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Background: Preeclampsia is a leading cause of maternal morbidity, and dyslipidemia has been associated with preeclampsia in observational studies. We use Mendelian randomization analyses to estimate the association between lipid levels, their pharmacological targets, and the risk of preeclampsia in 4 ancestry groups. Methods: We extracted uncorrelated ( R 2 P -8 ) with LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), and triglycerides from genome-wide association studies of European, admixed African, Latino, and East Asian ancestry participants. Genetic associations with risk of preeclampsia were extracted from studies of the same ancestry groups. Inverse-variance weighted analyses were performed separately for each ancestry group before they were meta-analyzed. Sensitivity analyses were conducted to evaluate bias due to genetic pleiotropy, demography, and indirect genetic effects. Results: The meta-analysis across 4 ancestry groups included 1.5 million subjects with lipid measurements, 7425 subjects with preeclampsia, and 239 290 without preeclampsia. Increasing HDL-C was associated with reduced risk of preeclampsia (odds ratio, 0.84 [95% CI, 0.74–0.94]; P =0.004; per SD increase in HDL-C), which was consistent across sensitivity analyses. We also observed cholesteryl ester transfer protein inhibition—a drug target that increases HDL-C—may have a protective effect. We observed no consistent effect of LDL-C or triglycerides on the risk of preeclampsia. Conclusions: We observed a protective effect of elevated HDL-C on risk of preeclampsia. Our findings align with the lack of effect in trials of LDL-C modifying drugs but suggest that HDL-C may be a new target for screening and intervention.

BackgroundHigh ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, the incidence is increasing, and in the United States it disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood ALL.MethodsWe used data from California birth records (1982-2015) and California Cancer Registry (1988-2015) to identify ALL cases diagnosed FindingsOur study included 6,258 ALL cases and 307,579 controls. The peak association between ambient temperature and risk of ALL was observed in gestational week 8, where a 5 °C increase was associated with an odds ratio of 1.09 (95% confidence interval 1.04-1.14) and 1.05 (95% confidence interval 1.00-1.11) among Latino and non-Latino White children, respectively. The sensitivity analyses supported this.InterpretationOur findings suggest an association between high ambient temperature in early pregnancy and risk of childhood ALL. Further replication and investigation of mechanistic pathways may inform mitigation strategies.

Previous research suggests decreased immune function and increased risk of infections in individuals with insomnia. We examined the effect of insomnia symptoms on risk of bloodstream infections (BSIs) and BSI-related mortality in a population-based prospective study. A total of 53,536 participants in the second Norwegian Nord-Trøndelag Health Study (HUNT2) (1995-97) were linked to prospective data on clinically relevant BSIs until 2011. In Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for a first-time BSI and for BSI-related mortality (BSI registered ≤30 days prior to death) associated with insomnia symptoms. Compared with participants who reported "no symptoms", participants reporting having "difficulty initiating sleep" (DIS) often/almost every night had a HR for a first-time BSI of 1.14 (95% CI 0.96-1.34). Participants reporting "difficulties maintaining sleep" (DMS) often/almost every night had a HR of 1.19 (95% CI 1.01-1.40), whereas those having a feeling of "non-restorative sleep" once a week or more had a HR of 1.23 (95% CI 1.04-1.46). Participants frequently experiencing all three of the above symptoms had a HR of 1.39 (1.04-1.87), whilst those who had both DIS and DMS had a HR of 1.15 (0.93-1.41) and being troubled by insomnia symptoms to a degree that affected work performance was associated with a HR of 1.41 (95% CI 1.08-1.84). The HRs for BSI-related mortality suggest an increased risk with increasing insomnia symptoms, but the CIs are wide and inconclusive. We found that frequent insomnia symptoms and insomnia symptoms that affected work performance were associated with a weak positive increased risk of BSI.

