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Objective Antipsychotics may increase serum prolactin, which has particularly been observed with risperidone. Further, hyperprolactinemia has been linked to osteoporosis-related fractures. Therefore, we investigated fracture risk in a nationwide cohort exposed to antipsychotics. Methods Swedish registers were used to identify adults with two consecutive dispensations of risperidone (n = 38 211), other atypical antipsychotics not including paliperidone (n = 60 691), or typical antipsychotics (n = 17 445) within three months between 2006 and 2013. An osteoporosis-related fracture was defined as a non-open hip/femur fracture in primary analyses. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Risperidone users were on average older (mean age of 68, 44, and 63 years for risperidone, other atypical antipsychotics, and typical antipsychotics respectively). Compared with other atypical antipsychotics, there was no association between risperidone and osteoporosis-related fractures in the overall (HR = 1.04, CI: 0.91-1.19) or age-stratified analyses. A significantly increased risk of typical antipsychotics (HR = 1.24, CI: 1.07-1.45) compared with other atypical antipsychotics remained for ages >45 years. Conclusion Risperidone does not appear to be associated with an increased risk of osteoporosis-related fracture compared with other atypical antipsychotic agents as a group. For typical antipsychotics, a moderately elevated risk of hip fractures was noted compared with other atypical antipsychotics, possibly because of residual confounding.

Diets enriched in sucrose severely impair metabolic regulation and are associated with obesity, insulin resistance and glucose intolerance. In the current study, we investigated the effect of 4 weeks high-sucrose diet (HSD) feeding in C57BL6/J mice, with specific focus on adipocyte function. Mice fed HSD had slightly increased adipose tissue mass but displayed similar hepatic triglycerides, glucose and insulin levels, and glucose clearance capacity as chow-fed mice. Interestingly, we found adipose depot-specific differences, where both the non- and insulin-stimulated glucose transports were markedly impaired in primary adipocytes isolated from the inguinal fat depot from HSD-fed mice. This was accompanied by decreased protein levels of both GLUT4 and AS160. A similar but much less pronounced trend was observed in the retroperitoneal depot. In contrast, both GLUT4 expression and insulin-stimulated glucose uptake were preserved in adipocytes isolated from epididymal adipose tissue with HSD. Further, we found a slight shift in cell size distribution towards larger cells with HSD and a significant decrease of ACC and PGC-1α expression in the inguinal adipose tissue depot. Moreover, fructose alone was sufficient to decrease GLUT4 expression in cultured, mature adipocytes. Altogether, we demonstrate that short-term HSD feeding has deleterious impact on insulin response and glucose transport in the inguinal adipose tissue depot, specifically. These changes occur before the onset of systemic glucose dysmetabolism and therefore could provide a mechanistic link to overall impaired energy metabolism reported after prolonged HSD feeding, alone or in combination with HFD.

Background: Surgical audit, sometimes including public reporting, is an important foundation of high quality health care. We aimed to assess the validity of a novel outcome metric, days at home up to 30 days after surgery, as a surgical outcome measure in clinical trials and quality assurance. Methods: This was a multicentre, registry-based cohort study. We used prospectively collected hospital and national healthcare registry data obtained from patients aged 18 years or older undergoing a broad range of surgeries in Sweden over a 10-year period. The association between days at home up to 30 days after surgery and patient (older age, poorer physical status, comorbidity) and surgical (elective or non-elective, complexity, duration) risk factors, process of care outcomes (re-admissions, discharge destination), clinical outcomes (major complications, 30-day mortality) and death up to 1 year after surgery were measured. Findings: From January, 2005, to December, 2014, we obtained demographic and perioperative data on 636,885 patients from 21 Swedish hospitals. Mortality at 30 days and one year was 1.8% and 7.3%, respectively. The median (IQR) days at home up to 30 days after surgery was 27 (23–29), being significantly lower among high-risk patients, those recovering from more complex surgical procedures, and suffering serious postoperative complications (all p

