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Aim: There is a lack of studies on paediatric triage systems. This study aimed to evaluate patient safety of the Gothenburg‐developed paediatric triage system West Coast System for Triage—Paediatric (WEST‐P). Method: This study was performed at the paediatric emergency department in Gothenburg, Sweden, October 2020 to April 2021. Included patients were double‐triaged with the WEST‐P, and the established Rapid Emergency Triage and Treatment System—Paediatrics (RETTS‐p). We compared the level of urgency between both systems to identify potentially undertriaged patients. Also, we assessed the patient safety according to clinical assessment at presentation, and pre‐defined criteria. Results: This study included 2290 (23%) of triaged patients (44% girls, median age: 5.0 years) during the study period. A higher number of patients triaged to low urgency in WEST‐P compared to RETTS‐p (p < 0.0001) was observed, and 497 cases with low WEST‐P and high RETTS‐p urgencies identified. Of these, 29 had a clinical assessment indicating high urgency. After patient safety assessment, seven (0.4%) were determined undertriaged by the new triage system WEST‐P. Conclusion: Our findings demonstrate a low risk of undertriage in the new WEST‐P. Thus, the WEST‐P has a high degree of patient safety when used in a paediatric emergency department. [ABSTRACT FROM AUTHOR]

The amount of research being performed in children, in particular pharmacological research, is lower than in adults, which is in direct contrast to the aims of the UN Convention on the Rights of the Child. A Pediatric Clinical Research Center (PCRC) has been established at Sahlgrenska University Hospital with the aim of supporting clinical research in children and adolescents. The number of inquiries and initiated clinical studies at PCRC has increased since the start in 2016. In addition, there is a need for regional and national infrastructures for paediatric clinical research and a national network for paediatric clinical studies. Conclusion: Sahlgrenska University Hospital has established an infrastructure to support paediatric research and to work with national networks and infrastructures. [ABSTRACT FROM AUTHOR]

Aim: There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden.Methods: A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs for paediatric clinical trials in Sweden. Questions regarding premises, competence, organisation, support for paediatric clinical trials and Good Clinical Practice Training were addressed.Results: In total, 137 individuals responded to the survey (109 doctors and 28 nurses). Overall, 61% of the respondents had previous experience of paediatric clinical trials. Some respondents had access to trial units, but only 34% had used the trial unit for support. Half of the responders were interested in recurrent paediatric Good Clinical Practice training. Doctors responded that clinical work often had to be prioritised and emphasised the need for research time.Conclusion: This study clearly shows the commitment for clinical trials among doctors and nurses involved in paediatric care in Sweden, but also that administrative, logistic and economic support in a sustainable setting and an expanded national collaboration are needed. [ABSTRACT FROM AUTHOR]

Background: Puberty is a critical period for bone mass accrual, and late puberty in boys is associated with reduced bone mass in adult men. The role of variations in pubertal timing within the normal range for adult fracture risk in men is, however, unknown. We, therefore, assessed the association between age at peak height velocity (PHV), an objective measure of pubertal timing, and fracture risk in adult men.Methods and Findings: In the BMI Epidemiology Study Gothenburg, 31,971 Swedish men born between January 1, 1945, and December 31, 1961, with detailed growth data (height and weight) available from centrally archived school healthcare records and the conscription register were followed until December 31, 2016. Age at PHV was calculated according to a modified infancy-childhood-puberty model, and fracture information was retrieved from the Swedish National Patient Register. The mean ± SD age at PHV was 14.1 ± 1.1 years. In total, 5,872 men (18.4%) sustained at least 1 fracture after 20 years of age and 5,731 men (17.9%) sustained a non-vertebral fracture after 20 years of age during a mean ± SD follow-up of 37.3 ± 11.7 years. Cox proportional hazards models adjusted for birth year and country of origin revealed that age at PHV was associated with the risk of any fracture and non-vertebral fracture. Participants with age at PHV in the highest tertile (after 14.5 years of age) were at greater risk of any fracture (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22, P < 0.001) and non-vertebral fracture (HR 1.16, 95% CI 1.09-1.24, P < 0.001) compared with those with age at PHV in the lowest tertile (at 13.6 years of age or younger). Additional adjustments for birthweight, childhood BMI, adult educational level, and young adult height did not attenuate the associations between age at PHV and adult fracture risk. Limitations of this study include the inability to adjust for important risk factors for fracture, inadequate power to assess the relation between pubertal timing and specific fracture types, and the limited generalizability to other populations.Conclusions: In this study, we observed that late pubertal timing was associated with increased adult fracture risk in men. These findings suggest that information on pubertal timing might aid in the identification of those men at greatest risk of fracture. [ABSTRACT FROM AUTHOR]