ImportanceInsomnia has been associated with reduced immune function and increased risk of infections and sepsis in observational studies. These studies are prone to bias, such as residual confounding. To further understand the causal relation between insomnia and sepsis risk we used a two-sample Mendelian randomization (MR) approach.ObjectiveIs genetically predicted insomnia associated with risk of sepsis?DesignTwo-sample MR was performed to estimate the causal effect of genetically predicted insomnia on sepsis risk. Data was obtained from a genome-wide association study (GWAS) identifying 556 independent genetic variants (R2P< 5e-8). We conducted sensitivity analyses to address bias due to pleiotropy and sample overlap, along with mediation analyses.SettingObservational study using genetic variants as instrumental variables in large populations.ParticipantsFor insomnia, 2.4 million subjects of European ancestry from the UK Biobank and 23andMe. For sepsis, 462,918 subjects of European ancestry from the UK Biobank.ExposureGenetically predicted insomnia.Main Outcome and MeasureSepsis.ResultsA doubling in the population prevalence of genetically predicted insomnia was associated with an odds ratio of 1.42 (95% CI 1.23–1.63,P= 9.1e-7) for sepsis. Sensitivity analyses supported this observation. Three quarters of the effect was mediated through body mass index.Conclusions and RelevanceThe concordance between our findings and previous observational studies support of a causal role of genetically predicted insomnia in the risk of sepsis.

Background Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. Methods We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients’ medical records. Regional incidence rates and testing trends were also assessed. Results From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. Conclusions P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.

ObjectiveTo investigate the association between smoking and infertility.DesignProspective study.SettingNationwide cohort.Patients28,606 women and 27,096 men with questionnaire and genotype information from the Norwegian Mother, Father, and Child Cohort Study.InterventionSelf-reported information on smoking (having ever smoked [both sexes], age at initiation [women only], cessation [women only], and cigarettes/week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting these traits were estimated for Mendelian randomization.Main outcome measureInfertility (time-to-pregnancy ≥12 months).ResultsHaving ever smoked was unrelated to infertility in women or men. Higher smoking intensity in women was associated with greater infertility odds (+1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR]crude, 1.19; 95% confidence interval [CI] 1.11–1.28; ORadjusted 1.12; 95% CI, 1.03–1.21), also after adjusting for the partner’s tobacco use. Later smoking initiation (+1 SD [3.2 years]: ORcrude, 0.94; 95% CI, 0.88–0.99; ORadjusted 0.89; 95% CI, 0.84–0.95) and smoking cessation (vs. not quitting: ORcrude, 0.83; 95% CI, 0.75–0.91; ORadjusted, 0.83; 95% CI, 0.75–0.93) were linked to decreased infertility in women. Nevertheless, Mendelian randomization results were not directionally consistent for smoking intensity and cessation and were estimated imprecisely in the 2-sample approach. In men, greater smoking intensity was not robustly associated with infertility in multivariable regression and Mendelian randomization.ConclusionsWe did not find robust evidence of an effect of smoking on infertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding.

Composite endpoints reveal the tendency for statistical convention to arise locally within subfields. Composites are familiar in cardiovascular trials, yet almost unknown in sepsis. However, the VITAMINS trial in patients with septic shock adopted a composite of mortality and vasopressor-free days, and an ordinal scale describing patient status rapidly became standard in COVID studies. Aware that recent use could incite interest in such endpoints, we are motivated to flag their potential value and pitfalls for sepsis research and COVID studies.

Background Bloodstream infection and sepsis are major causes of health loss worldwide, and it is important to identify patients at risk of developing and dying from these conditions. The single-nucleotide polymorphism most strongly associated with sepsis mortality is FER rs4957796. However, it is not known how this variant is associated with bloodstream infection incidence and mortality. Methods We used prospective data from 1995–2017 from the population-based HUNT Study. Genotypes were ascertained from blood samples, and additional genotypes were imputed. Information on bloodstream infection and diagnosis codes at hospitalization were collected through record linkage with all hospitals in the area. Results A total of 69 294 patients were included. Patients with the rs4957796 CC genotype had an increased risk of developing a bloodstream infection compared with the TT genotype (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.00–1.43). However, there was a protective additive effect of the C allele in terms of mortality in the total study population (HR, 0.77; 95% CI, .64–.92 per copy of the C allele) and among bloodstream infection patients (odds ratio, 0.70; 95% CI, .58–.85 per copy of the C allele). The results did not appear to be affected by selection bias. Conclusions The rs4957796 CC genotype was associated with an increased risk of contracting a bloodstream infection but with a reduced risk of dying from one. The latter finding is in line with studies of sepsis case fatality, while the former expands our understanding of the immunoregulatory role of this polymorphism., The C allele of FER rs4957796 has been associated with reduced sepsis case fatality. In this prospective study of 69 294 patients, the C allele increases the risk of developing bloodstream infection but reduces the risk of dying from one.

