Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.

Major cardiovascular events and death in parents of children with type 1 diabetes: a register-based matched cohort study in Sweden.

AIMS/HYPOTHESIS: Parenting a child with type 1 diabetes has been associated with stress-related symptoms. This study aimed to elucidate the potential impact on parental risk of major cardiovascular events (MCE) and death. METHODS: In this register-based study, we included the parents of 18,871 children, born 1987-2020 and diagnosed with type 1 diabetes in Sweden at <18 years. The median parental age at the child's diagnosis was 39.0 and 41.0 years for mothers and fathers, respectively. The cohort also encompassed 714,970 population-based matched parental control participants and 12,497 parental siblings. Cox proportional hazard regression models were employed to investigate the associations between having a child with type 1 diabetes and incident MCE and all-cause death, and, as secondary outcomes, acute coronary syndrome and ischaemic heart disease (IHD). We adjusted for potential confounders including parental type 1 diabetes and country of birth. RESULTS: During follow-up (median 12 years, range 0-35), we detected no associations between parenting a child with type 1 diabetes and MCE in mothers (adjusted HR [aHR] 1.02; 95% CI 0.90, 1.15) or in fathers (aHR 1.01; 95% CI 0.94, 1.08). We noted an increased hazard of IHD in exposed mothers (aHR 1.21; 95% CI 1.05, 1.41) with no corresponding signal in fathers (aHR 0.97; 95% CI 0.89, 1.05). Parental sibling analysis did not confirm the association in exposed mothers (aHR 1.01; 95% CI 0.73, 1.41). We further observed a slightly increased hazard of all-cause death in exposed fathers (aHR 1.09; 95% CI 1.01, 1.18), with a similar but non-significant estimate noted in exposed mothers (aHR 1.07; 95% CI 0.96, 1.20). The estimates from the sibling analyses of all-cause death in fathers and mothers were 1.12 (95% CI 0.90, 1.38) and 0.73 (95% CI 0.55, 0.96), respectively. CONCLUSIONS/INTERPRETATION: Having a child diagnosed with type 1 diabetes in Sweden was not associated with MCE, but possibly with all-cause mortality. Further studies are needed to disentangle potential underlying mechanisms, and to investigate parental health outcomes across the full lifespan.

Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort.

BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates. METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid ß-oxidation, and amino acid degradation were associated with coronary artery calcium score. CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.

Sociodemographic characteristics and COVID-19 testing rates: spatiotemporal patterns and impact of test accessibility in Sweden.

BACKGROUND: Diagnostic testing is essential for disease surveillance and test-trace-isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates. METHODS: We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8-1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood. RESULTS: We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5-69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5-14 years) ranging from 0.56 (95% CI 0.47-0.67) to 0.87 (95% CI 0.80-0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10-18% decrease in inhabitants 15-29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70-105, supporting an intervention effect. CONCLUSIONS: Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.

Sleep duration is associated with protein biomarkers for cardiometabolic health: A large-scale population study.

Sleep problems and short sleep duration have been linked to adverse health effects, such as cardiovascular disease and diabetes, but the mechanisms are not fully understood. Finding biomarkers could explain mechanistic pathways and help in understanding relationships between sleep and cardiometabolic health. The aim was to assess if sleep duration and sleep quality affect the cardiometabolic-related protein profile. In total, 242 proteins related to cardiometabolic health were measured in 2,430 plasma samples (male:female ratio 1:1, aged 45-75 years) from the population-based EpiHealth cohort, using a proximity extension assay. The association of self-reported sleep duration and sleep quality with each of the 242 proteins (primary outcome) was assessed with linear regression modelling, adjusting for confounders, and corrected for multiple testing using the false discovery rate (5%). Potential effect modification of age and sex was also tested using an interaction term. We identified U-shaped associations between sleep duration and the plasma levels of the proteins follistatin (more prominent in younger individuals), matrix metallopeptidase 9 (men only), urokinase receptor, adrenomedullin and kidney injury molecule, all previously known to be related to cardiovascular risk. There was no relationship between sleep quality and any of the proteins, after adjustment for confounders. These results give new leads to investigate the potential mechanistic pathways between sleep and cardiometabolic health.

Global Plasma Metabolomics to Identify Potential Biomarkers of Blood Pressure Progression.