Aim: Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.Methods: Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3-34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3-30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.Results: The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15-31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman's r = -0.9, p < 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.Conclusion: The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin-breaking procedures. [ABSTRACT FROM AUTHOR]

AIMS Medication reviews by a third party have been introduced as a method to improve drug treatment in older people. We assessed whether this intervention reduces mortality and hospitalization for nursing home residents. METHODS Systematic literature searches were performed (from January 1990 to June 2012) in Medline, EMBASE, Cochrane Library, ProQuest Nursing & Allied Health Sources and Health Technology Assessment databases. We included randomized and nonrandomized controlled trials (RCTs and non-RCTs) of medication reviews compared with standard care or other types of medication reviews in nursing home residents. The outcome variables were mortality and hospitalization. Study quality was assessed systematically. We performed meta-analyses using random-effects models. RESULTS Seven RCTs and five non-RCTs fulfilled the inclusion criteria. The mean age of included patients varied between 78 and 86 years. They were treated with a mean of 4-12 drugs. The study quality was assessed as high (n = 1), moderate (n = 4) or low (n = 7). Eight studies compared medication reviews with standard care. In six of them, pharmacists were involved in the intervention. Meta-analyses of RCTs revealed a risk ratio (RR) for mortality of 1.03 [medication reviews vs. standard care; five trials; 95% confidence interval (CI) 0.85-1.23]. The corresponding RR for hospitalization was 1.07 (two trials; 95% CI 0.61-1.87). CONCLUSIONS Our findings indicate that medication reviews for nursing home residents do not reduce mortality or hospitalization. More research in the setting of controlled trials remains to be done in order to clarify how drug treatment can be optimized for these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how BMI changes during childhood and adolescence predict 'adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous and visceral fat mass by BMI changes during childhood and adolescence. RESEARCH DESIGN AND METHODS--Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study (n = 612). Body composition was analyzed using dual-energy X-ray absorptiometry and adipose tissue areas using abdominal computed tomography at 18 to 20 years of age. RESULTS--The main finding in the present study was that subjects with increases in BMI Z score of more than 1 SD during adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%; P < 0.001) and visceral adipose tissue areas (+91%; P < 0.001) than subjects with unchanged BMI Z-score. In contrast, subjects with increases in BMI Z score of more than 1 SD during late childhood had a larger amount of adult subcutaneous adipose tissue (+83%; P < 0.001) than subjects with unchanged BMI Z score but an unaffected amount of visceral adipose tissue. BMI changes during adolescence predict both visceral and subcutaneous adipose tissue of the abdomen, whereas BMI changes during late childhood predict only the subcutaneous adipose tissue. CONCLUSIONS--The amount of visceral adipose tissue in young adult men was associated with BMI changes specifically during adolescence, whereas the amount of subcutaneous adipose tissue was associated with BMI changes during both late childhood and adolescence. Diabetes 58:867-874, 2009 [ABSTRACT FROM AUTHOR]

The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m²) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18-20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 ± 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI. Diabetes 55:3047-3052, 2006 [ABSTRACT FROM AUTHOR]