Previous studies indicate sex differences in incidence and severity of bloodstream infections (BSI). We examined the effect of sex on risk of BSI, BSI mortality, and BSI caused by the most common infecting bacteria. Using causal mediation analyses, we assessed if this effect is mediated by health behaviours (smoking, alcohol consumption), education, cardiovascular risk factors (systolic blood pressure, non-HDL cholesterol, body mass index) and selected comorbidities (cardiovascular disease, chronic kidney disease, diabetes, cancer history and chronic lung disease). This prospective study included 64,040 participants (46.8% men) in the population-based HUNT2 Survey (1995−97) linked with hospital records in incident BSI. During median follow-up of 14.8 years, 1840 (2.9%) participants (51.3% men) experienced a BSI and 396 (0.6%) died (56.6% men). Men had 41% higher risk of first-time BSI (95% confidence interval (CI), 28−54%) than women. Together, health behaviours, education, cardiovascular risk factors and the selected comorbidities mediated 34% of the excess risk of BSI observed in men. The HR of BSI mortality was 1.87 (95%CI, 1.53−2.28), for BSI due to S. aureus 2.09 (1.28−2.54), S. pneumoniae 1.36 (1.05−1.76), and E. coli 0.97 (0.84−1.13) in men vs women. This population-based study shows that men have higher risk of BSI and BSI mortality than women. One-third of this effect was mediated by potential modifiable risk factors for incident BSI. Explaining sex differences in risk of bloodstream infections using mediation analysis in the population-based HUNT study in Norway

ObjectiveTo investigate the association between smoking-related traits and subfertility.DesignProspective study.SettingNationwide cohort in Norway.Patients28,606 women (average age 30) and 27,096 men (average age 33) with questionnaire and genotype information from the Norwegian Mother, Father and Child Cohort Study.InterventionSelf-reported information on smoking (having ever smoked [both sexes], age at smoking initiation [women only], smoking cessation [women only], and cigarettes smoked per week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting the mentioned traits were estimated for Mendelian randomization (MR) analyses.Main outcome measureSubfertility, defined as time-to-pregnancy ≥12 months.ResultsA total of 10% of couples were subfertile. In multivariable regression accounting for age, years of education, body mass index, and number of previous pregnancies, having ever smoked was not linked to subfertility in women or men. A higher intensity of tobacco use in women who were current smokers was related to greater odds of subfertility (+ 1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR] 1.12, 95% confidence interval [CI] 1.03 to 1.21), also after adjusting for the partner’s tobacco use. Later smoking initiation (+ 1 SD [3.2 years]: OR 0.89, 95% CI 0.84 to 0.95) and smoking cessation (relative to not quitting: OR 0.83, 95% CI 0.75 to 0.93) were linked to decreased subfertility in women who had ever smoked. Nevertheless, MR results were not directionally consistent for smoking intensity and cessation and were imprecisely estimated in two-sample MR, with wide confidence intervals that overlapped with the multivariable regression results. In men, greater smoking intensity was marginally linked to greater odds of subfertility in multivariable analyses, but this association was attenuated when adjusting for the partner’s smoking intensity (+ 1 SD [54 cigarettes/week]: OR 1.05, 95% CI 0.96 to 1.15). MR estimates were directionally consistent but again imprecisely estimated.ConclusionsWe did not find robust evidence of an effect of smoking on subfertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding. The relevant limitations across all methods highlights the need for larger studies with information on subfertility.