This Swedish nationwide cohort study aims to examine the role of maternal characteristics (maternal age, education, smoking, BMI, diabetes, and preeclampsia) and multiple intrauterine growth measures on the risk of childhood lymphomas. A total of 3 444 136 singleton live births registered in the Swedish Medical Birth Register were analyzed, among whom there were 515 incident non-Hodgkin lymphoma (NHL) cases and 169 Hodgkin lymphoma (HL) cases aged 0-14 years at diagnosis (1973-2007) identified through linkage with the Swedish Cancer Register. Proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) of NHL and HL. Male sex (HR=2.00, 95% CI: 1.66-2.41), older maternal age (HR=1.03, 95% CI: 1.00-1.06, per 1-year increase), and large for gestational age compared with appropriate for gestational age (AGA) birth weight (HR=1.83, 95% CI: 1.20-2.79) were correlated with the risk of NHL; of note, in subanalysis by sex, the latter association was confined to girls (HR=3.37, 95% CI: 1.90-5.97, Pinteraction by sex=0.008). The risk of childhood HL overall was more evident among boys (HR=2.03, 95% CI: 1.46-2.81), whereas indices of accelerated fetal growth were not convincingly associated with the risk of HL. Apart from the established association with sex, the findings point to accelerated intrauterine growth as a risk factor for childhood NHL that may differ by sex. Given the rarity of this condition at birth, however, further studies with more elaborate indices are needed to conclude on its association with rare diseases such as HL.

Background We investigated whether bereavement of a close family member – a source of severe psychological stress exposure – the year before pregnancy is associated with gestational diabetes mellitus (GDM). Methods We studied pregnant women with livebirths in Denmark during 1994–2008 and with births in Sweden during 1987–2006 (n = 2 569 446). We obtained data on death of women's parents, siblings, and older children, and on demographic and health- and pregnancy-related factors through linkage between nationwide registers. Results In multivariable models, death of a close relative the year before pregnancy was associated with a 14% increased odds of GDM [95% confidence intervals (CIs) 1.03, 1.26]. The odds ratios corresponding to the loss of a child, parent, and sibling were 1.51 (95% CI: 1.17, 1.95), 1.12 (95% CI: 1.00, 1.25), and 0.68 (95% CI: 0.40, 1.25), respectively. Deaths due to cardiovascular diseases or diabetes were more closely related to the risk of GDM than other types of deaths. We found no association between unnatural deaths and the risk of GDM. Conclusions Death of a close relative the year before pregnancy was associated with a modestly increased GDM risk. Our findings according to the relative's cause of death suggest that differences in screening for GDM among exposure groups and residual confounding by familial factors related to metabolic and cardiovascular diseases may have contributed to this association. If there is a causal stress effect on GDM in this predominantly Nordic population, it is most likely small.

Aim To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent pneumococcal conjugated vaccine (PCV13), Prevenar13®, compared to a 23-valent pneumococcal polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response. Background Streptococcus pneumoniae causes substantial morbidity in patients with CLL, a group known to respond poorly to polysaccharide vaccines. Comparative studies with conjugated vaccines are lacking. Methods 128 treatment naive CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n = 63) or PPSV23 (n = 65) after stratification by IgG level and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, and at one and six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA). Results PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. PPSV23 did not trigger a better immune response than PCV13 for any of the serotypes, regardless of analysis method or time point of analysis. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated. Conclusions In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for most serotypes common for the two vaccines. We therefore propose that PCV13 should be included in vaccination programs against Streptococcus pneumoniae for CLL patients and administered as early as possible during the course of the disease.

Solid tumors are associated with an increased risk of suicide, however, there is limited detailed information on the risk of suicide in patients with hematological malignancies. Therefore, we conducted a population-based study including 47,220 patients with hematological malignancies (diagnosed 1992–2006) and their 235,868 matched controls to define the incidence and risk factors for suicide and suicide attempt. Information on suicides, suicide attempts, and preexisting psychiatric disorders was obtained from Swedish registers and individual medical records. There was a twofold increased (hazard ratio [HR] = 1.9, 95% confidence interval 1.5–2.3, P