OBJECTIVE: The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approach and Results: Circulating metabolite levels were assessed with liquid- and gas-chromatography coupled to mass spectrometry among persons without BP-lowering medication at baseline. We studied associations of baseline levels of metabolites with changes in BP levels and the clinical BP stage between baseline and a follow-up examination 5 years later. In the discovery cohort, we investigated 504 individuals that contributed with 757 observations of paired BP measurements. The mean baseline systolic and diastolic BPs were 144 (19.7)/76 (9.7) mm Hg, and change in systolic and diastolic BPs were 3.7 (15.8)/-0.5 (8.6) mm Hg over 5 years. The metabolites associated with diastolic BP change were ceramide, triacylglycerol, total glycerolipids, oleic acid, and cholesterylester. No associations with longitudinal changes in systolic BP or BP stage were observed. Metabolites with similar structures to the 5 top findings in the discovery cohort were investigated in the validation cohort. Diacylglycerol (36:2) and monoacylglycerol (18:0), 2 glycerolipids, were associated with diastolic BP change in the validation cohort. CONCLUSIONS: Circulating baseline levels of ceramide, triacylglycerol, total glycerolipids, and oleic acid were positively associated with longitudinal diastolic BP change, whereas cholesterylester levels were inversely associated with longitudinal diastolic BP change. Two glycerolipids were validated in an independent cohort. These metabolites may point towards pathophysiological pathways of hypertension.

Multiplicity of Asymptomatic Plasmodium falciparum Infections and Risk of Clinical Malaria: A Systematic Review and Pooled Analysis of Individual Participant Data.

BACKGROUND: The malaria parasite Plasmodium falciparum holds an extensive genetic polymorphism. In this pooled analysis, we investigate how the multiplicity in asymptomatic P. falciparum infections-that is, the number of coinfecting clones-affects the subsequent risk of clinical malaria in populations living under different levels of transmission. METHODS: A systematic search of the literature was performed to identify studies in which P. falciparum infections were genotyped in asymptomatic individuals who were followed up prospectively regarding the incidence of clinical malaria. Individual participant data were pooled from 15 studies (n = 3736 individuals). RESULTS: Multiclonal asymptomatic infections were associated with a somewhat increased subsequent risk of clinical malaria in the youngest children, followed by an initial declining risk with age irrespective of transmission intensity. At approximately 5 years of age, the risk continued the gradual decline with age in high-transmission settings. However, in older children in moderate-, low-, and seasonal-transmission settings, multiclonal infections were either not significantly associated with the risk of subsequent febrile malaria or were associated with an increased risk. CONCLUSIONS: The number of clones in asymptomatic P. falciparum infections is associated with different risks of subsequent clinical malaria depending on age and transmission intensity.

Health Care Costs of Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease Are Nearly Twice Those of Matched Controls.

BACKGROUND & AIMS: Data on healthcare resource use and costs associated with nonalcoholic fatty liver disease (NAFLD) in clinical practice are lacking. We compared real-life healthcare costs of patients with NAFLD to matched controls. METHODS: We performed a retrospective study of 646 patients with biopsy-proven NAFLD in Sweden from 1971 through 2009. Each patient was matched for age, sex, and county of residence with 10 persons from the general population (controls). We retrieved all healthcare contacts through Dec 31, 2014 from national registers. Unit costs were assigned to arrive at a total healthcare cost (in USD [$]) per study subject. RESULTS: During a mean follow-up of 19.9 years, we recorded a mean of 0.27 hospitalizations per year for patients with NAFLD vs 0.16 for controls (P < .001). This corresponded to an incremental cost of $635 per year for patients with NAFLD. Patients with NAFLD had a higher mean use of outpatient care visits: 1.46 contacts per year compared with 0.86 per year in controls, corresponding to $255 in additional costs (P < .001). Total costs incurred by patients with stage 3-4 fibrosis were higher than by patients with fibrosis stage 0-2 (mean annual costs, $4397 vs $629). Cumulative costs were higher for all stages of fibrosis compared to controls. CONCLUSIONS: Healthcare costs are nearly twice as high in patients with NAFLD than in matched controls. This is mostly attributable to higher costs for hospitalizations, but also to more outpatient visits. Patients with advanced fibrosis had the highest costs.

m-Health for Burn Injury Consultations in a Low-Resource Setting: An Acceptability Study Among Health Care Providers.