ObjectiveTo examine the effect of sex on risk of bloodstream infections (BSI) and BSI mortality and to assess to what extent known risk factors for BSI mediate this association in the general population.ParticipantsThe prospective, population-based HUNT2 Survey (1995-97) in Norway invited 93,898 inhabitants ≥20 years in the Nord-Trøndelag region, whereof 65,237 (69.5%) participated. 46.8% of the participants were men.ExposuresSex and potential mediators between sex and BSI; health behaviours (smoking, alcohol consumption), education attainment, cardiovascular risk factors (systolic blood pressure, non-HDL cholesterol, body mass index) and previous or current comorbidities.Main outcome measuresSex differences in risk of first-time BSI, BSI mortality (death within first 30 days after a BSI), BSI caused by the most frequent bacteria, and the impact of known BSI risk factors as mediators.ResultsWe documented a first-time BSI for 1,840 (2.9%) participants (51.3% men) during a median follow-up of 14.8 years. Of these, 396 (0.6%) died (56.6% men). Men had 41% higher risk of any first-time BSI (95% confidence interval (CI), 28 to 54%) than women. An estimated 34% of the excess risk of BSI in men was mediated by known BSI risk factors. The hazard ratio (HR) with 95% CI for BSI due to S. aureus was 2.09 (1.28 to 2.54), S. pneumoniae 1.36 (1.05 to 1.76), and E. coli 0.97 (0.84 to 1.13) in men vs women. BSI related mortality was higher in men compared to women with HR 1.87 (1.53 to 2.28).ConclusionsThis large population-based study show that men have higher risk of BSI than women. One-third of this effect was mediated by known risk factors for BSI. This raises important questions regarding sex specific approaches to reduce the burden of BSI.

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Purpose Severe bacterial infections are important causes of hospitalization and loss of health worldwide. In this study we aim to characterize the total burden, recurrence and severity of bacterial infections in the general population during a 22-year period. Methods We investigated hospitalizations due to bacterial infection from eight different foci in the prospective population-based Trøndelag Health Study (the HUNT Study), where all inhabitants aged ≥ 20 in a Norwegian county were invited to participate. Enrollment was between 1995 and 1997, and between 2006 and 2008, and follow-up ended in February 2017. All hospitalizations, positive blood cultures, emigrations and deaths in the follow-up period were captured through registry linkage. Results A total of 79,393 (69.5% and 54.1% of the invited population) people were included, of which 42,237 (53%) were women and mean age was 48.5 years. There were 37,298 hospitalizations due to infection, affecting 15,496 (22% of all included) individuals. The median time of follow-up was 20 years (25th percentile 9.5–75th percentile 20.8). Pneumonia and urinary tract infections were the two dominating foci with incidence rates of 639 and 550 per 100,000 per year, respectively, and with increasing incidence with age. The proportion of recurring admissions ranged from 10.0% (central nervous system) to 30.0% (pneumonia), whilst the proportion with a positive blood culture ranged from 4.7% (skin- and soft tissue infection) to 40.9% (central nervous system). The 30-day mortality varied between 3.2% (skin- and soft tissue infection) and 20.8% (endocarditis). Conclusions In this population-based cohort, we observed a great variation in the incidence, positive blood culture rate, recurrence and mortality between common infectious diseases. These results may help guide policy to reduce the infectious disease burden in the population.

Objective: Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide. Few studies have previously investigated the genetic susceptibility and potential risk factors for LRTI. Methods: We used data from UK Biobank, HUNT, and FinnGen, to conduct a genome-wide association study (GWAS). Cases were subjects hospitalized with LRTI, and controls were subjects with no such hospitalization. We conducted stratification and interaction analyses to evaluate if the genetic effect of LRTI differed by sex or smoking. Mendelian randomization [MR] analyses were conducted to identify the unconfounded relationship between cardiometabolic risk factors and LRTI. Results: A total of 25,320 cases and 575,294 controls were included. The 15q25.1 locus reached genome-wide significance in the meta-analysis (rs10519203: OR = 0.94, P = 3.87e-11). The protective effect of effect allele of rs10519203 was present among smokers (OR = 0.90 [95% CI = 0.87 - 0.92, P = 1.38e-15]) but not among never-smokers (OR = 1.01 [95% CI = 0.97 - 1.06, P = 5.20e-01]). In MR analyses, we found that increasing body mass index (OR = 1.31 [95% CI = 1.24 - 1.40, P = 3.78e-18]), lifetime smoking (OR = 2.83 [95% CI = 2.34 - 3.42, P = 6.56e-27]), and systolic blood pressure robustly increased the risk of LRTIs (OR = 1.11 [95% CI = 1.02 - 1.22, P = 1.48e-02]). Conclusion: A region in 15q25.1 was strongly associated with LRTI susceptibility. Reduction of the prevalence of smoking, overweight, obesity, and hypertension may reduce the disease burden of LRTIs. Keywords: body mass index, genome-wide association study, lowerrespiratory tract infection, mendelianrandomization, pneumonia, respiratory infection, smoking

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.