To inform clinical management of glioblastoma patients, we estimated the relative prevalence (present at glioblastoma diagnosis) and incidence (newly diagnosed) of comorbid conditions among these patients and their matched controls. We identified 2,424 glioblastoma patients registered in the Swedish National Cancer Registry between 1993 and 2006. Next, 12,120 randomly sampled population-based controls were individually matched to cases on age, sex and calendar year of diagnosis. We then evaluated patient discharge data for selected potential comorbid conditions. Seizures (odds ratio (OR) 31.6, 95 % confidence interval (CI) 24.7–40.3) and cerebral edema (OR 25.0, 95 % CI 5.5–114) were the most prevalent conditions at diagnosis. Beginning 30 days after diagnosis, increased risks of incident deep vein thrombosis (hazard ratio (HR) 119.7, 95 % CI 60.8–211.0) and pulmonary embolism (HR 92.4, 95 % CI 48.3–176.6) were observed. Risks of incident cardiovascular diseases including heart failure (HR 4.0, 95 % CI 2.6–6.1), coronary artery disease (HR 2.3, 95 % CI 1.7–3.2), and myocardial infarction (HR 1.9, 95 % CI 1.1–3.4) were also elevated among glioblastoma patients. In this first population-based study of both prevalent and incident comorbid conditions among glioblastoma patients, we have quantified risk of those conditions related to the tumor and its treatment—based on nationwide registry data. However, for incident conditions we cannot distinguish between the effects of the tumor and the effects of treatment. A novel finding was the elevated risk of cardiovascular disease among glioblastoma patients; glioblastoma patients should be monitored for signs of cardiovascular disease.

Small studies and anecdotal evidence suggest marked differences in the use of opioids after surgery internationally; however, this has not been evaluated systematically across populations receiving similar procedures in different countries.To determine whether there are differences in the frequency, amount, and type of opioids dispensed after surgery among the United States, Canada, and Sweden.This cohort study included patients without previous opioid prescriptions aged 16 to 64 years who underwent 4 low-risk surgical procedures (ie, laparoscopic cholecystectomy, laparoscopic appendectomy, arthroscopic knee meniscectomy, and breast excision) between January 2013 and December 2015 in the United States, between July 2013 and March 2016 in Canada, and between January 2013 and December 2014 in Sweden. Data analysis was conducted in all 3 countries from July 2018 to October 2018.The main outcome was postoperative opioid prescriptions filled within 7 days after discharge; the percentage of patients who filled a prescription, the total morphine milligram equivalent (MME) dose, and type of opioid dispensed were compared.The study sample consisted of 129 379 patients in the United States, 84 653 in Canada, and 9802 in Sweden. Overall, 52 427 patients (40.5%) in the United States were men, with a mean (SD) age of 45.1 (12.7) years; in Canada, 25 074 patients (29.6%) were men, with a mean (SD) age of 43.5 (13.0) years; and in Sweden, 3314 (33.8%) were men, with a mean (SD) age of 42.5 (13.0). The proportion of patients in Sweden who filled an opioid prescription within the first 7 days after discharge for any procedure was lower than patients treated in the United States and Canada (Sweden, 1086 [11.1%]; United States, 98 594 [76.2%]; Canada, 66 544 [78.6%]; P .001). For patients who filled a prescription, the mean (SD) MME dispensed within 7 days of discharge was highest in United States (247 [145] MME vs 169 [93] MME in Canada and 197 [191] MME in Sweden). Codeine and tramadol were more commonly dispensed in Canada (codeine, 26 136 patients [39.3%]; tramadol, 12 285 patients [18.5%]) and Sweden (codeine, 170 patients [15.7%]; tramadol, 315 patients [29.0%]) than in the United States (codeine, 3210 patients [3.3%]; tramadol, 3425 patients [3.5%]).The findings indicate that the United States and Canada have a 7-fold higher rate of opioid prescriptions filled in the immediate postoperative period compared with Sweden. Of the 3 countries examined, the mean dose of opioids for most surgical procedures was highest in the United States.