Introduction:The rapid adoption of smartphones, especially in low- and middle-income countries, has opened up novel ways to deliver health care, including diagnosis and management of burns. This study was conducted to measure acceptability and to identify factors that influence health care provider's attitudes toward m-health technology for emergency care of burn patients.Methods:An extended version of the technology acceptance model (TAM) was used to assess the acceptability toward using m-health for burns. A questionnaire was distributed to health professionals at four hospitals in Dar Es Salaam, Tanzania. The questionnaire was based on several validated instruments and has previously been adopted for the sub-Saharan context. It measured constructs, including acceptability, usefulness, ease of use, social influences, and voluntariness. Univariate analysis was used to test our proposed hypotheses, and structural equation modeling was used to test the extended version of TAM.Results:In our proposed test-model based on TAM, we found a significant relationship between compatibility-usefulness and usefulness-attitudes. The univariate analysis further revealed some differences between subgroups. Almost all health professionals in our sample already use smartphones for work purposes and were positive about using smartphones for burn consultations. Despite participants perceiving the application to be easy to use, they suggested that training and ongoing support should be available. Barriers mentioned include access to wireless internet and access to hospital-provided smartphones.

Serum Markers Associated with Severity and Outcome of Hantavirus Pulmonary Syndrome.

BACKGROUND: Hantavirus pulmonary syndrome (HPS) is caused by Andes virus (ANDV) and related hantaviruses in the Americas. Despite a fatality rate of 40%, the pathogenesis of HPS is poorly understood and factors associated with severity, fatality, and survival remain elusive. METHODS: Ninety-three ANDV-infected HPS patients, of whom 34 had a fatal outcome, were retrospectively studied. Serum levels of cytokines and other inflammation-associated markers were analyzed using multiplex immunoassay and enzyme-linked immunosorbent assay. Associations with disease severity, fatal outcome, and survival were identified using logistic regression. RESULTS: HPS patients exhibited increased serum levels of markers associated with inflammation, intestinal damage, and microbial translocation compared to controls. Patients with fatal outcome displayed higher levels of interleukin (IL) 6, IL-10, interferon-γ, soluble tumor necrosis factor-related apoptosis-inducing ligand, and intestinal fatty acid-binding protein (I-FABP) than survivors. Levels of complement factor 5/5a were higher in survivors compared with fatal cases. IL-6 and I-FABP, the latter a marker for intestinal damage, were by multivariate analyses identified as independent markers associated with disease severity (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.01-5.01) and fatal outcome (OR, 1.64; 95% CI, 1.01-2.64), respectively. CONCLUSIONS: HPS patients displayed a multifaceted, systemic inflammatory response, with IL-6 and I-FABP as independent markers of disease severity and fatality, respectively.

Rates and characteristics of postcolonoscopy colorectal cancer in the Swedish IBD population: what are the differences from a non-IBD population?

OBJECTIVE: The rate of postcolonoscopy colorectal cancer (PCCRC) is considered a key quality indicator of colonoscopy; little is known about PCCRC in IBD. DESIGN: A population-based cohort study of colonoscopies in Sweden from 2001 to 2010 was conducted. Individuals with a colorectal cancer (CRC) detected within 36 months after a colonoscopy were identified and stratified on UC, Crohn's disease (CD) or non-IBD. The CRCs were classified as detected CRCs (dCRC) (0-6 months) or as PCCRCs (6-36 months). PCCRC rates were calculated by the number of false negative/(the number of true positive+the number of false negative) colonoscopies. Poisson regression analysis was employed to examine the association between PCCRC and IBD (CD and UC) diagnosis, age, gender, location, time period and comorbidities. RESULTS: We identified 348 232 colonoscopies in 270 918 individuals. Of these, 27 123 were performed on 14 597 individuals with CD, and 51 572 were performed on 26 513 individuals with UC. There were 13 317 CRCs in the non-IBD group, 133 in the CD group and 281 in the UC group. The PCCRC rate in the CD group was 28.3% and 41.0% in the UC group. The RR for a PCCRC was 3.82 (95% CI 2.94 to 4.96) in CD and 5.89 (95% CI 5.10 to 6.80) in UC, compared with non-IBD. The highest risk was observed among rectal cancer location in CD and in younger individuals with UC. CONCLUSION: The high rates of PCCRC in young patients with UC and for rectal cancer location in CD might affect future performance of IBD surveillance.

Temporal Dynamics and Risk Factors for Bloodstream Infection With Extended-spectrum ß-Lactamase-producing Bacteria in Previously-colonized Individuals: National Population-based Cohort Study.

