.81) than among those who were <3500 g at birth (aPR: 1.16, 95% CI: 0.82-1.65). CONCLUSIONS: Prenatal exposure to systemic antibacterials is associated with an increased risk of overweight and obesity at school age, and this association varies by birth weight.

Approaches for improving image quality in magnetic induction tomography.

Magnetic induction tomography (MIT) is a contactless and non-invasive method for imaging the passive electrical properties of objects. Measuring the weak signal produced by eddy currents within biological soft tissues can be challenging in the presence of noise and the large signals resulting from the direct excitation-detection coil coupling. To detect haemorrhagic stroke in the brain, for instance, high measurement accuracy is required to enable images with enough contrast to differentiate between normal and haemorrhaged brain tissues. The reconstructed images are often very sensitive to inevitable measurement noise from the environment, system instabilities and patient-related artefacts such as movement and sweating. We propose methods for mitigating signal noise and improving image reconstruction. We evaluated and compared the use of a range wavelet transforms for signal denoising. Adaptive regularization methods including L-curve, generalized cross validation (GCV) and noise estimation were also compared. We evaluated all these described methods with measurements of in vitro tissues resembling a peripheral haemorrhagic cerebral stroke created by placing a bio-membrane package filled with 10 ml blood in a swine brain of 100 ml. We show that wavelet packet denoising combined with adaptive regularization can improve the quality of reconstructed images.