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Introduction The number of adolescents seeking professional help for depression is increasing and, despite advances in treatment, large unmet treatment needs remain. In the current protocol, we describe the design and methodology of a randomised controlled trial (RCT) to evaluate the clinical efficacy of two forms of internet-delivered behavioural activation (I-BA), with and without therapist support, in reducing depressive symptoms, compared with treatment as usual (TAU). Secondary objectives include examining the 12-month maintenance of the treatment effects and conducting a health economic evaluation of the interventions.Methods and analysis In this single-blinded RCT, we aim to include 215 participants aged 13–17 years with mild to moderate depression who will be randomised (1:1:1 ratio) to 10 weeks of either therapist-guided or self-guided I-BA, or TAU provided by regular mental health clinics. Data will be collected at baseline, weekly for the initial 10 weeks, post-treatment and at 3 and 12-month follow-ups. The primary endpoint is the 3-month follow-up. The primary outcome is blinded clinician-rated severity of depressive symptoms, measured by the Children’s Depression Rating Scale-Revised. Treatment response is defined as a score of ‘Much improved’ or ‘Very much improved’ on the Clinical Global Impression-Improvement Scale, administered at the primary endpoint. Outcome assessors will be blinded to treatment conditions at all assessment points. A health economic evaluation of I-BA will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up).Ethics and dissemination Ethical approval was obtained from the Swedish Ethical Review Authority in June 2021. The final participant was enrolled on 3 May 2024 and expected to reach the primary endpoint by November 2024. The results of this study will be disseminated through publication in peer-reviewed journals, presented at conferences and communicated to healthcare providers and the public.Trial registration number NCT04977856.

BackgroundSexual Interest in Children (SIC) is a major risk factor for sexual offending, yet clinical trials are sparse. The present protocol outlines a randomized controlled trial (RCT) that aims to investigate the effectiveness of fluoxetine and Cognitive Behavioral Therapy (CBT) in help-seeking men with SIC.MethodsAdult men contacting the Swedish telephone helpline PrevenTell are screened for inclusion and invited to further assessment on site. One hundred and eleven men with SIC (defined as DSM-5 pedophilic disorder or hebephilia) will be randomized (1:1:1 ratio) to receive one of three interventions for 14 weeks: (1) an internet-administered psychoeducational program (iPP), (2) iPP and the addition of fluoxetine 20-40 mg or (3) iPP and the addition of internet-administered CBT (iCBT). Exclusion criteria include severe psychiatric illness, contraindicating treatment and an elevated risk of committing hands-on sexual offences. Symptom intensity is assessed at baseline, pre-treatment, every other week for 12 weeks, and post treatment. The primary outcome measure is the Sexual Interest in Children: Current Assessment Scale (SIC: CAS) that quantifies sexual behaviors associated with SIC as well as perceived distress and impairment. Secondary outcomes include measures of dynamic risk-factors for committing sexual offences.ResultsThe data collected during the initial 20 months of recruitment were analyzed to predict the required number of individuals to be screened and estimate the probable length of the data collection phase. As of March 2022 to November 2023, 146 men have called PrevenTell and disclosed a sexual interest in minors. Following pre-screening, 110 men were excluded from participation in the trial. Current SSRI therapy was the primary reason for exclusion (n = 24; 22%), followed by an elevated risk of committing hands-on sexual offences (n = 14; 13%). Among the 31 men who underwent the screening procedure on site, 26 were allocated to either iPP, iPP+fluoxetine, or iPP+iCBT. The recruitment rate indicates that the trial will be concluded within the pre-estimated timeframe.DiscussionThis is the first RCT of treatment with SSRI and iCBT in a population of help-seeking men with SIC. The significance of this trial and its methodological strengths and limitations are discussed.

BackgroundIncreased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited.MethodsA nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020.Results53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26).ConclusionNo association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.

Abstract High‐content image‐based cell phenotyping provides fundamental insights into a broad variety of life science disciplines. Striving for accurate conclusions and meaningful impact demands high reproducibility standards, with particular relevance for high‐quality open‐access data sharing and meta‐analysis. However, the sources and degree of biological and technical variability, and thus the reproducibility and usefulness of meta‐analysis of results from live‐cell microscopy, have not been systematically investigated. Here, using high‐content data describing features of cell migration and morphology, we determine the sources of variability across different scales, including between laboratories, persons, experiments, technical repeats, cells, and time points. Significant technical variability occurred between laboratories and, to lesser extent, between persons, providing low value to direct meta‐analysis on the data from different laboratories. However, batch effect removal markedly improved the possibility to combine image‐based datasets of perturbation experiments. Thus, reproducible quantitative high‐content cell image analysis of perturbation effects and meta‐analysis depend on standardized procedures combined with batch correction.