Background: Little is known of the long-term risks of bloodstream infection (BSI) with extended spectrum ß-lactamase-producing Enterobacteriaceae (EPE) in previously-colonized individuals. We investigated EPE-BSI risks and associated risk factors during 6 years following EPE colonization. Methods: We performed a population-based cohort study in Sweden using national health registers. Subjects were followed from their first EPE finding in feces (n = 5513) or urine (n = 17189). The effects of co-morbidity, sociodemography, and outpatient antibiotic dispensation on EPE-BSI risks were assessed. The EPE-BSI risks were compared to those of 45161 matched population-based reference subjects. Results: The cumulative 6-year EPE-BSI incidences were 3.8%, 1.6%, and 0.02% in the urine, feces, and reference cohorts, respectively. The incidences decreased exponentially during the first 6-12 months. Among EPE-exposed subjects, urological disorders were associated with the highest adjusted cause-specific hazard ratio (aCSHR) for subsequent EPE-BSIs (3.40, 95% confidence interval 2.47-4.69). The aCSHRs were between 1.62-2.20 for male sex, immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and Klebsiella pneumoniae, compared to the Escherichia coli baseline sample. Antibiotics with selective activity against gram-negative bacilli-but mostly not EPE (trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins, and penicillins with extended spectrums)-and pivmecillinam were associated with doubled EPE BSI risk during the 3 months after antibiotic dispensation in EPE-colonized subjects. Conclusions: EPE in urine or feces is a substantial risk factor for subsequent EPE-BSIs, but the risk declines rapidly during the first year after detection. In EPE-colonized individuals, specific risk factors can be used to identify subgroups for targeted interventions, such as eradication therapy.

Minimum Inhibitory Concentrations of Fluoroquinolones and Pyrazinamide Susceptibility Correlate to Clinical Improvement in Multidrug-resistant Tuberculosis Patients: A Nationwide Swedish Cohort Study Over 2 Decades.

BACKGROUND: Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant (MDR)-tuberculosis patients is unclear. Therefore, we correlated MICs of first- and second-line tuberculosis drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-tuberculosis patients. METHODS: Clinical and demographic data of MDR-tuberculosis patients in Sweden, including DST results, were retrieved from medical records from 1992 to 2014. MIC determinations were performed retrospectively for the stored individual Mycobacterium tuberculosis (Mtb) isolates using broth microdilution in Middlebrook 7H9. We fitted Cox proportional hazard models correlating MICs, DST results, and clinical variables to tSCC and treatment outcome. RESULTS: Successful treatment outcome was observed in 83.5% (132/158) of MDR-tuberculosis patients. Increasing MICs of fluoroquinolones, diabetes, and age >40 years were significantly associated with unsuccessful treatment outcome. Patients treated with pyrazinamide (PZA) had a significantly shorter tSCC compared to patients who were not (median difference, 27 days). CONCLUSIONS: Increasing MICs of fluoroquinolones were correlated with unsuccessful treatment outcome in MDR-tuberculosis patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatment was associated with shorter tSCC, highlighting the importance of PZA DST.

Cardiovascular risk factors in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with non-alcoholic fatty liver disease (NAFLD) are at an increased risk for cardiovascular disease (CVD). It is unclear whether histological variables may help predict CVD risk. We evaluated histology and traditional CV risk factors as predictors of CVD outcomes in a large NAFLD cohort. METHODS: We included 603 biopsy-proven NAFLD patients free of baseline CVD and matched these (1:10, by age, sex and municipality) to 6269 population controls. All individuals were cross-linked to national registries to ascertain incident CVD events, defined as acute ischaemic heart disease or stroke. The presence of CV risk factors and liver histology were available in NAFLD patients only. Cox regression models were used to estimate hazard ratios (HR) for incident CVD. RESULTS: During a mean follow-up of 18.6 years, 168 (28%) of NAFLD patients and 1325 (21%) of controls experienced a CVD event (HR 1.54, 95%CI 1.30-1.83). Within the NAFLD cohort, age, male sex, type 2 diabetes, smoking and triglycerides were associated with risk of CVD. Taking these CV risk factors into account, no histological parameter, including presence of NASH and fibrosis stage, were associated with incident CVD. CONCLUSIONS: Patients with NAFLD are at an increased risk for CVD compared to matched controls, but histological parameters do not seem to independently predict this risk.

Malaria in Eritrean migrants newly arrived in seven European countries, 2011 to 2016.

Global migration has resulted in a large number of asylum applications in Europe. In 2014, clusters of Plasmodium vivax cases were reported among newly arrived Eritreans. This study aimed to assess malaria among Eritrean migrants in Europe from 2011 to 2016. We reviewed European migration numbers and malaria surveillance data for seven countries (Denmark, Germany, Netherlands, Norway, Sweden, Switzerland and the United Kingdom) which received 44,050 (94.3%) of 46,730 Eritreans seeking asylum in Europe in 2014. The overall number of malaria cases, predominantly P. vivax, increased significantly in 2014 compared to previous years, with the largest increases in Germany (44 P. vivax cases in 2013 vs 294 in 2014, p < 0.001) and Sweden (18 in 2013 vs 205 in 2014, p < 0.001). Overall, malaria incidence in Eritreans increased from 1-5 to 25 cases per 1,000, and was highest in male teenagers (50 cases/1,000). In conclusion, an exceptional increase of malaria cases occurred in Europe in 2014 and 2015, due to rising numbers of Eritreans with high incidence of P. vivax arriving in Europe. Our results demonstrate potential for rapid changes in imported malaria patterns, highlighting the need for improved awareness, surveillance efforts and timely healthcare in migrants.

Picky eating in Swedish preschoolers of different weight status: application of two new screening cut-offs.

BACKGROUND: Characteristics of picky eaters of different weight status have not been sufficiently investigated. We used two newly developed screening cut-offs for picky eating in the Food fussiness (FF) subscale of the Child Eating Behavior Questionnaire (CEBQ) to investigate the prevalence and characteristics of picky eaters in preschool-aged children with thinness, normal weight, overweight or obesity. METHODS: Data for 1272 preschoolers (mean age 4.9 years) were analyzed. The parent-reported FF subscale ranges from 1 to 5, and two screening cut-offs were applied to classify children as picky eaters (3.0 and 3.33). Structural Equation Modeling was used to study associations with other factors in the CEBQ, the Child Feeding Questionnaire (CFQ) and the Lifestyle Behavior Checklist (LBC). Scores were compared separately for each weight status group. RESULTS: Nearly half of the children were classified as moderate or severe picky eaters (cut-off 3.0) and 30% as severe (cut-off 3.33). For both cut-offs, prevalence was significantly lower in the obesity group. Still, one-third of children with obesity met the cut-off of 3.0 and 17% met the cut-off of 3.33. While picky eaters displayed similar patterns across weight status groups, some differences emerged. Food responsiveness was lower for picky eaters, but the difference was significant only among children with obesity. Slowness in eating was not as pronounced among picky eaters in the obesity group. In the overweight and obesity groups, parents of picky eaters did not report as high pressure to eat, as compared to the thinness or normal weight groups; in the obesity group, parents of picky eaters also perceived their children's weight as lower. In all weight status groups, parents of picky eaters were more likely to report their children had too much screen time, complained about physical activity, and expressed negative affect toward food. CONCLUSIONS: Picky eating was less common but still prevalent among children with obesity. Future studies should investigate the potential influence of picky eating on childhood overweight and obesity. Moreover, as children with picky eating display higher emotional sensitivity, further research is needed to understand how to create positive eating environments particularly for children with picky eating and obesity.

Vitamin D supplementation to persistent carriers of MRSA-a randomized and placebo-controlled clinical trial.

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to all beta-lactam antibiotics and can cause severe infections that are difficult to treat. Eradication strategies with conventional antibiotics are not always effective and alternative approaches are warranted. Here, we tested the hypothesis that daily supplementation with vitamin D for 12 months would reduce MRSA carriage rates among a group of persistent carriers. This was a double-blind, placebo-controlled randomized trial with n = 65 persistent MRSA carriers with 25-hydroxy vitamin D3 (25OHD) < 75 nmol/L, who were followed up with bacterial cultures at baseline and every 3 months for 1 year. The primary endpoint was the decline in MRSA positivity during the study period. The study was conducted in two MRSA outpatient clinics at the Karolinska University Hospital, Stockholm, Sweden. In total, n = 65 persistent MRSA carriers were randomized and n = 3 were lost to follow-up. Only patients deficient in vitamin D (< 75 nmol/L) were included. Vitamin D (4000 IU) or placebo/day was administered for 12 months. The decline in MRSA positivity was equal in the vitamin D and placebo group during the study period (OR, 1.00; 95% CI, 0.97-1.03; p = 0.928) and approximately 40% in both groups were MRSA-negative after 12 months. The vitamin D group produced 103 positive cultures out of 318 cultures (32.4%) from nose, throat, and perineum over the study period, whereas the placebo group produced 135/393 positive cultures (34.0%) (Fisher's exact test, p = 0.94). Vitamin D supplementation did not influence MRSA carriage. Thus, available data does not support vitamin D supplementation to persistent MRSA carriers.Trial registration: www.clinicaltrials.gov ; NCT02178488.

The FGF23-Klotho axis and cardiac tissue Doppler imaging in pediatric chronic kidney disease-a prospective cohort study.

BACKGROUND: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. METHODS: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m2) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m2) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI). RESULTS: The prevalence of high FGF23 levels (≥95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during follow-up in CKD and CKD-T patients (ß = -0.2, p < 0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (ß = 1.8, p = 0.06). In addition, high log FGF23 (ß = -0.43, p = 0.01) and low log Klotho (ß = 0.44, p = 0.006) over time were associated with a worse left ventricular diastolic function (cc-TDI e'/a') in CKD-T patients. CONCLUSIONS: In pediatric CKD and CKD-T patients, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation.

Predictors for Employment Status in People With Multiple Sclerosis: A 10-Year Longitudinal Observational Study.

OBJECTIVE: To identify predictors for employment status after 10 years in a cohort of people with multiple sclerosis (MS), with the aim to increase knowledge concerning factors present at an early stage that are important for working life and work-life balance. DESIGN: A 10-year longitudinal observational cohort study. SETTING: University hospital. PARTICIPANTS: A consecutive sample of people with MS (N=154) of working age were included at baseline, of which a total of 116 people participated in the 10-year follow-up; 27 people declined participation and 11 were deceased. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Baseline data on personal factors and functioning were used as independent variables. Employment status 10 years after baseline, categorized as full-time work, part-time work, and no work, was used as the dependent variable. A generalized ordinal logistic regression was used to analyze the predictive value of the independent variables. RESULTS: Predictors for full- or part-time work after 10 years were young age (P=.002), low perceived physical impact of MS (P=.02), fatigue (P=.03), full-time work (P=.001), and high frequency of social/lifestyle activities (P=.001) at baseline. Low perceived physical impact of MS (P=.02) at baseline also predicted full-time work after 10 years. CONCLUSIONS: This study underlines the complexity of working life for people with MS, and indicates that it may be valuable to give more attention to the balance between working and private life, both in clinical practice and future research, to achieve a sustainable working life over time.

The Smart City Active Mobile Phone Intervention (SCAMPI) study to promote physical activity through active transportation in healthy adults: a study protocol for a randomised controlled trial.

BACKGROUND: The global pandemic of physical inactivity represents a considerable public health challenge. Active transportation (i.e., walking or cycling for transport) can contribute to greater total physical activity levels. Mobile phone-based programs can promote behaviour change, but no study has evaluated whether such a program can promote active transportation in adults. This study protocol presents the design and methodology of The Smart City Active Mobile Phone Intervention (SCAMPI), a randomised controlled trial to promote active transportation via a smartphone application (app) with the aim to increase physical activity. METHODS/DESIGN: A two-arm parallel randomised controlled trial will be conducted in Stockholm County, Sweden. Two hundred fifty adults aged 20-65 years will be randomised to either monitoring of active transport via the TRavelVU app (control), or to a 3-month evidence-based behaviour change program to promote active transport and monitoring of active travel via the TRavelVU Plus app (intervention). The primary outcome is moderate-to-vigorous intensity physical activity (MVPA in minutes/day) (ActiGraph wGT3x-BT) measured post intervention. Secondary outcomes include: time spent in active transportation measured via the TRavelVU app, perceptions about active transportation (the Transport and Physical Activity Questionnaire (TPAQ)) and health related quality of life (RAND-36). Assessments are conducted at baseline, after the completed intervention (after 3 months) and 6 months post randomisation. DISCUSSION: SCAMPI will determine the effectiveness of a smartphone app to promote active transportation and physical activity in an adult population. If effective, the app has potential to be a low-cost intervention that can be delivered at scale. TRIAL REGISTRATION: ClinicalTrials.gov NCT03086837 ; 22 March, 2017.