Microbial invasion of the skin and underlying soft tissues, known as skin and soft tissue infections (SSTIs), contribute to considerable burden of disease worldwide (Kaye et al. 2019; Lozano et al. 2012). Knowledge about host factors contributing to SSTI risk is important to prevent the SSTIs. The genetics of SSTI susceptibility remain largely unknown, and the only previously published genome-wide study on SSTIs is a small family-based linkage study that did not identify significant linkage to any genes for erysipelas or cellulitis susceptibility (Hannula-Jouppi et al. 2013).

Funder: Folkehelseinstituttet/Norwegian Institute of Public Health, Funder: Norwegian Ministry of Health and Care Services, Funder: Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research, Funder: Norwegian Ministry of Education and Research, Study questionWhat is the association between BMI and subfertility?Summary answerWe observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization (MR) analysis.What is known alreadyHigh BMI in both women and men is associated with subfertility in observational studies and this relationship is further substantiated by a few small randomized controlled trials of weight reduction and success of assisted reproduction. Women with low BMI also have lower conception rates with assisted reproduction technologies.Study design, size, durationCohort study (the Norwegian Mother, Father and Child Cohort Study), 28 341 women and 26 252 men, recruited from all over Norway between 1999 and 2008.Participants/materials, setting, methodsWomen (average age 30, average BMI 23.1 kg/m2) and men (average age 33, average BMI 25.5 kg/m2) had available genotype data and provided self-reported information on time-to-pregnancy and BMI. A total of 10% of couples were subfertile (time-to-pregnancy ���12 months).Main results and the role of chanceOur findings support a J-shaped association between BMI and subfertility in both sexes using multivariable logistic regression models. Non-linear MR validated this relationship. A 1 kg/m2 greater genetically predicted BMI was linked to 18% greater odds of subfertility (95% CI 5% to 31%) in obese women (���30.0 kg/m2) and 15% lower odds of subfertility (-24% to -2%) in women with BMI

Objectives Bloodstream infection is an important cause of death worldwide. The main objective of this study was to identify genetic loci linked to risk of contracting a bloodstream infection. Design Genome-wide linkage analysis. Setting Population-based, Norwegian cohort, followed between 1995 and 2017. Subjects Among 69,423 genotyped subjects, there were 47 families with two or more second-degree relatives with bloodstream infection in the follow-up period. There were 365 subjects in these families, of which 110 were affected. Interventions None. Measurements and main results The cohort was genotyped using Illumina HumanCoreExome (Illumina, San Diego, CA) arrays. Before linkage analysis, single-nucleotide polymorphisms were pruned and clumped. In nonparametric linkage analysis using an exponential model, we found three loci with a suggestive linkage to bloodstream infection, all on chromosome 4, at 46.6 centimorgan (logarithm of odds, 2.3), 57.7 centimorgan (logarithm of odds, 3.2), and 70.0 centimorgan (logarithm of odds, 2.1). At the peak of the lead region are three genes: TLR10, TLR1, and TLR6. Conclusions Variations in the TLR10/1/6 locus appear to be linked with the risk of contracting a bloodstream infection.

BackgroundSkin and soft tissue infections (SSTIs) are common worldwide, but little is known about the genetic susceptibility and the causal effect of cardiometabolic risk factors. We therefore conducted the first genome-wide association study (GWAS) of SSTIs, with downstream analyses including Mendelian randomization analyses.MethodsThe GWAS was conducted using the UK Biobank as discovery cohort, with 6,107 cases and 399,239 controls, and the Trøndelag Health Study (HUNT) as replication cohort with 1,657 cases and 67,522 controls. Cases and controls were those who had or had not been hospitalized with an SSTI diagnosis, respectively.FindingsOne locus, lead single-nucleotide polymorphism rs3749748 in LINC01184/SLC12A2, was associated with SSTIs in the UK Biobank (odds ratio [OR] 1.19, p-value = 7.6e-16) and replicated in HUNT (OR 1.15, p-value = 6.3e-4). Meta-analysis confirmed the lead variant (OR 1.18, p-value = 4.4e-18), as well as suggested two additional loci close to genome-wide significance (rs2007361 in PSMA1, OR 0.91, p-value = 5.1e-8; and rs78625038 in GAN, OR 1.86, p-value = 5.9e-8). Gene-based association tests identified four genes linked to SSTIs: SLC12A2, PSMA1, GAN, and IL6R. The minor allele of rs3749748 reduced the gene expression of SLC12A2 primarily in monocytes and macrophages. Mendelian randomization analyses showed that increasing body mass index and lifetime smoking habits increased risk of SSTIs.InterpretationLINC0118/SLC12A2 was robustly associated with SSTI incidence and may exert its effect through reduced gene expression in monocytes and macrophages. Reducing tobacco smoking, overweight and obesity in the population may reduce the incidence of SSTIs.