Mange studier peger på, at stress hos den gravide kan påvirke udfaldet af graviditeten. Dette studie undersøger, om sorg hos den gravide øger risikoen for dødfødsel. Studiet er baseret på en landsdækkende svensk undersøgelse, som inkluderer data fra knap 3 millioner fødsler i perioden 1973-2006. Demografiske, helbredsmæssige og graviditetsrelaterede oplysninger såvel som information om dødsfald i den gravides nærmeste familie blev trukket fra landsdækkende registre og koblet via cpr-numre. I alt 11.071 dødfødsler (svarende til 3,8 dødfødsler for 1000 fødsler) blev registreret i kohorten. Resultaterne viser, at der var en 18 % øget risiko for dødfødsel hos børn af mødre, som havde mistet et nærtstående familiemedlem i året op til eller under graviditeten, i sammenligning med børn af mødre, som ikke havde været udsat for tab under graviditeten. Dødstidspunktet synes ikke at påvirke sammenhængen mellem tab hos moderen og dødfødsel. Der synes heller ikke at være forskel på, om dødsfaldet var ventet eller uventet. Tab af et nært familiemedlem er en af de alvorligste kilder til stress, og fremtidige studier bør undersøge, om mindre alvorlige og mere udbredte typer af stress også kan medvirke til at øge risikoen for dødfødsel. The role of stress in the pathogenesis of preeclampsia has only been investigated in a few studies, and the findings are not conclusive. We analyzed whether maternal bereavement shortly before or during pregnancy is associated with an increased risk of preeclampsia. We conducted a cohort study of singleton births in Denmark during 1978-2008 and in Sweden during 1973-2006 (n=4 122 490) by linking national population-based registers. Mothers were considered exposed to bereavement if they lost a parent, a sibling, a partner, or a child the year before or during pregnancy (n=124 553). The risk of preeclampsia was slightly increased for women who lost a close relative during the 6 months before conception (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06-1.23) or during the first trimester of pregnancy (OR, 1.15; 95% CI, 1.03-1.29). Exposure during these periods tended to be more closely related to early preeclampsia (delivery before 34 weeks of gestation; OR, 1.37; 95% CI, 1.12-1.67) than to late preeclampsia (OR, 1.13; 95% CI, 1.06-1.20). The strongest association was observed between loss of a child and early preeclampsia when the exposure window was from 6 months before pregnancy until start of second trimester (OR, 4.03; 95% CI, 2.46-6.61). Our results related to timing of exposure suggest that severe stress may influence early placentation. However, the public health implications of our findings are limited in populations with a low prevalence of severe stress exposures.

Increasing evidence suggests that maternal stress during pregnancy may influence pregnancy outcomes. In a nationwide Swedish study including almost 3 million births taking place during 1973-2006, we investigated whether maternal bereavement during pregnancy is associated with stillbirth risk. Through individual record linkage between several population-based registers, we obtained information on demographic, health-related, and pregnancy-related factors and deaths of mothers' first-degree relatives. There were 11,071 stillbirths (3.8 per 1,000 births) in the cohort. After adjustment for potential confounders, infants of mothers who had lost any first-degree relative the year before or during pregnancy had an 18% higher risk of stillbirth than unexposed offspring (95% confidence interval (CI): 1.06, 1.31). Corresponding hazard ratios were 1.67 (95% CI: 1.18, 2.36) for maternal loss of an older child, 2.06 (95% CI: 1.44, 2.94) for loss of a sibling, and 1.07 (95% CI: 0.95, 1.21) for loss of a parent. The relationship between maternal bereavement and stillbirth did not vary by time of death or by whether the relative's death was expected or unexpected. Death of a close relative is one of the most severe sources of stress, and future studies need to investigate whether less severe but more common stressors also increase stillbirth risk.

BACKGROUND: Patients treated for hematological malignancies have an increased risk of serious infections. Diagnosis and prompt initiation of therapy are essential. Bronchoalveolar lavage (BAL) is a well-established investigation for identifying the cause of pulmonary infiltrates in immunocompromised patients. The aim of the study was to determine the diagnostic yield of BAL in patients treated for hematological malignancies and how often it contributed to a modification of the anti-infectious therapy. METHODS: We reviewed records from 151 consecutive BAL procedures in 133 adult patients with hematological malignancies, treated at a tertiary hematology unit from 2004 to 2013. Extensive microbiological work-ups on BAL samples had been performed according to a standardized protocol. RESULTS: A microbiological finding causing the infectious episode could be identified in 59 (39%) cases. In 44 (29%) of the cases, results from BAL had an impact on clinical management either by contributing to a specific diagnosis (25%) or by leading to cessation of ongoing microbiological therapy. The most common diagnoses were invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). Diagnoses of IPA and PJP were based on results from BAL in 65% and 93% of cases, respectively. Several microbiological tests on BAL samples rendered no positive results. Complications were few and mainly mild. CONCLUSION: BAL is still important for either verifying or excluding some of the most important respiratory tract pathogens in patients with hematological malignancies, particularly IPA and PJP. Standardized procedures for BAL sampling should be continually revised to exclude unnecessary microbiological tests.