Objective: To comprehensively assess the extent to which the decline in cardiorespiratory fitness (CRF) with age differs between sexes. Participants and Methods: This study used data from the Aerobics Center Longitudinal Study, conducted between September 1974 and August 2006, consisting primarily of White adults from middle-to-upper socioeconomic strata restricted to adults without type 2 diabetes mellitus (33,742 men and 9,415 women). Quantile regression models were used to estimate the differences in age-associated changes in CRF between the sexes, estimated using a maximal treadmill test. Results: For adults aged up to 45 years, significant differences in slopes relating to age and CRF between men and women were observed for all adjusted percentiles of CRF other than the 90th percentile; women reported significantly greater declines in CRF per year. For those aged 45-60 years and those older than 60 years, no significant differences in age-related declines in CRF were observed between the sexes. Conclusion: This study found that compared with men, the onset of decline in CRF was found to occur earlier and at lower CRF percentiles in women. This is of particular concern, given that compared with men, women already tend to have lower CRF levels. These findings suggest that maintaining the levels of physical activity sufficient to maintain moderate-to-high levels of fitness is particularly important for women earlier during adulthood.

Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design, setting, and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45–75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer.

Main objectiveSickness absence duration for shoulder lesion patients is difficult to prognosticate, and scientific evidence for the sick-listing practice is lacking. Our objective was to develop a clinically implementable prediction model for the duration of a sickness absence spell due to shoulder lesions.MethodsAll new sickness absence spells due to shoulder lesions (ICD-10-code: M75) issued in the period January 2010-June 2012 that were longer than 14 days were identified through the nationwide sickness absence insurance register. Information on predictors was linked from four other nationwide registers. Piecewise-constant hazards regression models were fitted to predict duration of sickness absence. The model was developed and validated using split sample validation. Variable selection was based on log-likelihood loss ranking when excluding a variable from the model. The model was evaluated using calibration plots and the c-statistic.Results20 049 sickness absence spells were identified, of which 34% lasted >90 days. Predictors included in the model were age, sex, geographical region, occupational status, educational level, birth country, specialized healthcare at start of the spell, number of sickness absence days in the last 12 months, and specialized healthcare the last 12 months, before start date of the index sickness absence spell. The model was satisfactorily specified and calibrated. Overall c-statistic was 0.54 (95% CI 0.53-0.55). C-statistic for predicting durations >90, >180, and >365 days was 0.61, 0.66, and 0.74, respectively.SignificanceThe model can be used to predict the duration of sickness absence due to shoulder lesions. Covariates had limited predictive power but could discriminate the very long sickness absence spells from the rest.

Abstract Background Treatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial’s primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention. Methods In this single-blind superiority RCT, 220 participants (9–17 years) with TS/CTD throughout Sweden will be randomised to 10–12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale – Total Tic Severity Score. Treatment response is operationalised as scores of “Very much improved” or “Much improved” on the Clinical Global Impression – Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses. Discussion Participant recruitment started on 26 April 2019 and finished on 9 April 2021. The total number of included participants was 221. The final participant is expected to reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint. Trial registration ClinicalTrials.gov NCT03916055 . Registered on 16 April 2019.

Abstract The objective was to evaluate the sequentially updated predictive capacity for preeclampsia during pregnancy, using multivariable longitudinal models including data from antenatal care. This population-based cohort study in the Stockholm-Gotland Counties, Sweden, included 58,899 pregnancies of nulliparous women 2008–2013. Prospectively collected data from each antenatal care visit was used, including maternal characteristics, reproductive and medical history, and repeated measurements of blood pressure, weight, symphysis-fundal height, proteinuria, hemoglobin and blood glucose levels. We used a shared-effects joint longitudinal model including all available information up until a given gestational length (week 24, 28, 32, 34 and 36), to update preeclampsia prediction sequentially. Outcome measures were prediction of preeclampsia, preeclampsia with delivery

Objective: To assess the extent to which the established age-related decline in cardiorespiratory fitness (CRF) is augmented in adult men with type 2 diabetes mellitus (T2DM). Participants and Methods: This study used data from the Aerobics Center Longitudinal Study, conducted between September 18, 1974, and August 3, 2006, in primarily non-Hispanic white, middle-to-upper class adults. The analyses were restricted to adult men with complete data on age, CRF, and T2DM (35,307 participants). Quantile regression models were used to estimate age-related differences in CRF, estimated using a maximal treadmill test, between persons with and without T2DM. Smoking status and birth cohort served as covariates. Results: Age-related declines in CRF were observed in men with and without T2DM. For men younger than 60 years, at low-mid percentiles of the CRF distribution the magnitude of the age-related decline in CRF was significantly higher (P-values=.00, .02) in men with T2DM than in those without T2DM. At upper percentiles, the decline with age between the 2 groups was virtually identical. Significant declines in CRF in men 45 years or younger were observed only at high levels of CRF for those without T2DM and at low levels of CRF for those with T2DM (P-values .00, .04). Conclusion: This study reported that men younger than 60 years with T2DM at the low-mid CRF percentiles experience an accelerated age-related decline in CRF. Men younger than 60 years with T2DM exhibiting high levels of CRF experienced a decline in CRF comparable to men without T2DM. This study highlights the importance of incorporating sufficient levels of exercise or activity to maintain high CRF in men with T2DM.