Background. In low-income countries, pediatric emergency care is largely underdeveloped although child mortality in emergency care is more than twice that of adults, and mortality after discharge is high. Aim. We aimed at describing characteristics, triage categories, and post-discharge mortality in a pediatric emergency population in Nepal. Methods. We prospectively assessed characteristics and triage categories of pediatric patients who entered the emergency department (ED) in a local hospital. Patient households were followed-up by telephone interviews at 90 days. Results. The majority of pediatric emergency patients presented with injuries and infections (~40% each). Girls attended ED less frequent than boys. High triage priority categories (orange and red) were strong indicators for intensive care need and for mortality after discharge. Conclusion. The study supports the use and development of a pediatric triage systems in a low-resource general ED setting. We identify a need for interventions that can reduce mortality after pediatric emergency care. Interventions to reduce pediatric emergency disease burden in this setting should emphasize prevention and effective treatment of infections and injuries. Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

In this narrative review, we outline recent evidence relating longitudinal ultrasound (US) measurements to offspring outcomes in the perinatal period and in childhood, with an emphasis on the methodological approaches for describing fetal growth. The utility of longitudinal ultrasonography (US) to measure fetal growth and determine fetal trajectories is valued in both clinical and research environments. Evidence shows that repeated measures of US throughout pregnancy are useful for distinguishing between a growth-restricted and constitutionally small fetus, the former burdened by adverse clinical outcomes. Fetal growth restriction and small for gestational age are not interchangeable terms, although both can exist in the same individual. The application of longitudinal US may have predictive value when determining longer-term health and disease outcomes in offspring born growth-restricted. However, it is important to remember that associations between fetal growth restriction and increased risk for non-communicable diseases are likely modified by postnatal growth.

Background There is a need to develop sustainable emergency health care systems in low-resource settings, but data that analyses emergency health care needs in these settings are scarce. We aimed at assessing presenting complaints (PCs) and post-discharge mortality in a large emergency department population in Nepal. Methods Characteristics of adult patients who entered the emergency department (ED) in a hospital in Nepal were prospectively recorded in the local emergency registry from September 2013 until December 2016. To assess post-ED mortality, patient households were followed-up by telephone interviews at 90 days. Results In 21892 included adults, the major PC categories were injuries (29%), abdominal complaints (23%), and infections (16%). Median age was 40 years and sex distribution was balanced. Among 3793 patients followed at 90 days, 8% had died. For respiratory and cardiovascular PCs, 90-day mortality were 25% and 23%. The highest mortality was in individuals with known chronic lung disease, in this group 32% had died by 90 days of ED discharge, regardless of PC. In women, illiteracy compared to literacy (adjusted odds ratio (aOR) = 7.0, 95% confidence interval (CI) = 2.1-23.6) and being both exposed to tobacco-smoking and traditional cooking stove compared to no smoke (aOR = 2.8, 95% CI = 1.6-4.9) were associated with mortality. The mortality was much higher among family-initiated discharged patients (17%, aOR = 5.4, 95% CI = 3.3-8.9) compared to doctor-initiated discharged (3%). Conclusions Our report suggests that nearly one in ten patients seeking emergency health care died within 90 days. This finding is alarming and novel. Post-discharge studies need to be replicated and appropriate follow-up programs in low-resource settings where primary health care is underdeveloped are urgently needed. © Author(s) 2019. This work is distributed under the Creative Commons Attribution 4.0 License.