OBJECTIVES: Thrombocytopenia is an independent adverse prognostic factor in patients with Myelodysplastic syndromes (MDS). Azacitidine, first-line treatment for the majority of patients with higher-risk MDS, is associated with aggravated thrombocytopenia during the first cycles. Eltrombopag is a novel thrombopoietin receptor agonist, which also has been shown to inhibit proliferation of leukaemia cell lines in vitro. This phase I clinical trial was designed to explore the safety and tolerability of combining eltrombopag with azacitidine in patients with MDS. In addition, we assessed the potential effects of eltrombopag on hematopoietic stem and progenitor cells (HSPCs) from included patients. PATIENTS AND METHODS: Previously untreated patients with MDS eligible for treatment with azacitidine and with a platelet count

Knowledge on effective strategies to encourage participation in epidemiological web-based research is scant. We studied the effects of reminders on overall participation. 3,876 employees were e-mailed a baseline web-based lifestyle questionnaire. Nine months later, a follow-up questionnaire was sent. To encourage study participation, 4-5 and 11 e-mail reminders were sent at baseline and follow-up, respectively. Additional reminders (media articles, flyers, SMS etc) were also administered. Reminders (e-mails + additional) were given in low (a parts per thousand currency sign6 reminders), medium (7-9 reminders) or high amounts (> 9 reminders). Participation was examined with respect to participant characteristics (i.e. age, sex, Body Mass Index, occupation), type/number of reminders, and time of participation. Most participants were males, 35-49 years, and field workers (non-office based). About 29 % responded before any e-mail reminder, following 26 and 45 % after 1 respective a parts per thousand yen 2 e-mail reminders. Participant characteristics were not related to when the participants responded. The 4-5 e-mail reminders increased total response rate by 15 %, the eleven by 21 % (greatest increases in September). Those receiving medium amounts of reminders (reference) had the highest response rate (75 %), likewise office workers (54 %) compared to field workers (33 %). High amounts of reminders were particularly effective on office workers. The participants' characteristics were not related to when they responded in this web-based study. Frequent reminders were effective on response rates, especially for those with high Internet availability. The highest increases in response rates were found in September.

Background: While treatment for breast cancer has been refined and overall survival has improved, there is concern that the incidence of brain metastases has increased. Methods: We identified patients in Sweden with incident breast cancer 1998–2006 in the National Cancer Register, and matched these to the National Patient Register to obtain information on hospital admissions for distant metastases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed with Cox regression as estimates of relative risk. Results: Among 50 528 breast cancer patients, 696 (1.4%) were admitted with brain metastases during median 3.5 years of follow-up. Admissions for other metastases were found in 3470 (6.9%) patients. Compared with the period 1998–2000, patients diagnosed with breast cancer 2004–2006 were at a 44% increased risk of being admitted with brain metastases (HR 1.44, 95% CI 1.13–1.85). Conclusion: The incidence of admissions with brain metastases in breast cancer patients was increasing in the mid-2000s in Sweden. These findings support a true increase in incidence of brain metastases among breast cancer patients.

Aliment Pharmacol Ther 2011; 34: 675–681 Summary Background Colon cancer and diverticular disease are most common in the Western world and their incidences tend to increase with advancing age. The association between the diseases remains unclear. Aim To analyse the risk of colon cancer after hospitalisation for diverticular disease. Methods Nationwide case–control study. A total of 41 037 patients with colon cancer during 1992–2006, identified from the Swedish Cancer Register were included. Each case was matched with two control subjects. From the Swedish Inpatient Register, cases and control subjects hospitalised for diverticular disease were identified. Odds ratios (OR) and confidence intervals for receiving a diagnosis of colon cancer after hospital discharge for diverticular disease were calculated. Colon cancer mortality was compared between patients with or without diverticular disease. Results Within 6 months after an admission due to diverticular disease, OR of having a colon cancer diagnosis were up to 31.49 (19.00–52.21). After 12 months, there was no increased risk. The number of discharges for diverticular disease did not affect the risk. Colon cancer mortality did not differ between patients with and without diverticular disease. Conclusions Diverticular disease does not increase the risk of colon cancer in the long term, and a history of diverticular disease does not affect colon cancer mortality. The increased risk of colon cancer within the first 12 months after diagnosing diverticular disease is most likely due to surveillance and misclassification. Examination of the colon should be recommended after a primary episode of symptomatic diverticular disease.