Abstract: Mice deficient for all known thyroid hormone receptors, TRα1−/−β−/− mice, display a clear skeletal phenotype characterized by growth retardation, delayed maturation of long bones and decreased trabecular and total bone mineral density (BMD; −14.6 ± 2.8%, −14.4 ± 1.5%). The aim of the present study was to investigate the molecular mechanisms behind the skeletal phenotype in TRα1−/−β−/− mice. Global gene expression analysis was performed on total vertebrae from wild-type (WT) and TRα1−/−β−/− mice using DNA microarray and the results were verified by real-time PCR. The mRNA levels of six genes (AdipoQ, Adipsin, Fat-Specific Protein 27 (FSP 27), lipoprotein lipase (LPL), retinol-binding protein (RBP) and phosphoenolpyruvate carboxykinase (PEPCK)) expressed by mature adipocytes were increased in TRα1−/−β−/− compared with WT mice. An increased amount of fat (225% over WT) due to an increased number but unchanged mean size of adipocytes in the bone marrow of TRα1−/−β−/− mice was revealed. Interestingly, the mRNA levels of the key regulator of osteoclastogenesis, receptor activator of NF-ϰb ligand (RANKL), were dramatically decreased in TRα1−/−β−/− mice. In conclusion, TRα1−/−β−/− mice demonstrated increased expression of adipocyte specific genes and an increased amount of bone marrow fat. Thus, these mice have increased adipogenesis in bone marrow associated with decreased trabecular bone mineral density (BMD). One may speculate that these effects either could be caused by an imbalance in the differentiation of the osteoblast and the adipocyte lineages at the expense of osteoblastogenesis, or by independent effects on the regulation of both osteoblastogenesis and adipogenesis. [Copyright &y& Elsevier]

Aim: Clinical trials and the need for new treatments were recently listed among the most important factors for child health. The aim of the present study was to describe some of our experiences with budget preparations in paediatric clinical trials. Methods: We selected 10 trials sponsored by the pharmaceutical industry at the Pediatric Clinical Research Center at Sahlgrenska University Hospital in Gothenburg, Sweden. We compared the sponsor's initial budget (budget proposal from the sponsor), with the final budget (negotiated and agreed between sponsor and site) and identified areas where discrepancies may arise. Results: The mean difference in total budget amount between the initial budget and the final budget was +60% (mean 59%, range 31%–139%). The costs for preparation of the clinical trial, time spent for study activities and costs for examinations were identified as key budget items for these differences. Conclusion: Our findings indicate that a substantial part of the trial‐related costs would not be covered by the sponsor, had the initial budget been accepted. A thorough review and budget negotiation, as well as to have a dedicated team member for this task, are essential to ensure equitable responsibility for the study‐related costs and to avoid discontinuation of trials. [ABSTRACT FROM AUTHOR]

Background: Approximately one third of thromboembolic (TE) events are related to obesity, but to which extent elevated body mass index (BMI) during the distinct periods of childhood and puberty contributes is not known. We aimed to evaluate the impact of high BMI during childhood and puberty for the risk of adult venous and arterial thromboembolic events (VTE, ATE, respectively) in men. Methods: We included 37,672 men from the BMI Epidemiology Study (BEST) Gothenburg with data on weight and height in childhood, young adult age, and on pubertal BMI change. Information on outcomes (VTE [n = 1683], ATE [n = 144], or any first TE event [VTE or ATE; n = 1780]) was retrieved from Swedish national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. Results: Both BMI at 8 years of age and the pubertal BMI change were associated with VTE, independently of each other (BMI at 8: HR 1.06 per standard deviation [SD] increase, 95% CI, 1.01;1.11; pubertal BMI change: HR 1.11 per SD increase, 95% CI, 1.06;1.16). Individuals with normal weight during childhood followed by young adult overweight (HR 1.40, 95% CI, 1.15;1.72), and individuals with overweight at both childhood and young adult age (HR 1.48, 95% CI, 1.14;1.92), had a significantly increased risk of VTE in adult life, compared with the normal weight reference group. Individuals with overweight in childhood and in young adult age had increased risk of ATE and TE. Conclusion: Young adult overweight was a strong determinant, and childhood overweight a moderate determinant, of the risk of VTE in adult men. [ABSTRACT FROM AUTHOR]