BackgroundThe proportion of avoidable hospital deaths is challenging to estimate, but has great implications for quality improvement and health policy. Many studies and monitoring tools are based on selected high-risk populations, which may overestimate the proportion. Mandatory reporting systems, however, under-report. We hypothesise that a review of an unselected sample of hospital deaths will provide an estimate of avoidability in-between the estimates from these methods.MethodsA retrospective case record review of an unselected population of 1000 consecutive non-psychiatric hospital deaths in a Norwegian hospital trust was conducted. Reviewers evaluated to what degree each death could have been avoided, and identified problems in care.ResultsWe found 42 (4.2%) of deaths to be at least probably avoidable (more than 50% chance of avoidability). Life expectancy was shortened by at least 1 year among 34 of the 42 patients with an avoidable death. Patients whose death was found to be avoidable were less functionally dependent compared with patients in the non-avoidable death group. The surgical department had the greatest proportion of such deaths. Very few of the avoidable deaths were reported to the hospital’s report system.ConclusionsAvoidable hospital deaths occur less frequently than estimated by the national monitoring tool, but much more frequently than reported through mandatory reporting systems. Regular reviews of an unselected sample of hospital deaths are likely to provide a better estimate of the proportion of avoidable deaths than the current methods.

To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years.Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25-37, SGA neonates were classified with fetal growth restriction (n=13) or non-fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years.Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, P.05). Although there were no differences between the SGA non-fetal growth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, P.05) and 9 years (96.2 compared with 107.5, P.05) compared with those in the control group. There were some brain volume differences at 15 years between SGA children and those in the control group, but after adjustment for total intracranial volume, age at examination, and sex, there were only significant differences between the SGA fetal growth restriction and control groups for thalamic (17.4 compared with 18.6 cm, P.01) and cerebellar white matter volumes (21.5 compared with 24.3 cm, P.01).Small-for-gestational-age children had lower intelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth.II.

Introduction Natural disasters pose a great challenge to the health systems and individual health facilities. In low-resource settings, disaster preparedness systems are often limited and not been well described. Two devastating earthquakes hit Nepal within a 17-days period in 2015. This study aims to describe the burden and distribution of emergency cases to a local hospital. Methods This is a prospective observational study of patients presenting to a local hospital for a period of 21 days following the earthquake on April 25, 2015. Demographic and clinical information was prospectively registered for all patients in the systematic emergency registry. Systematic telephone interviews were conducted in a random sample of the patients 90 days after admission to the hospital. Results A total of 2,003 emergency patients were registered during the period. The average daily number of emergency patients during the first five days was almost five times higher (n = 150) than the pre-incident daily average (n = 35). The majority of injuries were fractures (58%), 348 (56%) in the lower extremities. A total of 345 surgical procedures were performed and the hospital treated 111 patients with severe injuries related to the earthquake (compartment syndrome, crush injury, and internal injury). Among those with follow-up interviews, over 90% reported that they had been severely affected by the earthquakes; complete house damage, living in temporary shelter, or loss of close family member. Conclusion The hospital experienced a very high caseload during the first days, and the majority of patients needed orthopaedic services. The proportion of severely injured and in-hospital deaths were relatively low, probably indicating that the most severely injured did not reach the hospital in time. The experiences underline the need for robust and easily available local health services that can respond to disasters. © 2018 Giri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.

Objective To evaluate how different levels of increase in maternal blood glucose from a fasting state to 2 h after an oral glucose challenge in late pregnancy are associated with fetal growth, with special emphasis on those with a low increase. Design Prospective cohort study. Subjects We followed 855 women, of whom 70% had an increased risk for carrying lighter babies. Study design and methods Ultrasound was used to estimate fetal growth in gestational weeks 25, 33 and 37. In week 37 the women had a 75-g oral glucose tolerance test, and fasting and 2-h capillary glucose values were recorded with the difference between these two called delta (∆) glucose. Three groups were constructed from the ∆ glucose distribution: Low below the 10th centile; Medium between the 10th and 90th centiles; and High above the 90th centile. Missing data were imputed. Linear and Poisson regression models were applied. Outcome measures Estimated fetal weight, percent deviation from expected fetal weight and anthropometric measures at birth. Results The Low group carried the lightest fetuses and the High group the heaviest. The fetal growth in the Low group deviated increasingly more in a negative direction from week 25 to 37 than in the other groups. Conclusion In a high-risk population, a positive relation between ∆ glucose and fetal growth was found. The Low group demonstrated impaired growth. More attention should be paid to pregnant women with an insufficient increase in glucose after a glucose challenge. Future studies should challenge our findings in high-risk and low-risk populations.

available from 2018-02-01 Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight