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BACKGROUND AND PURPOSE: High levels of 25-hydroxyvitamin D3 (25[OH]D3 ) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS. METHODS: A nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3 /DBP) × 103 . MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Serum samples from 660 pairs of matched cases and controls were included. At

Aims: To evaluate the long-term effect of the Tät®II app for treatment of urgency (UUI) and mixed urinary incontinence (MUI). Methods: Long-term follow-up of a randomized controlled trial, including 123 women ≥18 years old with UUI or MUI, without red-flag symptoms, and ≥2 leakages per week. All participants, regardless of group, had received the intervention, a treatment app, at the long-term follow-up. Long-term data were collected through web-based questionnaires 15 months after participants received the intervention. The app included pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, an exercise log, reminders, reinforcement messages, and tailored advice. The primary outcome was a change in incontinence symptoms (International Consultation on Incontinence Questionnaire [ICIQ]—Urinary Incontinence Short Form [ICIQ-UI SF]), from baseline to follow-up. Other outcomes were urgency symptoms (ICIQ—Overactive Bladder Module (ICIQ-OAB)), quality of life (ICIQ—Lower Urinary Tract Symptoms Quality of Life Module [ICIQ-LUTSqol]), and improvement (Patient's Global Impression of Improvement [PGI-I]). Results: Of the 123 women, 102 (83%) completed the long-term follow-up. The ICIQ-UI SF mean score improved from 11.5 to 7.6 (mean difference 4.0, 95% CI 3.2–4.7). The ICIQ-OAB improved from 6.7 to 5.5 (mean difference 1.3, 95% CI 0.9–1.6) and the ICIQ-LUTSqol improved from 38.0 to 30.9 (mean difference 7.1, 95% CI 5.7–8.5). Of the 102 women, 74 (73%) reported improvement. Conclusions: Self-management with the Tät®II app for UUI and MUI had a significant effect across all outcome measures also long-term and might serve as an alternative first-line treatment for these conditions.

In late 2010, an outbreak of Cryptosporidium hominis affected 27,000 inhabitants (45%) of Östersund, Sweden. Previous research shows that abdomen and joint symptoms commonly persist up to 5 years post-infection. It is unknown whether Cryptosporidium is associated with sequelae for a longer duration, how persisting symptoms present over time, and whether sequelae are associated with prolonged infection. In this prospective cohort study, a randomly selected cohort in Östersund was surveyed about cryptosporidiosis symptoms in 2011 (response rate 69.2%). A case was defined as a respondent reporting new diarrhoea episodes during the outbreak. Follow-up questionnaires were sent after 5 and 10 years. Logistic regressions were used to examine associations between case status and symptoms reported after 10 years, with results presented as adjusted odds ratios (aOR) with 95% confidence intervals. Consistency of symptoms and associations with case status and number of days with symptoms during outbreak were analysed using X2 and Mann–Whitney U tests. The response rate after 10 years was 74% (n = 538). Case status was associated with reporting symptoms, with aOR of ~3 for abdominal symptoms and ~2 for joint symptoms. Cases were more likely to report consistent symptoms. Cases with consistent abdominal symptoms at follow-up reported 9.2 days with symptoms during the outbreak (SD 8.1), compared to 6.6 days (SD 6.1) for cases reporting varying or no symptoms (p = 0.003). We conclude that cryptosporidiosis was associated with an up to threefold risk for reporting symptoms 10 years post-infection. Consistent symptoms were associated with prolonged infection.

In 2010, 27,000 inhabitants (45% of the population) of Östersund, Sweden, contracted clinical cryptosporidiosis after drinking water contaminated withThis observational study included adult patients (≥18 years old) from the local health care region who were diagnosed with pathology-confirmed IBD or MC during 2006-2019. We collected and validated the diagnosis, date of diagnosis, age at diagnosis, and sex from the Swedish quality register SWIBREG and electronic patient records. Population data were collected from Statistics Sweden. The incidences for 2006-2010 (pre-outbreak) and 2011-2019 (post-outbreak) were evaluated by negative binomial regression analysis and presented as incidence rate ratios (IRRs). Data were analyzed for IBD, for UC and CD separately, and MC.During the study period, we identified 410 patients with new onset IBD and 155 new cases of MC. Overall, we found a trend toward an increased incidence of IBD post-outbreak (IRR 1.39, confidence interval (CI) 0.99-1.94). In individuals ≥40 years old, the post-outbreak incidence significantly increased for IBD (IRR 1.69, CI 1.13-2.51) and CD (IRR 2.23, CI 1.08-4.62). Post-outbreak incidence of MC increased 6-fold in all age groups (IRR 6.43, CI 2.78-14.87).The incidence of late-onset IBD and MC increased after the

High levels of 25-hydroxyvitamin DA nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)DSerum samples from 660 pairs of matched cases and controls were included. At20 years of age, high levels of free vitamin DThese findings support the hypothesis that high levels of free 25(OH)D

Introduction and hypothesis Previous studies have found high prevalence rates of anxiety and depression in women with urinary incontinence (UI). This study investigates the prevalence in women who had turned to eHealth for treatment of UI and identifies possible factors associated with depression. Methods We analyzed data from two randomized controlled trials evaluating eHealth treatment for UI, including 373 women with stress UI (SUI), urgency UI (UUI), or mixed UI (MUI). We used the Hospital Anxiety and Depression Scale (HADS) and defined a score of ≥8 as depression or anxiety. The ICIQ-UI-SF questionnaire was used to score incontinence severity. Logistic regression was used to determine factors associated with depression and anxiety. Results Women with UUI or MUI were older than women with SUI, mean age 58.3 vs 48.6 years (p = Conclusion The odds of depression in women with MUI/UUI were increased compared with SUI. The prevalence of anxiety and depression was considerably lower than reported in large cross-sectional surveys. Socioeconomic differences may partly explain this finding, as the use of eHealth still is more common among highly educated women.

Background C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS). Objectives To assess CRP as a risk factor for MS. Methods Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z-scored CRP values. Results Levels of CRP were not associated with MS risk. Conclusions We found no association between CRP levels and risk of MS development.

To evaluate the usefulness of a mobile app to support pelvic floor muscle training (PFMT) started prior to radical prostatectomy (RP).A prospective cohort study conducted in Sweden from June 2018 to February 2021 including men for whom RP was planned within 12 months. Users responded anonymously to questionnaires at baseline, 1 and 3 months. Our primary aim was to evaluate if the app could facilitate PFMT and increase confidence in performing pelvic floor muscle (PFM) contractions correctly. Our second aim was to describe the change in urinary incontinence (UI) after RP, based on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF).Of the 3043 users at baseline, 388 met the primary inclusion criteria. Of those, 71 (18.3%) were incontinent, predominantly with slight symptoms. The most common type was urge UI, 39/71 (54.9%). Of the 388 users, 159 (41.0%) answered the questionnaire at 1 month, and 131 (33.7%) at 3 months within 89-135 days. Of those 131, 127 (96.9%) indicated that the app facilitated their training 'a lot' or 'somewhat'. Confidence in performing PFM contractions correctly increased from 39.7% at baseline to 74.0% at 1 month and 87.8% at 3 months (The mobile app facilitated pelvic floor muscle training for men who were planned to undergo radical prostatectomy and used the app.

Background and purpose Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, it was sought to increase the understanding of CMV in MS aetiology. Methods A nested case-control study was performed with presymptomatically collected blood samples identified through crosslinkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95% confidence interval (CI) for CMV seropositivity as a risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating the attributable proportion due to interaction (AP). Results Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65). Conclusions Cytomegalovirus seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity. Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [2015-02419, 2018-03918]; Visare Norr Fund, Northern County Councils Regional Federation [940405]; Research and Development Unit, Region Jamtland Harjedalen [JLL-939768]; Margaretha af Ugglas stiftelse; Swedish Neuro Foundation; MS Research fund; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Swedish Brain Foundation; Horizon 2020 MultipleMS Grant [733161]

BACKGROUND Many women experience urgency (UUI) and mixed (MUI) urinary incontinence but commonly hesitate to seek care. Treatment access and self-management for these conditions can be supported through eHealth approaches. OBJECTIVE This study aimed to investigate the efficacy of the mobile app Tät II for self-management of UUI and MUI in women. METHODS This randomized controlled trial included women ≥18 years old with UUI or MUI and ≥2 leakages per week. Those with red-flag symptoms were excluded. Participants were recruited via analog and digital advertisements and screened for initial selection through a web-based questionnaire. Data were collected using another questionnaire and a 2-day bladder diary. A telephone interview confirmed the symptom diagnosis. Participants were randomized (1:1) to receive access to a treatment app (including pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, tailored advice, exercise log, reinforcement messages, and reminders) or an information app (control group), with no external treatment guidance provided. The primary outcome was incontinence symptoms at the 15-week follow-up, measured using the International Consultation on Incontinence Questionnaire (ICIQ)−Urinary Incontinence Short Form (ICIQ-UI SF). Urgency symptoms were assessed using the ICIQ−Overactive Bladder Module (ICIQ-OAB) and quality of life, using the ICIQ−Lower Urinary Tract Symptoms Quality of Life Module (ICIQ-LUTSqol). Incontinence episode frequency (IEF) was calculated per bladder diary entries. Improvement was measured using the Patient’s Global Impression of Improvement. All outcomes were self-reported. Cure was defined as no leakages per the bladder diary. Intention-to-treat analysis was performed. RESULTS Between April 2017 and March 2018, 123 women (mean age 58.3, SD 9.6 years) were randomized to the treatment (n=60, 2 lost to follow-up) or information (n=63) group. Of these, 35 (28%) women had UUI, and 88 (72%) had MUI. Mean ICIQ-UI SF score at follow-up was lower in the treatment group than in the information group (estimated difference −3.1, 95% CI −4.8 to −1.3). The estimated between-group difference was −1.8 (95% CI −2.8 to −0.99) for mean ICIQ-OAB score and −6.3 (95% CI −10.5 to −2.1) for the mean ICIQ-LUTSqol score at follow-up. IEF reduction from baseline to follow-up was greater in the treatment group (−10.5, IQR −17.5 to −3.5) than in the information group (P CONCLUSIONS The treatment app was effective for improving urgency and mixed incontinence in women. When self-management is appropriate, this app may be a good alternative to pharmacological treatment or other conservative management, thus increasing access to care. CLINICALTRIAL ClinicalTrials.gov NCT03097549; https://clinicaltrials.gov/ct2/show/NCT03097549

Objective: Secundum atrial septal defect (ASD II) is a common congenital heart defect, and interatrial communications among preterm children is even more common. The objective of this study was to calculate the incidence of ASD II in children, with assessment to gestational age at birth. Further, to assess maternal, prenatal and postnatal risk factors associated with ASD II among children of different gestational age at birth. Design: This national registry based retrospective incidence study was supplemented with a national case-control study, using the Swedish Register of Congenial Heart Disease, Swedish Medical Birth Register and Statistics Sweden. All children, 0-18 years of age, born in Sweden and diagnosed with an ASD II between 2010 and 2015 were included in the study and compared with children without diagnosis of ASD II. Results: The yearly overall incidence of ASD II was 150 per 100 000 live births. However, this incidence ranged from 449 per 100 000 live births to 1737 per 100 000 live births, with higher incidence among preterm children. ASD II was associated with a presence of persistent ductus arteriosus; OR = 8.11 (Cl 95% 2.80-16.69), female gender; OR = 1.39 (Cl 95% 1.18-1.63) and being small for gestational age; OR = 1.86 (Cl 95% 1.29-2.68). Born preterm was also associated with ASD II; born at 32-36 gestational children; OR = 3.21 (Cl 95% 2.46-4.19), and born

Background The rate of caesarean section without medical indication is rising but the risk for surgical complications has not been fully explored. Methods Altogether 79 052 women from the Swedish Medical Birth Register who delivered by caesarean section only from 2005 through 2016 were identified and compared with a control group of women delivering vaginally only from the same register and the same period of time. By cross-linking data with the National Patient Register the risks for bowel obstruction, incisional hernia and abdominal pain were analysed, as well as risk factors for these complications. We also analysed acute complications, uterine rupture, and placenta praevia. Findings Caesarean section is associated with an increased risk for bowel obstruction (OR 2.92; CI 2.55–3.34), surgery for bowel obstruction (OR 2.12; CI 1.70–2.65), incisional hernia (OR 2.71; CI 2.46–3.00), surgery for incisional hernia (OR 3.35; CI 2.68–4.18), and abdominal pain (OR 1.41; CI 1.38–1.44). Smoking, obesity, and more than one section delivery added significantly to the risk for these complications. Interpretation Caesarean section is considered a safe procedure, but awareness of the risk for serious complications is important when deciding on mode of delivery. In this study, more than one section, obesity and smoking significantly increased the risk for complications after caesarean section. Prevention of smoking and obesity among fertile women worldwide must continue to be a high priority.

Aims/hypothesis We aimed to compare the risks of severe asphyxia-related neonatal complications in the offspring of mothers with type 1 or type 2 diabetes, and to assess the impact of maternal overweight/obesity on these risks. Methods This was a population-based study of 1,343,751 live-born singleton infants in Sweden between 1997 and 2011, including 5941 and 711 infants of mothers with type 1 and type 2 diabetes, respectively. ORs with 95% CIs were calculated for low Apgar score (0–6) at 5 min after birth, hypoxic ischaemic encephalopathy and neonatal seizures. Results The rates of a low Apgar score were 0.9%, 2.6% and 2.1% in the offspring of mothers without diabetes or with type 1 or type 2 diabetes, respectively. After controlling for maternal confounders (including BMI), the risk of a low Apgar score increased in the offspring of mothers with type 1 diabetes (OR 2.67, 95% CI 2.23, 3.20) but not in the offspring of mothers with type 2 diabetes (OR 1.25, 95% CI 0.66, 2.35). The ORs of hypoxic ischaemic encephalopathy or neonatal seizures were increased in the offspring of mothers with type 1 diabetes (OR 3.41, 95% CI 2.58, 4.49) and type 2 diabetes (OR 2.54, 95% CI 1.13, 5.69). Maternal overweight/obesity was a risk factor for asphyxia-related neonatal complications and low Apgar scores in the offspring of mothers with type 1 diabetes and mothers without diabetes. Conclusions/interpretation The risks of a low Apgar score and severe asphyxia-related neonatal complications are increased in the offspring of mothers with type 1 or type 2 diabetes. Maternal overweight/obesity is an important contributing factor.

Background Many women experience urgency (UUI) and mixed (MUI) urinary incontinence but commonly hesitate to seek care. Treatment access and self-management for these conditions can be supported through eHealth approaches. Objective This study aimed to investigate the efficacy of the mobile app Tät II for self-management of UUI and MUI in women. Methods This randomized controlled trial included women ≥18 years old with UUI or MUI and ≥2 leakages per week. Those with red-flag symptoms were excluded. Participants were recruited via analog and digital advertisements and screened for initial selection through a web-based questionnaire. Data were collected using another questionnaire and a 2-day bladder diary. A telephone interview confirmed the symptom diagnosis. Participants were randomized (1:1) to receive access to a treatment app (including pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, tailored advice, exercise log, reinforcement messages, and reminders) or an information app (control group), with no external treatment guidance provided. The primary outcome was incontinence symptoms at the 15-week follow-up, measured using the International Consultation on Incontinence Questionnaire (ICIQ)−Urinary Incontinence Short Form (ICIQ-UI SF). Urgency symptoms were assessed using the ICIQ−Overactive Bladder Module (ICIQ-OAB) and quality of life using the ICIQ−Lower Urinary Tract Symptoms Quality of Life Module (ICIQ-LUTSqol). Incontinence episode frequency (IEF) was calculated per bladder diary entries. Improvement was measured using the Patient’s Global Impression of Improvement. All outcomes were self-reported. Cure was defined as no leakages per the bladder diary. Intention-to-treat analysis was performed. Results Between April 2017 and March 2018, 123 women (mean age 58.3, SD 9.6 years) were randomized to the treatment (n=60, 2 lost to follow-up) or information (n=63) group. Of these, 35 (28%) women had UUI, and 88 (72%) had MUI. Mean ICIQ-UI SF score at follow-up was lower in the treatment group than in the information group (estimated difference −3.1, 95% CI −4.8 to −1.3). The estimated between-group difference was −1.8 (95% CI −2.8 to −0.99) for mean ICIQ-OAB score and −6.3 (95% CI −10.5 to −2.1) for the mean ICIQ-LUTSqol score at follow-up. IEF reduction from baseline to follow-up was greater in the treatment group (−10.5, IQR −17.5 to −3.5) than in the information group (P Conclusions The treatment app was effective for improving urgency and mixed incontinence in women. When self-management is appropriate, this app may be a good alternative to pharmacological treatment or other conservative management, thus increasing access to care. Trial Registration ClinicalTrials.gov NCT03097549; https://clinicaltrials.gov/ct2/show/NCT03097549

ObjectivesThe public health disorder gastro-oesophageal reflux disease (GORD) is linked with several comorbidities, including oesophageal adenocarcinoma (OAC), but whether life expectancy is reduced by GORD is uncertain. This study assessed all-cause and cancer-specific mortality in GORD after controlling for confounding by heredity and other factors.DesignPopulation-based cohort study from 1998 to 2015.SettingSwedish nationwide study.ParticipantsTwins (n=40 961) born in 1958 or earlier in Sweden.ExposureGORD symptoms reported in structured computer-assisted telephone interviews.OutcomesThe primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality among twins with GORD and twins without GORD. HRs and 95% CIs were analysed using parametric survival models, both in individual twin analyses and co-twin pair analyses, with adjustment for body mass index, smoking, education and comorbidity.ResultsAmong 40 961 individual twins, 5812 (14.2%) had GORD at baseline and 8062 (19.7%) died during follow-up of up to 16 years. The risks of all-cause mortality (HR=1.00, 95% CI: 0.94–1.07) and cancer-specific mortality (HR=0.99, 95% CI: 0.89–1.10) were not increased in individual twins with GORD compared with individual twins without GORD. Similarly, there were no differences in mortality outcomes in within-pair analyses. The OAC-specific mortality rate was 0.45 (95% CI: 0.32–0.66) per 1000 person-years in individual twins with GORD and 0.22 (95% CI: 0.18–0.27) per 1000 person-years without GORD, rendering an adjusted HR of 2.01 (95% CI: 1.35–2.98).ConclusionsGORD did not increase all-cause or cancer-specific mortality when taking heredity and other confounders into account. The increased relative risk of mortality in OAC was low in absolute numbers.

About 7000 Swedish citizens were on Christmas holiday in the disaster area at the time of the South-east Asian tsunami in 2004, in many cases with children and adolescents in their families.To investigate how adolescents experience a traumatic exposure to a natural disaster.Twenty adolescents aged 16-19 years, who had experienced the 2004 tsunami and participated in a follow-up study 19 months post-disaster, were randomly selected and interviewed about their reactions, their life afterwards and their families. The study combines the face-to-face, semi-structured interviews with questionnaire data on mental health for 4910 Swedish adolescents and adults.The themes that emerged inductively during the analysis of the interviews were psychological reactions during the catastrophe, the coping after, changes in self-image, worldview, role in the family, risk interpretation and altruism. The disaster had profound impact on family relations, social networks and plans for the future. Many felt strengthened by the experience and by their ability to cope in comparison with other family members, but also perceived isolation and lack of understanding. The general mental health status among the adolescents did not differ significantly from those of older age at the 19-month follow-up.According to the adolescents', they experienced the tsunami-disaster differently than others around them. Their subjective interpretation of the event and its aftermath indicates resilience, especially among the young men. Future follow-up studies in larger samples of both symptoms and psychological functioning are warranted.

In a population-based case-control study, we investigated whether familial confounding influenced the associations between maternal overweight/obesity and risks of stillbirth and infant mortality by including both population and sister controls. Using nationwide data from the Swedish Medical Birth Register (1992-2011), we included all primiparous women with singleton births who also had a sister with a first birth during that time period. We used logistic regression analyses to calculate odds ratios (and 95% confidence intervals) adjusted for maternal age, height, smoking habits, education, and time period (5-year groups) of child's birth. Body mass index (BMI) was calculated as weight (kg)/height (m)(2). Compared with population controls with a normal BMI (18.5-24.9), stillbirth risk increased with increasing BMI (BMI 25-29.9: odds ratio (OR) = 1.51 (95% confidence interval (CI): 1.21, 1.89); BMI 30-34.9: OR = 1.77 (95% CI: 1.24, 2.50); BMI a parts per thousand yen35: OR = 3.16 (95% CI: 2.10, 4.76)). The sister case-control analyses revealed similar results. Offspring of obese women (BMI a parts per thousand yen30) had an increased risk of infant mortality when population controls were used (OR = 2.41, 95% CI: 1.83, 3.16), and an even higher risk was obtained when sister controls were used (OR = 4.04, 95% CI: 2.25, 7.25). We conclude that obesity in early pregnancy is associated with increased risks of stillbirth and infant mortality independently of genetic and early environmental risk factors shared within families.

Study Objectives: To investigate the potentially bidirectional association between gastroesophageal reflux symptoms (GERS) and sleep disturbances/ insomnia disorders. Methods: We assessed the incidence of new-onset of self-reported GERS, sleep disturbances, and insomnia disorders in a population-based longitudinal cohort study (HUNT), performed in Nord-Trøndelag County, Norway. Modified Poisson regression was used to estimate risk ratios (RRs) with 95% confidence intervals (CIs), adjusted for sex, age, body mass index, tobacco smoking, educational level, anxiety, and depression. Results: The study cohort included the 25,844 participants of the HUNT study who responded to health questionnaires in both 1995–1997 and 2006–2009. New-onset GERS, sleep disturbances, and insomnia disorders was reported in 396 (2%), 2,598 (16%), and 497 (3%) participants, respectively. Persistent sleep disturbances were associated with new-onset GERS (RR: 2.70, 95% CI: 1.93–3.76), persistent insomnia disorders were associated with new-onset GERS (RR: 3.42; 95% CI: 1.83–6.39) and persistent GERS was associated with new-onset sleep disturbances (RR: 1.41; 95% CI: 1.14–1.75). Conclusions: Sleep disturbances and GERS seem to be bidirectionally associated, and sleep disturbances seem to be a stronger risk factor for GERS than the reverse. Significance The present study found that sleep disturbances and gastroesophageal reflux symptoms (GERS) are bidirectionally associated, suggesting that sleep disturbances may lead to GERS and vice versa. The study indicates a stronger association between sleep disturbances and risk of GERS than the opposite. The results are supported by the longitudinal design that enabled assessment of new-onset sleep disturbances and GERS and an observed dose-response relation, with increased risk with longer exposure. The study highlights the need for research aiming at preventing or treating both of these disorders. Interventional studies addressing whether treatment of sleep disturbances decreases the risk of developing GERS and whether effective treatment of GERS counteracts sleep disturbances are warranted. This is a pre-copyedited, author-produced version of the article accepted for publication in following peer review. The version of record is available online at: http://dx.doi.org/10.5665/sleep.5976.

The risk of cancer in the gastric remnant after distal gastrectomy for benign ulcer disease has been assessed mainly in studies of small sample size, selected series and limited follow-up time. This was a population-based cohort study of patients who had undergone distal gastrectomy for benign ulcer disease in 1964-2008 in Sweden. Data for follow-up for cancer and censoring for death were obtained from nationwide registries of Cancer and Population, respectively. The number of observed cancer cases in the gastrectomy cohort was divided by the expected number, calculated from the cancer incidence of the Swedish population of corresponding age, sex and calendar year. Relative risks were presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). The distal gastrectomy cohort included 18,912 patients and 323,676 person-years at risk. The observed total number of gastric stump cancers (n = 140) was not higher than expected (SIR 0.84, 95% CI 0.71-0.99). There was no increased SIR with latency periods shorter than 30 years; increase was seen only among patients who had undergone gastric resection over 30 years earlier (SIR 2.29, 95% CI 1.38-3.57). Sex, age, ulcer location and type of surgical reconstruction were not associated with any considerable differences in SIR. In conclusion, this large population-based study revealed an increased risk of cancer in the gastric remnant only 30 years or longer after gastric resection for benign disease, whereas other factors did not influence this risk.

Background: Gastrectomy has been indicated as a risk factor for laryngeal cancer, and possibly also for pharyngeal cancer, but few studies are available. The postulated mechanism is increased bile reflux following gastrectomy. Methods: This was a population-based cohort study of patients who underwent gastrectomy for peptic ulcer disease between 1964 and 2008 in Sweden. Follow-up data for cancer was obtained from the Swedish Cancer Register. Relative risk was calculated as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Results: The gastrectomy cohort comprises 19 767 patients, contributing 348 231 person-years at risk. The observed number of patients with laryngeal (n=56) and pharyngeal cancer (n=28) was two-fold higher than the expected (SIR: 2.0, 95% CI: 1.5–2.6 and SIR: 2.4, 95% CI: 1.6–3.5, respectively). After exclusion of 5536 cohort members with tobacco- or alcohol-related disease, the point SIRs remained increased (SIR: 1.6, 95% CI: 1.1–2.2 and SIR: 1.7, 95% CI: 0.9–2.8, respectively). The SIRs of laryngeal and pharyngeal cancer increased with time after gastrectomy (P for trend

Background The influence of bile reflux in the development of oesophageal adenocarcinoma remains controversial. This was tested in a cohort of patients who had undergone gastrectomy, a procedure often entailed by substantial bile reflux. Methods A population-based cohort study of patients who had undergone gastrectomy for peptic ulcer disease in 1964–2008 in Sweden. Follow-up for cancer and censoring for death were achieved through linkages to nationwide registries of Cancer and Population, respectively. The number of observed cancer cases in the gastrectomy cohort was divided by the expected number, calculated from the incidence of the entire Swedish population of corresponding age, sex and calendar year. Relative risks were thus presented as standardised incidence ratios with 95% confidence intervals. Results After exclusion of all person-years the first year after surgery, the final gastrectomy cohort comprised of 19,767 patients. These patients were followed up for a median of 17 years, and contributed with a total of 348,231 person-years at risk. The observed number of patients with oesophageal adenocarcinoma ( n = 7) was not higher than the expected ( n = 11.6), providing a standardised incidence ratio of 0.6 (95% CI 0.2–1.2). There were no clear differences between sexes, age groups or latency intervals after gastrectomy. Conclusions Gastrectomy for peptic ulcer disease does not appear to increase the risk of oesophageal adenocarcinoma.

The risk of developing enduring post-traumatic stress reactions and mental health problems in the aftermath of disasters is substantial. However, there are inconsistencies regarding the contribution of physical injury as an independent risk factor for developing psychiatric morbidity after disasters.The aim was to assess whether physical injury was associated with post-traumatic stress reactions and general mental health after adjusting for perceived life-threat in the aftermath of the 2004 tsunami.A sample of 1501 highly exposed survivors from the 2004 Southeast Asia tsunami was selected from a cohort of Swedish survivors surveyed 14 and 36 months after the event. The impact of physical injury on post-traumatic stress and general mental health was assessed by regression models accounting for subjective life-threat.Physical injury was associated with higher levels of post-traumatic stress reactions and poorer general mental health. These associations were observed at both 14 and 36 months after the disaster.Physical injury has a specific contribution to the association between traumatic experience and both post-traumatic stress reactions and general mental health in victims of the 2004 tsunami. The effect is stable over several years.

BACKGROUND: There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. AIM: To investigate the risk for ADHD in children conceived after IVF. METHODS: Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel-Haenszel procedures. We studied 28 158 children born after IVF and compared them with 2 417 886 children in the population. RESULTS: After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio=1.18, 95% confidence interval 1.03-1.36. The effect was stronger in girls (OR=1.40) than boys (OR=1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. CONCLUSIONS: The study suggests a weak association between IVF and drug treated ADHD.

BACKGROUND Relatively few studies published to date have investigated IVF and cancer risk. In this study we compared the occurrence of cancer in women who gave birth after IVF with all other women who gave birth in the study period. METHODS All women who were treated with IVF and gave birth during the years 1982-2006 in Sweden were identified from all IVF clinics, and the occurrence of cancer in these women was identified by linkage with the nationwide Swedish cancer register. Comparison was made with Mantel-Haenszel odds ratios (ORs), adjusting for year of delivery and maternal age, parity and smoking. Cancer before IVF was only studied in first parity women. Specific cancer forms were also studied. RESULTS Among 24058 women who had been treated with IVF, 1279 appeared in the cancer register. The total number of women studied in the population was 1 394 061, and 95 775 of these were registered in the cancer register. The risk for cancer before IVF was increased [OR 1.37, 95% confidence interval (CI) 1.27-1.48] and was especially high for ovarian cancer (3.93). The risk for cancer after IVF was significantly lower (OR 0.74, 95% CI 0.67-0.82), mainly due to a lower than expected risk for breast and cervical cancer. The risk for ovarian cancer was increased but lower than the risk before IVF (2.13). CONCLUSIONS Cancer or cancer treatment may increase the risk for infertility leading to IVF. After IVF, in most cases with treatment with fertility hormones, a significantly low cancer risk was found. Ovarian cancer showed an increased risk, although lower than before IVF. One possible reason is ovarian pathology causing both infertility and an increased cancer risk.

Objective: To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF. Design: Register study. Setting: Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006. Patient(s): Treatments reported from all Swedish IVF clinics. Intervention(s): None. Main Outcome Measure(s): Some neonatal characteristics were compared in 1,311 infants born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687). Result(s): After adjusting for year of birth, maternal age, parity, smoking habits, and body mass index, the risk of preterm birth among singletons was significantly greater after blastocyst-stage transfer than after cleavage-stage transfer. The risk of congenital malformations was also significantly higher. When the analysis was restricted to clinics where blastocyst transfers were made, the risk estimates increased for preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but did not change for congenital malformations. Conclusion(s): The results indicate a small increase in risk associated with blastocyst transfer, perhaps owing to the longer period of in vitro culture. There is a possibility that this effect is due, at least in part, to a selection of women for blastocyst transfers. Further studies are needed either to verify or to refute the found associations.

PURPOSE: To follow up children born after in vitro fertilization (IVF) with respect to eye malformations and poor visual acuity. DESIGN: Observational cohort study based on Swedish health registers. METHODS: Congenital eye malformations were studied in 32 091 children born from 1982 through 2007 and severe visual impairment was studied in 24 628 children born from 1985 through 2005 after IVF in Sweden. Comparisons were made with all children born in Sweden during corresponding periods with adjustment for various confounders. The main outcome measure was the presence of a congenital eye malformation and poor visual acuity. RESULTS: Thirty-six (1.1 per 1000) IVF infants with ocular malformations were identified, and the risk, compared with non-IVF children, was not increased when adjusted for maternal age, parity, smoking, and body mass index (odds ratio, 1.05; 95% confidence interval, 0.75 to 1.47). Severe visual impairment was identified in 25 cases (1.0 per 1000), and the risk increase was statistically significant (odds ratio, 1.65; 95% confidence interval, 1.12 to 2.45) and was only slightly reduced when adjustment as above was made (odds ratio, 1.55; 95% confidence interval, 1.04 to 2.32). When adjustment was made for known length of unwanted childlessness, the OR decreased to 1.15 (95% confidence interval, 0.61 to 2.16). Only 3 of the 25 children with visual impairment had ocular malformations. CONCLUSIONS: Although there is an increased risk for visual impairment among children born after IVF, the individual risk is small and may be secondary to parental characteristics. No increased risk for eye malformations was found.

Objective To compare neonatal outcome among twins conceived after in vitro fertilisation (IVF) with that of spontaneously conceived twins. Design Comparison of different-sex (dizygotic) twins born ...

BACKGROUND Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment. METHODS This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred. RESULTS There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little. CONCLUSIONS The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.

Fourteen months after the 2004 tsunami, mental health outcome was assessed in 187 bereaved relatives, 308 bereaved friends, and in 3,020 nonbereaved Swedish survivors. Of the bereaved relatives, 41% reported posttraumatic stress reactions and 62% reported impaired general mental health. Having been caught or chased by the tsunami in combination with bereavement was associated with increased posttraumatic stress reactions. Complicated grief reactions among relatives were almost as frequent as posttraumatic stress reactions. The highest levels of psychological distress were found among those who had lost children. Traumatic bereavement, in combination with exposure to life danger, is probably a risk factor for mental health sequelae after a natural disaster.

Background: Gastroesophageal reflux is overrepresented in people with obstructive sleep apnea (OSA) and it has been suggested that OSA worsens gastroesophageal reflux symptoms. Aggravated reflux might lead to an increased risk of Barrett's esophagus. Aim: To assess the association between sleep apnea symptoms and Barrett's esophagus. Methods: Included in a case-control study in Brisbane, Australia were 237 patients with histologically confirmed Barrett's esophagus and 247 population controls. The controls were randomly selected from the electoral roll and frequency-matched to the cases by age and sex. Information on OSA symptoms (excessive daytime sleepiness and sleep related apnea symptoms), gastroesophageal reflux symptoms and anthropometric measures were collected through interviews and written questionnaires. Multivariable logistic regression provided odds ratios (OR) and 95% confidence intervals (CI), adjusted for potential confounding by BMI and gastroesophageal reflux. Results: The prevalence of Barrett's esophagus was higher among people with excessive daytime sleepiness than those without (24% vs. 18%; p-value 0.1142) and in participants with sleeprelated apnea symptoms (20% vs. 13%; p-value 0.1730). However, there were non-significantly increased ORs of Barrett's esophagus among people with excessive daytime sleepiness (OR 1.42, 95% CI 0.90-2.34) and sleep related apnea symptoms (OR 1.32, 95% CI 0.74-2.36) when adjusting for age, sex and BMI. After further adjustment for gastroesophageal reflux symptoms, the point ORs were no longer increased (OR 1.02, 95% CI 0.61-1.70 for daytime sleepiness and OR 0.72, 95% CI 0.38-1.38 for sleep related apnea symptoms). Conclusions: Symptoms of OSA are possibly associated with an increased risk of Barrett's esophagus, an association that appears to be mediated entirely by gastroesophageal reflux. Copyright

OBJECTIVES: Tobacco smoking increases the risk of gastroesophageal reflux symptoms (GERS), but whether tobacco smoking cessation improves GERS is unclear. The aim of this study was to clarify if tobacco smoking cessation improves GERS. METHODS: The study was based on the Nord-Trøndelag health study (the HUNT study), a prospective population-based cohort study conducted from 1995–1997 to 2006–2009 in Nord-Trøndelag County, Norway. All residents of the county from 20 years of age were invited. The study included 29,610 individuals (61% response rate) who reported whether they had heartburn or acid regurgitation. The association between tobacco smoking cessation and improvement in GERS was assessed by logistic regression, providing odds ratios (ORs) with 95% confidence intervals (CIs). The analyses were stratified by antireflux medication, and the results were adjusted for sex, age, body mass index (BMI), alcohol consumption, education, and physical exercise. Subgroup analyses were also stratified by BMI. RESULTS: Among individuals using antireflux medication at least weekly, cessation of daily tobacco smoking was associated with improvement in GERS from severe to no or minor complaints (adjusted OR 1.78; 95% CI: 1.07–2.97), compared with persistent daily smoking. This association was present among individuals within the normal range of BMI (OR 5.67; 95% CI: 1.36–23.64), but not among overweight individuals. There was no association between tobacco smoking cessation and GERS status among individuals with minor GERS or individuals using antireflux medication less than weekly. CONCLUSIONS: Tobacco smoking cessation was associated with improvement in severe GERS only in individuals of normal BMI using antireflux medication at least weekly, but not in other individual with GERS. © 2014 by the American College of Gastroenterology. This is the authors' accepted and reviewed manuscript of the article.

Sir,Stjernholm et al. report in the January 2010 issue of AOGS on an increase in the rate of cesarean section in Sweden from the early 1990s to 2005 (1). Psychosocial reasons were the dominant indi...

OBJECTIVES:High body mass index (BMI) is an established risk factor of gastroesophageal reflux symptoms (GERS). The aim of this study was to clarify if weight loss reduces GERS.METHODS:The study was part of the Nord-Trondelag health study (the HUNT study), a prospective population-based cohort study conducted in Nord-Trondelag County, Norway. All residents of the county from 20 years of age were invited. In 1995-1997 (HUNT 2) and 2006-2009 (HUNT 3), 58,869 and 44,997 individuals, respectively, responded to a questionnaire on heartburn and acid regurgitation. Among these, 29,610 individuals (61% response rate) participated at both times and were included in the present study. The association between weight loss and reduction of GERS was calculated using logistic regression. The analyses were stratified by antireflux medication and the results adjusted for sex, age, cigarette smoking, alcohol consumption, education, and physical exercise.RESULTS:Weight loss was dose-dependently associated with a reduction of GERS and an increased treatment success with antireflux medication. Among individuals with >3.5 units decrease in BMI, the adjusted odds ratio (OR) of loss of any (minor or severe) GERS was 1.98 (95% confidence interval (CI) 1.45-2.72) when using no or less than weekly antireflux medication, and 3.95 (95% CI 2.03-7.65) when using at least weekly antireflux medication. The corresponding ORs of loss of severe GERS was 0.90 (95% CI 0.32-2.55) and 3.11 (95% CI 1.13-8.58).CONCLUSIONS:Weight loss was dose-dependently associated with both a reduction of GERS and an increased treatment success with antireflux medication in the general population. This is a post-peer-review, pre-copyedit version of an article published in [American Journal of Gastroenterology]. The final authenticated version is available online at: https://www.nature.com/articles/ajg2012466#author-information

Background & Aims Previous studies indicate an association between sleep problems and gastroesophageal reflux disease (GERD). Although both these conditions separately have moderate heritabilities, confounding by genetic factors has not previously been taken into account. This study aimed to reveal the association between sleep problems and GERD, while adjusting for heredity and other potential confounding factors. Methods This cross-sectional population-based study included all 8,014 same-sexed twins of at least 65 years of age and born in Sweden between 1886 and 1958, who participated in telephone interviews in 1998–2002. Three logistic regression models were used 1) external control analysis, 2) within-pair co-twin analysis with dizygotic (DZ) twin pairs discordant for GERD, and 3) within-pair co-twin analysis with monozygotic (MZ) twin pairs discordant for GERD. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and adjusted for established risk factors for GERD, i.e. sex, age, body mass index (BMI), tobacco smoking, and educational level. Results A dose-response association was identified between increasing levels of sleep problems and GERD in the external control analysis. Individuals who often experienced sleep problems had a two-fold increased occurrence of GERD compared to those who seldom had sleep problems (OR 2.0, 95% CI 1.8–2.4). The corresponding association was of similar strength in the co-twin analysis including 356 DZ pairs (OR 2.2, 95% CI 1.6–3.4), and in the co-twin analysis including 210 MZ pairs (OR 1.5, 95% CI 0.9–2.7). Conclusion A dose-dependent association between sleep problems and GERD remains after taking heredity and other known risk factors for GERD into account.

Objective Changes in the occurrence of gastro-oesophageal reflux symptoms (GORS) in the population remain uncertain. This study aimed to determine the prevalence changes, the incidence and the spontaneous loss of GORS. Design This population-based cohort study was conducted within the Nord-Trøndelag Health Study (the HUNT study), a longitudinal series of population-based health surveys in Nord-Trøndelag County, Norway. The study base encompassed all adult residents in the county, and the participants reported the degree of GORS during the previous 12 months. The number of participants included were 58 869 (64% response rate) in 1995–7 and 44 997 (49%) in 2006–9. Of these, 29 610 persons (61%) were prospectively followed up for an average of 11 years. Results Between 1995–7 and 2006–9, the prevalence of any, severe and at least weekly GORS increased by 30% (from 31.4% to 40.9%), 24% (from 5.4% to 6.7%) and 47% (from 11.6% to 17.1%), respectively. The average annual incidence of any and severe GORS was 3.07% and 0.23%, respectively. In women, but not men, the incidence of GORS increased with increasing age. The average annual spontaneous loss (not due to antireflux medication) of any and severe GORS was 2.32% and 1.22%, respectively. The spontaneous loss of GORS decreased with increasing age. Conclusion Between 1995–7 and 2006–9 the prevalence of GORS increased substantially. At least weekly GORS increased by 47%. The average annual incidence of severe GORS was 0.23%, and the corresponding spontaneous loss was 1.22%. The incidence and spontaneous loss of GORS were influenced by sex and age. Copyright information: Published by the BMJ Publishing Group Limited. This is the authors' accepted and reviewed manuscript of the article.