Abstract Background Predicting the duration of sickness absence (SA) among sickness absent patients is a task many sickness certifying physicians as well as social insurance officers struggle with. Our aim was to develop a prediction model for prognosticating the duration of SA due to knee osteoarthritis. Methods A population-based prospective study of SA spells was conducted using comprehensive microdata linked from five Swedish nationwide registers. All 12,098 new SA spells > 14 days due to knee osteoarthritis in 1/1 2010 through 30/6 2012 were included for individuals 18–64 years. The data was split into a development dataset (70 %, nspells =8468) and a validation data set (nspells =3690) for internal validation. Piecewise-constant hazards regression was performed to prognosticate the duration of SA (overall duration and duration > 90, >180, or > 365 days). Possible predictors were selected based on the log-likelihood loss when excluding them from the model. Results Of all SA spells, 53 % were > 90 days and 3 % >365 days. Factors included in the final model were age, sex, geographical region, extent of sickness absence, previous sickness absence, history of specialized outpatient healthcare and/or inpatient healthcare, employment status, and educational level. The model was well calibrated. Overall, discrimination was poor (c = 0.53, 95 % confidence interval (CI) 0.52–0.54). For predicting SA > 90 days, discrimination as measured by AUC was 0.63 (95 % CI 0.61–0.65), for > 180 days, 0.69 (95 % CI 0.65–0.71), and for SA > 365 days, AUC was 0.75 (95 % CI 0.72–0.78). Conclusion It was possible to predict patients at risk of long-term SA (> 180 days) with acceptable precision. However, the prediction of duration of SA spells due to knee osteoarthritis has room for improvement.

Abstract Background Women’s return to work after diagnosis of breast cancer (BC) is becoming more prevalent. However, register-based national investigation on sickness absence (SA) and disability pension (DP) in BC women is lacking. The aim of the study was to explore SA and DP before and after a first BC diagnosis and the possibility to predict new cancer-related SA by using disease-related and sociodemographic factors. Methods A longitudinal register study of the 3536 women in Sweden aged 19–64 with a first BC diagnosis in 2010 was conducted by linkage of five nationwide registers. Particularly, detailed information on SA and DP was obtained from the National Social Insurance Agency. Descriptive statistics on SA and DP 2 years before through 3 years after the BC diagnosis were performed. The risk of having a new SA spell due to BC or BC-related diagnoses was modeled using logistic regression. Results The proportion of women with SA increased during the year following the BC diagnosis date and declined over the next 2 years to proportions before diagnosis. At the time of BC diagnosis, half of the women began a new SA spell > 14 days with cancer, cancer-related, or mental diagnosis. Disease-related and sociodemographic factors including occupational sector, living area, age, cancer stage, educational level, and number of previous SA days showed statistical significance (p

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death. Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM–coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation. Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

Background Systolic blood pressure (SBP) after endovascular thrombectomy (EVT) for large artery occlusive stroke is dynamic, requiring adaptable early prediction tools for improving outcomes. We investigated if post-EVT SBP course was associated with outcomes.Methods EVT-treated patients who had a stroke at Karolinska University Hospital, Stockholm, Sweden, were included in the study during 12 February 2018–11 February 2020. SBP was recorded during the first 24 hours after EVT. Primary outcome was functional independence defined by a Modified Rankin Scale score of 0–2 at 3 months. Secondary outcomes were death by 3 months, symptomatic intracranial haemorrhage and any intracranial haemorrhage. Patients with favourable outcomes were used as a reference SBP course in mixed linear effects models and compared with SBP courses of patients with unfavourable outcomes using the empirical best linear unbiased predictor, measuring deviations from the reference SBP course using the random effects. We tested model predictive stability for SBP measurements of only 18, 12 or 6 hours after EVT.Results 374 patients were registered, with mean age 71, median NIHSS score of 15, and 53.2% men. Deviating from a linear SBP course starting at 130 mm Hg and decreasing to 123 mm Hg at 24 hours after EVT was associated with lower chances of functional independence (adjusted OR 0.53, 95% CI 0.29 to 0.88, for reaching either 99 or 147 mm Hg at 24 hours after EVT). All SBP course models for the remaining outcomes did not show statistical significance. Functional independence models showed stable predictive values for all time periods.Conclusion Deviating from a linear SBP course was associated with lower chances of 3-month functional independence.

Abstract Acute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment. Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy. Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.

Abstract Introduction Research on picky eating in childhood obesity treatment is limited and inconsistent, with various instruments and questions used. This study examines the role of picky eating in a randomized controlled obesity intervention for preschoolers using subscales from two instruments: The Child Eating Behavior Questionnaire (CEBQ) and the Lifestyle Behavior Checklist (LBC). Method The study includes 130 children (mean age 5.2 years (SD 0.7), 54% girls, mean Body Mass Index (BMI) z-score 2.9 (SD 0.6)) and their parents (nearly 60% of non-Swedish background, 40% with university degree). Families were randomized to a parent-group treatment focusing on evidence-based parenting practices or to standard treatment focusing on lifestyle changes. The children’s heights and weights (BMI z-score) were measured at baseline, and at 3, 6 and 12 months post baseline. At these time-points, picky eating was reported by parents using the CEBQ (Food Fussiness scale, 6 items) and 5 items from the LBC. Child food intake was reported with a Food Frequency Questionnaire (FFQ). Pearson correlation was used to study associations between baseline picky eating and baseline BMI z-scores and food intake. Mixed effects models were used to study associations between the two measurements of picky eating and changes in picky eating, to assess the effects of changes in picky eating on BMI z-scores, and to evaluate baseline picky eating as a predictor of changes in BMI z-scores. Results Neither the standard treatment nor the parent-group treatment reduced the degree of picky eating (measured with CEBQ or LBC). Baseline picky eating measured with the CEBQ was associated with a lower BMI z-score and lower intake of vegetables. Children with a higher degree of picky eating at baseline (measured with the CEBQ) displayed a lower degree of weight loss. When degree of picky eating was examined, for 25% of the children, the CEBQ and the LBC yielded diverging results. Conclusions Baseline picky eating may weaken the effectiveness of obesity treatment, and assessments should be conducted before treatment to adjust the treatment approach. Different measurements of picky eating may lead to different results. The CEBQ seems more robust than the LBC in measuring picky eating. Trial registration Clinicaltrials.gov, NCT01792531. Registered 15 February 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01792531

Abstract Background Cognitive impairment and psychological distress are common in intensive care unit (ICU) survivors. Early identification of affected individuals is important, so intervention and treatment can be utilized at an early stage. Cognitive Failures Questionnaire (CFQ) is commonly used to screen for subjective cognitive function, but it is unclear whether CFQ scores correlate to objective cognitive function in this population. Methods Between 2014 and 2018, 100 ICU survivors aged 18–70 years from the general ICU at the Karolinska University Hospital, Solna, were included in the study. Out of these, 58 patients completed follow-up at 3 months after ICU discharge, 51 at 6 months, and 45 at 12 months. Follow-up included objective cognitive function testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and subjective cognitive function testing with the self-rating Cognitive Failures Questionnaire (CFQ), as well as psychological self-rating with the Post-Traumatic Stress Symptoms Scale-10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS). Results The prevalence of cognitive impairment as measured by four selected CANTAB tests was 34% at 3 months after discharge, 18% at 6 months, and 16% at 12 months. There was a lack of significant correlation between CANTAB scores and CFQ scores at 3 months (r = − 0.134–0.207, p > 0.05), at 6 months (r = − 0.106–0.257, p > 0.05), and at 12 months after discharge (r = − 0.070–0.109, p > 0.05). Correlations between CFQ and PTSS-10 scores and HADS scores, respectively, were significant over the follow-up period (r = 0.372–0.710, p ≤ 0.001–0.023). In contrast, CANTAB test scores showed a weak correlation with PTSS-10 and HADS scores, respectively, at 3 months only (r = − 0.319–0.348, p = 0.008–0.015). Conclusion We found no clinically relevant correlation between subjective and objective cognitive function in this cohort of ICU survivors, while subjective cognitive function correlated significantly with psychological symptoms throughout the follow-up period. Treatment and evaluation of ICU survivors’ recovery need to consider both subjective and objective aspects of cognitive impairment, and subjective reports must be interpreted with caution as an indicator of objective cognitive function.

Malaria is a potentially life-threatening disease with approximately half of the world's population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27- memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.

Adults with type 2 diabetes mellitus tend to exhibit an increased level of central adiposity, augmenting their risk of further non-communicable diseases (NCDs). Importantly, consistent evidence demonstrates a significant, negative association between cardiorespiratory fitness (CRF) and waist circumference (WC). However, no previous studies have investigated differences in these CRF-related reductions in WC between adults with and without diabetes.This study used data from the Aerobic Center for Longitudinal Studies, conducted between 1970 and 2006 among predominately Non-Hispanic White, middle-to-upper class adults in Texas. Quantile regression models were used to estimate CRF-related differences in WC between persons with and without diabetes. Age, height, smoking status and birth cohort served as covariates. The analytic sample included 45901 adults.Significantly larger reductions in WC were observed among adults with diabetes as compared to without diabetes across all WC percentiles. Among males, high CRF levels were associated with significant reductions, as compared to their low-fit counterparts, in WC as large as 21.9 cm for adults without diabetes and as large as 27 cm for adults with diabetes. Among females, high CRF levels were associated with significant reductions, as compared to their low-fit counterparts, in WC as large as 22.3 and 30.0 cm for adults without and with diabetes, respectively.This study demonstrated that higher CRF is associated with significant reductions in WC, with greater magnitudes found among adults with diabetes, especially among the most centrally obese, highlighting the necessity of exercise prescription in this clinical population potentially leading to lower risks of future NCDs.

OBJECTIVE: The aim of this study was to assess the potential to reduce kidney function damage during the implementation of a water, rest, shade (WRS) and efficiency intervention program among sugarcane workers. METHODS: A WRS intervention program adapted from the US Occupational Safety and Health Administration (OSHA) coupled with an efficiency program began two months into the 5-month harvest. One of the two groups of workers studied was provided with portable water reservoirs, mobile shaded tents, and scheduled rest periods. Health data (anthropometric and questionnaires), blood, and urine were collected at baseline and at three subsequent times over the course of the harvest. Daily wet bulb globe temperatures (WBGT) were recorded. RESULTS: Across a working day there were changes in biomarkers indicating dehydration (urine osmolality) and serum albumin and reduced estimated glomerular filtration rate (eGFR). Cross-shift eGFR decrease was present in both groups; -10.5 mL/min/1.73m2 [95% confidence interval (95% CI) -11.8– -9.1], but smaller for the intervention group after receiving the program. Decreased eGFR over the 5-month harvest was seen in both groups: in the one receiving the intervention -3.4 mL/min/1.73m^2 (95% CI -5.5– -1.3) and in the other -5.3 (95% CI -7.9– -2.7). The decrease appeared to halt after the introduction of the intervention in the group receiving the program. CONCLUSION: A WRS and efficiency intervention program was successfully introduced for workers in sugarcane fields and appears to reduce the impact of heat stress on acute and over-harvest biomarkers of kidney function. Further research is needed to determine whether biomarker changes predict reduced risk of chronic kidney disease in this type of work.

Abstract Background Many intensive care unit (ICU) survivors develop psychological problems and cognitive impairment. The relation between sepsis, delirium, and later cognitive problems is not fully elucidated, and the impact of psychological symptoms on cognitive function is poorly studied in ICU survivors. The primary aim of this study was to examine the relationship between sepsis, ICU delirium, and later self-rated cognitive function. A second aim was to investigate the association between psychological problems and self-rated cognitive function 3 months after the ICU stay. Methods Patients staying more than 24 h at the general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden, were screened for delirium with the Confusion Assessment Method-ICU (CAM-ICU) during their ICU stay. Sepsis incidence and severity were recorded. Three months later, 216 patients received the Cognitive Failures Questionnaire (CFQ), Hospital Anxiety and Depression Scale (HADS), and Post-Traumatic Stress Symptoms-10 (PTSS-10) questionnaires via postal mail. Results One hundred twenty-five patients (60%) responded to all questionnaires. Among respondents, the incidence of severe sepsis or septic shock was 42%. The overall incidence of delirium was 34%. Patients with severe sepsis/septic shock had a higher incidence of delirium, with an odds ratio (OR) of 3.7 (95% confidence interval (CI), 1.7–8.1). Self-rated cognitive problems 3 months post-ICU were found in 58% of the patients. We did not find any association between sepsis or delirium and late self-rated cognitive function. However, there was a correlation between psychological symptoms and self-rated cognitive function, with the strongest correlation between PTSS-10 scores and CFQ scores (r = 0.53; p

Abstract Background A majority of patients survive their episode of critical illness but up to 30% of patients suffer from psychological problems such as post-traumatic stress, anxiety and depression in the year after intensive care unit (ICU) stay. A method to identify discharged patients at risk for adverse psychological outcome would be helpful in the triage for ICU follow-up and could enable early intervention. The aim of this study was to evaluate whether early screening with validated questionnaires after ICU discharge can identify patients at risk for symptoms of post-traumatic stress, anxiety and depression 3 months after ICU stay. Methods We performed a prospective observational cohort study in the general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden. All adult patients surviving ≥ 24 hours in the ICU in a 9-month period were eligible for inclusion. Patients with mental disability, serious auditory and visual disorder, aphasia or who were unable to understand Swedish were excluded. One hundred and thirty-two patients were included and visited by a follow-up nurse within 1 week after ICU discharge. The Hospital Anxiety and Depression Scale (HADS) and the Post-Traumatic Stress Symptoms Checklist-10 (PTSS-10) were administered. Three months after ICU discharge the patients received the same questionnaires by postal mail. We assessed the predictive values of the questionnaires using the area under the receiver operating characteristic curve (AUROC). For correlation calculations, we used Spearman’s rank correlation coefficient. Negative and positive predictive values for each questionnaire were calculated. Results Eighty-two patients returned the follow-up questionnaires. We found correlation between early and late scores and reasonable predictive precision regarding 3-month outcomes, with an AUROC of 0.90 for PTSS-10 part B, 0.80 for the HADS anxiety subscale and 0.75 for the HADS depression subscale. Conclusions Symptoms of post-traumatic stress, anxiety and depression assessed 1 week after ICU stay correlate with 3-month psychological outcome. The HADS and PTSS-10 may be useful aids to identify ICU survivors at high risk for clinically significant symptoms of post-traumatic stress, anxiety and depression 3 months post ICU stay.

Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier. The most abundant plasticizers in preschool dust were the phthalates di-isononyl phthalate (DiNP) and di-(2-ethylhexyl) phthalate (DEHP) with geometric mean levels of 450 and 266 μg/g dust, respectively, and the non-phthalate plasticizers bis(2-ethylhexyl) terephthalate (DEHT) and diisononylcyclohexane-1,2-dicarboxylate (DiNCH) found at 105 and 73 μg/g dust, respectively. The levels of several substitute plasticizers were higher in newer preschools, whereas the levels of the strictly regulated phthalate di-n-butyl phthalate (DnBP) were higher in older preschools. The presence of foam mattresses and PVC flooring in the sampling room were associated with higher levels of DiNP in dust. Children's exposure from preschool dust ingestion was below established health based reference values and the estimated exposure to different phthalates and BPA via preschool dust ingestion accounted for 2–27% of the total exposure. We found significantly lower urinary levels of BPA and metabolites of strictly regulated phthalates, but higher levels of DiNP metabolites, in urine from the children in this study compared to the children who provided urine samples fifteen years earlier. Keywords: Dust, Preschool, Exposure assessment, Plasticizer, Phthalate, Bisphenol A

OBJECTIVE:To evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women. DESIGN AND SETTING:A population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008-13 in the Stockholm-Gotland Counties in Sweden. METHODS:Maternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine Foundation model including maternal factors and mean arterial pressure), 2) backward selection starting from the full suite of variables, and 3) a Random forest model using the same candidate variables. The performance of the British National Institute for Health and Care Excellence (NICE) binary risk classification guidelines for preeclampsia was also evaluated. The outcome measures were diagnosis of preeclampsia with delivery

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

Unintentional weight loss has been observed among Parkinson’s disease (PD) patients. Changes in energy intake (EI) and eating behavior, potentially caused by fine motor dysfunction and eating-related symptoms, might contribute to this. The primary aim of this study was to investigate differences in objectively measured EI between groups of healthy controls (HC), early (ESPD) and advanced stage PD patients (ASPD) during a standardized lunch in a clinical setting. The secondary aim was to identify clinical features and eating behavior abnormalities that explain EI differences. All participants (n = 23 HC, n = 20 ESPD, and n = 21 ASPD) went through clinical evaluations and were eating a standardized meal (200 g sausages, 400 g potato salad, 200 g apple purée and 500 mL water) in front of two video cameras. Participants ate freely, and the food was weighed pre- and post-meal to calculate EI (kcal). Multiple linear regression was used to explain group differences in EI. ASPD had a significantly lower EI vs. HC (−162 kcal, p < 0.05) and vs. ESPD (−203 kcal, p < 0.01) when controlling for sex. The number of spoonfuls, eating problems, dysphagia and upper extremity tremor could explain most (86%) of the lower EI vs. HC, while the first three could explain ~50% vs. ESPD. Food component intake analysis revealed significantly lower potato salad and sausage intakes among ASPD vs. both HC and ESPD, while water intake was lower vs. HC. EI is an important clinical target for PD patients with an increased risk of weight loss. Our results suggest that interventions targeting upper extremity tremor, spoonfuls, dysphagia and eating problems might be clinically useful in the prevention of unintentional weight loss in PD. Since EI was lower in ASPD, EI might be a useful marker of disease progression in PD.

Background. Renal dysfunction after acute kidney injury (AKI) is common, potentially modifiable, but poorly understood. Acute kidney disease (AKD) describes renal dysfunction 7 to 90 days after AKI and is determined by percentage change in creatinine from baseline. Chronic kidney disease (CKD) is defined as the estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 persisting for more than 90 days. We compared CKD incidence using both creatinine- and cystatin C-based GFR with AKD incidence at 90 days in AKI survivors. Methods. A prospective cohort study was conducted in a Swedish intensive care unit (ICU) between 2008 and 2010. We included AKI patients alive at 90 days. We excluded patients 100 years, death before follow-up, CKD prior to admission, and follow-up before 60 days or beyond 270 days. Creatinine and cystatin C were measured at 90 days and converted to eGFR (mL/min/1.73 m2). Results. We included 274 patients. At 90-day follow-up, the median creatinine eGFR (MDRD) was 81.6 (IQR 58.6–106.8) and median cystatin C eGFR was 51.5 (IQR 35.8–70.7). The incidence of CKD (eGFR

BACKGROUND:Mitogen activated-protein kinase pathway inhibitors (MAPKis) improve treatment outcome in patients with disseminated BRAFV600 mutant cutaneous malignant melanoma (CMM) but responses are of limited duration due to emerging resistance. Although extensive research in mechanisms of resistance is being performed, predictive biomarkers for durable responses are still lacking. We used miRNA qPCR to investigate if different levels of extracellular microvesicle microRNA (EV miRNA) in matched plasma samples collected from patients with metastatic IV BRAFV600 mutated CMM before, during and after therapy with MAPKis could serve as predictive biomarkers. MATERIALS AND METHODS:EV miRNAs were extracted from plasma samples from 28 patients collected before and during therapy, measured by quantitative PCR-array and correlated to therapy outcome. RESULTS:Increased levels of EV let-7g-5p during treatment compared to before treatment (EV let-7g-5p_delta) were associated with better disease control with MAPKis (odds ratio 8568.4, 95% CI = 4.8-1.5e+07, P = 0.000036). Elevated levels of EV miR-497-5p during therapy were associated with prolonged progression free survival (PFS) (hazard ratio = 0.27, 95% CI = 0.13-0.52, P

Background: Lithium, used for treating bipolar disease, crosses freely the placenta and is classified as teratogenic. It is unclear to what extent environmental lithium exposure may affect fetal growth and development. Objectives: To elucidate potential effects of lithium exposure through drinking water during pregnancy on fetal size. Methods: We developed a prospective population-based mother–child cohort (N = 194) in an area with highly varying drinking water lithium concentrations (5-1600 μg/L) in northern Argentinean Andes. Blood and urinary lithium concentrations (sampled repeatedly during pregnancy) were measured using inductively coupled plasma mass spectrometry. We measured fetal size by ultrasound in second and third trimesters, and weight, length and head circumference at birth. Multivariable models were used to examine associations between lithium exposure (continuous and in tertiles) and fetal size measures. Results: Lithium in maternal blood (median 25; range 1.9–145 μg/L) and urine (1645; 105–4600 μg/L) was inversely associated (apparently linearly) with all fetal measures (body, head and femur) in the second trimester, and with birth length (β −0.53 cm per 25 μg/L increase in blood lithium, 95%CI −1.0; −0.052). An increase of 100 μg/L in blood was associated with 2 cm shorter newborns (about one standard deviation). Conclusions: Lithium exposure through drinking water was associated with impaired fetal size and this seemed to be initiated in early gestation. Further studies are warranted to confirm causality and to understand the mechanisms. If confirmed, these findings have public health relevance and emphasize the need for more data on lithium concentrations in drinking water, including bottled water. Keywords: Birth weight, Fetal size, Early-life exposure, Lithium, Water pollutants

Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (

Abstract In 2013, EFSA published a comprehensive systematic review of epidemiological studies published from 2006 to 2012 investigating the association between pesticide exposure and many health outcomes. Despite the considerable amount of epidemiological information available, the quality of much of this evidence was rather low and many limitations likely affect the results so firm conclusions cannot be drawn. Studies that do not meet the ‘recognised standards’ mentioned in the Regulation (EU) No 1107/2009 are thus not suited for risk assessment. In this Scientific Opinion, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to assess the methodological limitations of pesticide epidemiology studies and found that poor exposure characterisation primarily defined the major limitation. Frequent use of case–control studies as opposed to prospective studies was considered another limitation. Inadequate definition or deficiencies in health outcomes need to be avoided and reporting of findings could be improved in some cases. The PPR Panel proposed recommendations on how to improve the quality and reliability of pesticide epidemiology studies to overcome these limitations and to facilitate an appropriate use for risk assessment. The Panel recommended the conduct of systematic reviews and meta‐analysis, where appropriate, of pesticide observational studies as useful methodology to understand the potential hazards of pesticides, exposure scenarios and methods for assessing exposure, exposure–response characterisation and risk characterisation. Finally, the PPR Panel proposed a methodological approach to integrate and weight multiple lines of evidence, including epidemiological data, for pesticide risk assessment. Biological plausibility can contribute to establishing causation.

Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.

There are concerns that the reported association of ambient fine particulate matter (PM2.5) with mortality might be a mixture of PM2.5 and weather conditions. We evaluated the effects of extreme weather conditions and weather types on mortality as well as their interactions with PM2.5 concentrations in a time series study. Daily non-accidental deaths, individual demographic information, daily average PM2.5 concentrations and meteorological data between 2012 and 2014 were obtained from Shanghai, China. Days with extreme weather conditions were identified. Six synoptic weather types (SWTs) were generated. The generalized additive model was set up to link the mortality with PM2.5 and weather conditions. Parameter estimation was based on Bayesian methods using both the Jeffreys' prior and an informative normal prior in a sensitivity analysis. We estimate the percent increase in non-accidental mortality per 10 μg/m3 increase in PM2.5 concentration and constructed corresponding 95% credible interval (CrI). In total, 336,379 non-accidental deaths occurred during the study period. Average daily deaths were 307. The results indicated that per 10 μg/m3 increase in daily average PM2.5 concentration alone corresponded to 0.26-0.35% increase in daily non-accidental mortality in Shanghai. Statistically significant positive associations between PM2.5 and mortality were found for favorable SWTs when considering the interaction between PM2.5 and SWTs. The greatest effect was found in hot dry SWT (percent increase = 1.28, 95% CrI: 0.72, 1.83), followed by warm humid SWT (percent increase = 0.64, 95% CrI: 0.15, 1.13). The effect of PM2.5 on non-accidental mortality differed under specific extreme weather conditions and SWTs. Environmental policies and actions should take into account the interrelationship between the two hazardous exposures.

Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002–2011 was 57.5±3.4%, but 44.7±3.2% (P

BACKGROUND:Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. METHODS:We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. FINDINGS:Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6-6.0 and 2.8-5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25-50% and 11-16% of excess population attributable risk, respectively (p