Background: Birth weight is an indicator of intra-uterine conditions but also a determinant for future health. The importance of preconception health for a healthy birth weight has been emphasized, but evidence is lacking on how modifiable factors in adolescence, such as body mass index (BMI) and smoking, affect future pregnancy outcome. We evaluated associations between BMI and smoking in adolescence and at the start of pregnancy and birth weight of the first-born child. Methods: This longitudinal study included 1256 mothers, born 1962–1992, and their first-born children, born between 1982–2016. Self-reported questionnaire information on weight, height and smoking at age 19 was cross-linked with national register data obtained at the start of pregnancy and with the birth weights of the children. Univariable and multivariable linear regressions were performed to determine the impact of maternal factors at 19 years of age and at the start of the pregnancy respectively, and the importance of BMI status at these points of time for the birth weight of the first child. Results: BMI and smoking at the start of the pregnancy displayed strong associations with birth weight in a multivariable analysis, BMI with a positive association of 14.9 g per BMI unit (95% CI 6.0; 23.8 p = 0.001) and smoking with a negative association of 180.5 g (95% CI -275.7; -85.4) p = 0.0002). Smoking and BMI at 19 years of age did not show this association. Maternal birth weight showed significant associations in models at both time-points. Becoming overweight between age 19 and the start of the pregnancy was associated with a significantly higher birth weight (144.6 (95% CI 70.7;218.5) p = 0.0002) compared to mothers with normal weight at both time points. Conclusions: Our findings indicate that the time period between adolescence and first pregnancy could be a window of opportunity for targeted health promotion to prevent intergenerational transmission of obesity. [ABSTRACT FROM AUTHOR]

The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based BMI Epidemiology Study Gothenburg cohort has weight available from school health care records, and information on melatonin prescription through linkage with high-quality national registers. We included prescriptions of melatonin to individuals below 18 years of age where a weight measurement not earlier than three months before, or later than six months after the dispensing date, was available (n = 1554). Similar maximum doses were prescribed to individuals with overweight orobesity as to individuals with normal weight, and to individuals below and above 9 years of age. Age and weight only explained a marginal part of the variance in maximum dose, but were inversely associated and explained a substantial part of the variance in maximum dose per kg. As a result, individuals overweight or with obesity, or age above 9 years, received lower maximum dose per kg of body weight, compared with individuals with normal weight or below 9 years of age. Thus, the prescribed melatonin dose to individuals under 18 years of age is not primarily informed by body weight or age, resulting in substantial differences in prescribed dose per kg of body weight across BMI and age distribution. [ABSTRACT FROM AUTHOR]

Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regard to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population‐specific factors (e.g., more frequent use of off‐label/unlicensed drugs). In recognition of these challenges, a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life‐cycle of medicinal products which are described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development, safety data collection and analysis. Furthermore, they describe the specific details of post‐marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record‐linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit–risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life‐cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs. [ABSTRACT FROM AUTHOR]

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease‐ and/or target organ‐specific examples. Identifying and testing PD targets and effects in special populations, and application of age‐ and/or population‐specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD‐related as well as drug safety‐related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development. [ABSTRACT FROM AUTHOR]

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost‐effectiveness of a new children's treatment has several non‐trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a common yet largely underdiagnosed disease. This study aimed to test the feasibility of incorporating a non-targeted CD screening in a pediatric outpatient setting and evaluate its short-term impact on children with serological evidence of disease. Over five months, 500 children (aged 2–17 years) attending a general pediatric outpatient clinic in Gothenburg, Sweden, were enrolled and surveyed for current symptoms, quality of life, and background characteristics; 481 children were screened for tissue-transglutaminase antibodies (tTGA); repeated tTGA-positivity was defined as CD autoimmunity (CDA). Children with CDA were investigated for CD and for one year monitored for changes in symptoms, and quality of life. Eleven of 481 (2.3%) screened children had CDA. Children with CDA were younger (median 3.8 years) than those without CDA (8.8 years). No other major between-group differences were reported in background characteristics, symptoms, or quality of life. The screening was well-accepted by the families/participants. During 1-year follow-up, 8 of 11 children with CDA were diagnosed with CD. Children with screening-detected CD reported no significant changes in symptoms and quality of life and the dietary adherence rate was good. Non-targeted screening for CD was feasible in a general pediatric outpatient setting. While hampered by small sample size, our results are in line with previous screening studies indicating that symptoms do not differentiate CDA from non-CDA children. Also, among an overall minimal-symptomatic group of children, diagnosing CD and installation of treatment did not significantly change their well-being during 1-year follow-up. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to present prevalence data for overweight and obesity across school age in a large, recent, population‐based cohort of children in Gothenburg, Sweden. Methods: We included 66,807 children (48.5% girls) aged 5–18.9 years who had their height and weight measured in school health care 2015–2018. The BMI values were categorised according to the age‐dependent cut‐offs for overweight and obesity from the International Obesity Task Force (IOTF). Results: Overall, the prevalence of overweight and obesity for girls and boys was 18.1% and 18.0%, respectively. We observed increasing proportions of overweight (girls 11.5–17.1% and boys 8.4–17.4%) and obesity (girls 3.0–4.2% and boys 2.7–6.1%) with increasing age (p < 0.001 for trend in both sexes). Moreover, girls had higher prevalence of overweight during ages 5.0 to 8.9 years compared with boys (p < 0.001), while boys had higher prevalence of obesity 15.0–18.9 years compared with girls (p < 0.001). Conclusion: In conclusion, we demonstrate increasing prevalence of overweight and obesity across the entire school age range, as well as differences in prevalences between boys and girls, in a population‐based sample of 67,000 children in Gothenburg city, Sweden. Continuous monitoring of schoolchildren, together with effective preventive measures, is crucial to curb the obesity epidemic and its consequences. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that a high body mass index (BMI) is a risk factor for severe COVID-19. The aim of the present study was to assess whether a high BMI affects the risk of death or prolonged length of stay (LOS) in patients with COVID-19 during intensive care in Sweden. Methods and findings: In this observational, register-based study, we included patients with COVID-19 from the Swedish Intensive Care Registry admitted to intensive care units (ICUs) in Sweden. Outcomes assessed were death during intensive care and ICU LOS ≥14 days. We used logistic regression models to evaluate the association (odds ratio [OR] and 95% confidence interval [CI]) between BMI and the outcomes. Valid weight and height information could be retrieved in 1,649 patients (1,227 (74.4%) males) with COVID-19. We found a significant association between BMI and the risk of the composite outcome death or LOS ≥14 days in survivors (OR per standard deviation [SD] increase 1.30, 95%CI 1.16–1.44, adjusted for sex, age and comorbidities), and this association remained after further adjustment for severity of illness (simplified acute physiology score; SAPS3) at ICU admission (OR 1.30 per SD, 95%CI 1.17–1.45). Individuals with a BMI ≥ 35 kg/m2 had a doubled risk of the composite outcome. A high BMI was also associated with death during intensive care and a prolonged LOS in survivors assessed as separate outcomes. The main limitations were the restriction to the first wave of the pandemic, and the lack of information on socioeconomic status as well as smoking. Conclusions: In this large cohort of Swedish ICU patients with COVID-19, a high BMI was associated with increasing risk of death and prolonged length of stay in the ICU. Based on our findings, we suggest that individuals with obesity should be more closely monitored when hospitalized for COVID-19. [ABSTRACT FROM AUTHOR]

• The MMR vaccine has been hypothesised to protect against SARS-CoV-2 / COVID-19. • A measles outbreak in 2018 meant that many health care workers received MMR. • A test negative case-control study was performed in 5905 health care workers. • The OR for testing positive in recently vs not recently MMR-vaccinated was 0.91. • The OR in males was 0.43, suggesting a protective effect in males but not females. It has been hypothesised that the measles-mumps-rubella (MMR) vaccine may afford cross-protection against SARS-CoV-2 which may contribute to the wide variability in disease severity of Covid-19. We employed a test negative case-control study, utilising a recent measles outbreak during which many healthcare workers received the MMR vaccine, to investigate the potential protective effect of MMR against SARS-CoV-2 in 5905 subjects (n = 805 males, n = 5100 females). The odds ratio for testing positive for SARS-CoV-2, in recently MMR-vaccinated compared to not recently MMR-vaccinated individuals was 0.91 (95% CI 0.76, 1.09). An interaction analysis showed a significant interaction for sex. After sex-stratification, the odds ratio for testing positive for males was 0.43 (95% CI 0.24, 0.79, P = 0.006), and 1.01 (95% CI 0.83, 1.22, P = 0.92) for females. Our results indicate that there may be a protective effect of the MMR vaccine against SARS-CoV-2 in males but not females. [ABSTRACT FROM AUTHOR]

Background: The role of pubertal BMI change in adult‐onset concomitant asthma and allergic rhinitis is unknown. Objective: We investigated the association of childhood and young adult BMI, and pubertal BMI changes with adult‐onset asthma, allergic rhinitis, and concomitant asthma and rhinitis in Swedish men. Methods: The BMI Epidemiology Study in Gothenburg, Sweden, comprised of height and weight measures taken from school health records (6.5‐9.5 years) and during military conscription (17.5‐22 years) for all men born 1945‐1961 (n = 37 652). Age‐adjusted childhood BMI centred at 8 years and young adult BMI at 20 years were linked to high quality data on asthma and allergic rhinitis diagnoses from the Swedish National Patient Register. Findings: High BMI (4th quartile vs the two median quartiles) at 8 years was associated with increased risk of concomitant asthma and allergic rhinitis (HR 1.45; 95% CI 1.00‐2.11). Overweight (HR 1.45; 95% CI 1.12‐1.89) and obesity (HR 1.95; 95% CI 1.08‐3.54) at 20 years were associated with increased risk of asthma without concomitant allergic rhinitis as main or auxiliary diagnosis. Pubertal BMI change showed a non‐linear association, so that both low (1st quartile vs the two median quartiles) and high pubertal BMI changes were associated with increased risk of asthma (low: HR 1.36; 95% CI 1.11‐1.68; high: HR 1.32; 95% CI 1.07‐1.63) and asthma without concomitant allergic rhinitis (low: HR 1.33; 95% CI 1.04‐1.69; high: HR 1.36; 95% CI 1.07‐1.74) as a main diagnosis. Conclusions and Clinical Relevance: Both low and high pubertal BMI changes are predictors of adult‐onset asthma in men, particularly asthma without concomitant allergic rhinitis. Primary prevention of adult‐onset asthma requires monitoring of changes in BMI during puberty. [ABSTRACT FROM AUTHOR]

Simple Summary: Men's pubertal timing lacks distinct markers that are easily available retrospectively. Therefore, the association between objectively assessed pubertal timing and the risk of prostate cancer is unknown. Our aim was to evaluate the association between the age at the pubertal growth spurt, an objective assessment of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. We used a population-based cohort including over 30,000 men with age at the pubertal growth spurt available and with follow-up in high quality national registers. During 1.4 million years of follow up, 1759 cases of prostate cancer were diagnosed. We demonstrate that late pubertal timing is a protective factor for prostate cancer, and especially for the clinically important high-risk or metastatic prostate cancer. Identification of early life risk- and protective factors for prostate cancer could provide new opportunities to unravel the underlying biological mechanism of the origins of prostate cancer. Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids. [ABSTRACT FROM AUTHOR]

The bone-sparing effect of estrogen in both males and females is primarily mediated via estrogen receptor-α (ERα), encoded by the Esri gene. ERa in osteoclasts is crucial for the trabecular bone-sparing effect of estrogen in females, but it is dispensable for trabecular bone in male mice and for cortical bone in both genders. We hypothesized that ERα in osteocytes is important for trabecular bone in male mice and for cortical bone in both males and females. Dmp1-Cre mice were crossed with ERαflox/flox mice to generate mice lacking ERα protein expression specifically in osteocytes (Dmp1-ERα-1-). Male Dmp1-ERα-1- mice displayed a substantial reduction in trabecular bone volume (-20%. P <0.01) compared with controls. Dynamic histomorphometry revealed reduced bone formation rate (-45%, P < 0.01) but the number of osteodasts per bone surface was unaffected in the male Dmp1-ERα-1- mice. The male Dmp1-ERα-1- mice had reduced expression of several osteo-blast/osteocyte markers in bone. induding Runx2. 5p7. and Dmpl (P < 0.05). Gonadal intact Dmp1-ERα-1- female mice had no significant reduction in trabecular bone volume but ovanectomized Dmp1-ERα-1- female mice displayed an attenuated trabecular bone response to supraphysiological E2 treatment Dmpl-ERα-1- mice of both genders had unaffected cortical bone. In conclusion. ERa in osteocytes regulates trabecular bone formation and thereby trabecular bone volume in male mice but it is dispensable for the trabecular bone in female mice and the cortical bone in both genders. We propose that the physiological trabecular bone-sparing effect of estrogen is mediated via ERa in osteocytes in males, but via ERa in osteoclasts in females. [ABSTRACT FROM AUTHOR]

Objective: Age at adiposity rebound (AR) is associated with obesity and Type 2 Diabetes in adults. The aim of the present study was to investigate the role of age at AR in adult fat mass, fat distribution and pubertal timing for a Swedish cohort. Patients and Methods: This is a retrospective cohort study. Detailed growth charts were retrieved for the men participating in the population-based GOOD (Gothenburg Osteoporosis and Obesity Determinants) study (n = 573). Body composition was analysed using dual X-ray absorptiometry and computed tomography at 18-20 years of age. Age and BMI at AR were calculated using pediatric growth charts and AR was defined as the lowest BMI between 3 and 9 years of age. Results: Subjects were divided into early (age at AR below 5.4 years of age), middle (age at AR 5.4 to 6.8 years of age) and late (age at AR after 6.8 years of age) age at AR tertiles. Subjects in the early age at AR tertile had higher young adult BMI (+8%), whole body fat mass (+34%) and amount of subcutaneous adipose tissue (+61%) than the subjects in the middle and late tertiles (p,0.01). The early age at AR tertile had an increased risk of obesity (Odds Ratio 4.1 [95% CI 1.2-13.9]) compared with the middle and late tertiles. In addition, the early age at AR tertile had Peak Height Velocity (PHV) 7 months earlier than the late tertile. Conclusions: Early age at AR was associated with young adult obesity as a consequence of a high amount of subcutaneous adipose tissue in men. In addition we made the novel observation that early age at AR was associated with an early puberty in men. [ABSTRACT FROM AUTHOR]

Objective: The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how BMI changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous and visceral fat mass by BMI changes during childhood and adolescence.Research Design and Methods: Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study (n = 612). Body composition was analyzed using dual-energy X-ray absorptiometry and adipose tissue areas using abdominal computed tomography at 18 to 20 years of age.Results: The main finding in the present study was that subjects with increases in BMI Z score of more than 1 SD during adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%; P < 0.001) and visceral adipose tissue areas (+91%; P < 0.001) than subjects with unchanged BMI Z-score. In contrast, subjects with increases in BMI Z score of more than 1 SD during late childhood had a larger amount of adult subcutaneous adipose tissue (+83%; P < 0.001) than subjects with unchanged BMI Z score but an unaffected amount of visceral adipose tissue. BMI changes during adolescence predict both visceral and subcutaneous adipose tissue of the abdomen, whereas BMI changes during late childhood predict only the subcutaneous adipose tissue.Conclusions: The amount of visceral adipose tissue in young adult men was associated with BMI changes specifically during adolescence, whereas the amount of subcutaneous adipose tissue was associated with BMI changes during both late childhood and adolescence. [ABSTRACT FROM AUTHOR]

Most patients with the syndrome &rbline;esistance to &tbline;hyroid &hbline;ormone (RTH) express a mutant thyroid hormone receptor β (TRβ) with transdominant negative transcriptional effects. Since no patient with a mutant TRα has been identified, we introduced a point mutation into the mouse thyroid hormone receptor (TRα1) locus originally found in the TRβ gene, that reduces ligand binding 10-fold. Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. Homozygous mice died before 3 weeks of age. Adult heterozygotes overcome most of these defects except for cardiac function abnormalities, suggesting that other factors compensate for the receptor defect. However, the additional deletion of the TRβ gene in this mouse strain caused a 10-fold increase in serum thyroxine, restored hormonal regulation of target genes for TRs, and rescued the growth retardation. The data demonstrate a novel array of effects mediated by a dominant negative TRα1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment. [ABSTRACT FROM AUTHOR]