Background. Poor nutrition, lack of physical activity, and obesity in children have important public health implications but, to date, their effects have not been studied in the growing population of children in Sweden with immigrant parents. Methods. We estimated the association between parental migration background and nutrition, physical activity, and weight in 8-year-old children born in Stockholm between 1994 and 1996 of immigrants and Swedish parents (n=2589). Data were collected through clinical examination and questionnaires filled out by parents. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using multivariable logistic regression. Results. Children of immigrants complied more closely with Nordic Nutrition Recommendations compared with those of Swedes (OR = 1.35, 95% CI 1.11–1.64). They had higher intake of dietary fibre, vitamins C, B6, and E, folic acid, and polyunsaturated fatty acids (omega-3 and omega-6) reflecting higher consumption of foods of plant origin, but lower intake of vitamins A and D, calcium, and iron reflecting lower consumption of dairy products. Children of immigrants had higher intake of sucrose reflecting higher consumption of sugar and sweets. Furthermore, these children had a higher risk of having low physical activity (OR = 1.31, 95% CI 1.06–1.62) and being overweight (OR = 1.33, 95% CI 1.06–1.65) compared with children of Swedish parents. The odds of having low physical activity and being overweight were even higher in children whose parents were both immigrants. A low level of parental education was associated with increased risk of low physical activity regardless of immigration background. Conclusions. Culturally appropriate tools to capture the diverse range of ethnic foods and other lifestyle habits are needed. Healthcare professionals should be aware of the low levels of physical activity, increased weight, and lack of consumption of some important vitamins among children of immigrants.

Larvae of the Northern pine processionary moth (Thaumetopoea pinivora, TP) carry microscopic needles (setae), which by penetrating skin and mucous membranes, may cause inflammatory/immune derived symptoms in man. In the present study the stimulatory effects of setae on human blood lymphocytes in vitro was investigated. Blood mononuclear cells were separated from venous blood or buffy coat of ten healthy individuals, six previously exposed to setae and four with no known exposure. Lymphoproliferation was measured as uptake of 3H-thymidine. Setae were prepared from TP larvae. Setae and saline setae extracts stimulated proliferation of T-lymphocytes in the presence of monocytic cells. Stimulation was pronounced in cells from persons who had been exposed to setae, and weak in cells from non-exposed donors. Chitin also induced lymphocyte proliferation in most donors, but to a lesser extent and independently of donor's previous exposure to setae. In conclusion, setae contain molecules that in the presence of monocytes activate human T-lymphocytes to proliferation. The antigenic nature of stimulatory molecules was supported by the significantly stronger lymphocyte response in persons previously exposed to setae than in non-exposed donors. The nature of such molecules remains to be defined.

In 2010, cancer deaths accounted for more than 15% of all deaths worldwide, and this fraction is estimated to rise in the coming years. Increased cancer mortality has been observed in immigrant populations, but a comprehensive analysis by country of birth has not been conducted. We followed all individuals living in Sweden between 1961 and 2009 (7,109,327 men and 6,958,714 women), and calculated crude cancer mortality rates and age-standardized rates (ASRs) using the world population for standardization. We observed a downward trend in all-site ASRs over the past two decades in men regardless of country of birth but no such trend was found in women. All-site cancer mortality increased with decreasing levels of education regardless of sex and country of birth (p for trend

BACKGROUND: Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring. OBJECTIVES: To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics. METHODS: A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data. RESULTS: We observed a significant BMI change over time in children and time interaction with maternal migration status (P

Objective. To assess the impact of Mexico City and federal smoke-free legislation on secondhand tobacco smoke (SHS) exposure and support for smoke-free laws. Material and Methods. Pre- and post-law data were analyzed from a cohort of adult smokers who participated in the International Tobacco Control (ITC) Policy Evaluation Suvey in four Mexican cities. For each indicator, we estimated prevalence, changes in prevalence, and between-city differences in rates of change. Results. Self-reported exposure to smoke-free media campaigns generally increased more dramatically in Mexico City. Support for prohibiting smoking in regulated venues increased overall, but at a greater rate in Mexico City than in other cities. In bars and restaurants/cafés, self-reported SHS exposure had significantly greater decreases in Mexico City than in other cities; however, workplace exposure decreased in Tijuana and Guadalajara, but not in Mexico City or Ciudad Juárez. Conclusions. Although federal smoke-free legislation was associated with important changes smoke-free policy impact, the comprehensive smoke-free law in Mexico City was generally accompanied by a greater rate of change.Objetivo. Evaluar el impacto de la legislación federal y del Distrito Federal (DF) de espacios libres de humo de tabaco (ELHT) sobre la exposición al humo de tabaco y el apoyo a las leyes. Material y métodos. Se analizaron datos antes y después de la ley en una cohorte de fumadores adultos de cuatro ciudades mexicanas donde se aplicó la Encuesta Internacional para Evaluar las Políticas Públicas para el Control del Tabaco (Encuesta ITC). Para cada indicador, se estimó la prevalencia, cambios en la prevalencia y diferencias entre ciudades en las tasas de cambio. Resultados. La exposición autorreportada a las campañas sobre los ELHT incrementaron dramáticamente en el DF. El apoyo para prohibir fumar en lugares regulados aumentó en general, pero aumentó más en el DF. La exposición autorreportada al humo de tabaco en bares y restaurantes, en el DF disminuyó significativamente más que en las otras ciudades; sin embargo, la exposición en lugares de trabajo disminuyó en Tijuana y Guadalajara, pero no en el DF o Ciudad Juárez. Conclusiones. La ley federal que promovió ELHT tuvo impactos importantes; sin embargo, la ley del DF, que es más integral, fue acompañada por unas mayores tasas de cambio.