Purpose To compare birth outcomes between women exposed and unexposed to the antiviral medications oseltamivir or zanamivir during pregnancy. Methods This was an observational cohort study including women who gave birth to singletons in Sweden 2005–2007 and their infants. We obtained information from the national health registers and evaluated risks of low Apgar score, small for gestational age (SGA), low birth weight, preterm delivery, congenital malformations, birth-related death (stillbirth and neonatal death combined), and neonatal morbidity by conditional logistic regression. The unexposed [n = 860] were matched to the exposed [n = 86] by birth year and fetal gender. Results A total of 81 women filled a prescription with oseltamivir only, 2 with zanamivir, and 3 with both oseltamivir and zanamivir. Compared with the unexposed infants, the exposed ones had higher risks of late transient hypoglycemia (crude OR = 4.00, 95%CI: 1.26–12.76). There were no statistical increased risks of low Apgar score, congenital malformations, SGA, low birth weight, preterm birth, or birth-related death. Adjusting for maternal age, parity, smoking, and body mass index had minor effects on the results. None of the women exposed to oseltamivir or zanamivir had been admitted to hospital for influenza during their pregnancy. Conclusions Except for an increased risk of late transient hypoglycemia, we found no increased risks of adverse birth outcomes among infants exposed to neuraminidase inhibitors in fetal life compared with the unexposed. Copyright © 2011 John Wiley & Sons, Ltd.

Unscheduled visits to an emergency department (ED) or to primary care (PC) are often followed by further healthcare contacts. Present knowledge about predisposing factors and differences between healthcare levels is sparse. The objectives of this study were to describe and to analyze factors influencing subsequent healthcare contacts within 30 days following a non-urgent ED visit or an unscheduled visit in PC. In this prospective cohort study, subjects were identified and interviewed at the time of a non-urgent ED visit or unscheduled visits to PC. Data of all healthcare contacts during 1 month were collected. The probability of reattendance was analyzed regarding socio-demographic factors, previous and present health care utilization, the physicians' perceptions of the urgency of the visit, and appropriateness of its level of care. More than half of the patients in both settings had at least one contact with healthcare the following month. In 16% of the ED patients and 9% of PC patients, these contacts were to an ED. In the multivariate analysis, patients with regular monitoring of chronic disease were associated with an increased probability of having one or more physician visit the following month (OR 1.97 CI 95% 1.15-3.36). In conclusion, previous health care utilization was associated with an increased probability of one or more further physician visits the following month, regardless of the setting for the index visit or other patients characteristics. Physicians' perception of urgency did not influence the probability of further contacts.

The effects of systemic administration of alpha 2-adrenoceptor agonists on migrating myoelectric complexes and castor oil-induced diarrhoea of the small intestine were studied in conscious rats. Castor oil (1 mg/kg, intraduodenally) disrupted the migrating myoelectric complexes and induced irregular spiking activity with sporadic bursts of myoelectric activity. This change of motility pattern was present concomitant with diarrhoea 1-2 h after instillation of castor oil and during the whole period of diarrhoea. Pre-treatment with clonidine (5-10 micrograms/kg i.v.) or oxymetazoline (5.6-11.2 micrograms/kg i.v.), a peripherally active alpha 2-agonist, inhibited the irregular spiking induced by castor oil and no diarrhoea occurred during the experimental period of 6 h. Thus, the antidiarrhoeal action of peripherally acting alpha 2-adrenoceptor agonists such as oxymetazoline, may be of clinical value in the treatment of diarrhoea.

We investigated whether bereavement of a close family member - a source of severe psychological stress exposure - the year before pregnancy is associated with gestational diabetes mellitus (GDM).We studied pregnant women with livebirths in Denmark during 1994-2008 and with births in Sweden during 1987-2006 (n = 2,569,446). We obtained data on death of women's parents, siblings, and older children, and on demographic and health- and pregnancy-related factors through linkage between nationwide registers.In multivariable models, death of a close relative the year before pregnancy was associated with a 14% increased odds of GDM [95% confidence intervals (CIs) 1.03, 1.26]. The odds ratios corresponding to the loss of a child, parent, and sibling were 1.51 (95% CI: 1.17, 1.95), 1.12 (95% CI: 1.00, 1.25), and 0.68 (95% CI: 0.40, 1.25), respectively. Deaths due to cardiovascular diseases or diabetes were more closely related to the risk of GDM than other types of deaths. We found no association between unnatural deaths and the risk of GDM.Death of a close relative the year before pregnancy was associated with a modestly increased GDM risk. Our findings according to the relative's cause of death suggest that differences in screening for GDM among exposure groups and residual confounding by familial factors related to metabolic and cardiovascular diseases may have contributed to this association. If there is a causal stress effect on GDM in this predominantly Nordic population, it is most likely small.

Objective: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. Material and methods: A nation-wide population-based case–control study was performed, including 13,127 cases hospitalised during 2006–2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as “current” or “former” if a statin prescription was last dispensed ≤125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. Results: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17–1.30]; fully adjusted OR 1.00 [0.94–1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73–1.08]; fully adjusted OR 0.70 [0.55–0.89]). Conclusions: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.

Objective To evaluate the possible effects of exposure to neuraminidase inhibitors during embryo-fetal life with respect to adverse neonatal outcomes and congenital malformations. Design Population based multinational observational cohort study and meta-analysis. Setting National registers covering information on maternal healthcare, births, and prescriptions in Denmark, Norway, and Sweden and the EFEMERIS database from the Haute-Garonne district in France. Participants All women together with their singleton infants born between 1 January 2008 and 31 December 2010. Only infants born at 154 days of gestation or later were included. Infants were defined as exposed if the women filled a prescription during pregnancy for either of the two neuraminidase inhibitors oseltamivir or zanamivir. Main outcomes Low birth weight, low Apgar score, preterm birth, small for gestational age birth, stillbirth, neonatal mortality, neonatal morbidity, and congenital malformations. Crude and adjusted hazard ratios of preterm birth were estimated using Cox regression models. Crude and adjusted odds ratios for other outcomes were estimated by logistic regression models. Results The study included 5824 (0.8%) exposed women and their infants and 692 232 who were not exposed. Exposure to neuraminidase inhibitors in utero was not associated with increased risks of any of the investigated neonatal outcomes, including low birth weight (adjusted odds ratio 0.77, 95% confidence interval 0.65 to 0.91), low Apgar score (adjusted odds ratio 0.87, 0.67 to 1.14), preterm birth (adjusted hazard ratio 0.97, 0.86 to 1.10), small for gestational age birth (adjusted odds ratio 0.72, 0.59 to 0.87), stillbirth (adjusted odds ratio 0.81, 0.51 to 1.30), neonatal mortality (adjusted odds ratio 1.13, 0.56 to 2.28), and neonatal morbidity (adjusted odds ratio 0.92, 0.86 to 1.00). No increased risk of congenital malformations overall associated with maternal exposure was observed during the first trimester (adjusted odds ratio 1.06, 0.77 to 1.48). Similarly, no significantly increased risks of any of the outcomes were observed in an analysis restricted to oseltamivir alone. Conclusions This large multinational register study found no increased risks of adverse neonatal outcomes or congenital malformations associated with exposure to neuraminidase inhibitors during embryo-fetal life. The results support previously reported findings that the use of neuraminidase inhibitors is not associated with increased risks of adverse fetal or neonatal outcomes.

Objective: To evaluate the possible effects of exposure to neuraminidase inhibitors during embryo-fetal life with respect to adverse neonatal outcomes and congenital malformations. Design: Population based multinational observational cohort study and meta-analysis. Setting: National registers covering information on maternal healthcare, births, and prescriptions in Denmark, Norway, and Sweden and the EFEMERIS database from the Haute-Garonne district in France. Participants: All women together with their singleton infants born between 1 January 2008 and 31 December 2010. Only infants born at 154 days of gestation or later were included. Infants were defined as exposed if the women filled a prescription during pregnancy for either of the two neuraminidase inhibitors oseltamivir or zanamivir. Main outcomes: Low birth weight, low Apgar score, preterm birth, small for gestational age birth, stillbirth, neonatal mortality, neonatal morbidity, and congenital malformations. Crude and adjusted hazard ratios of preterm birth were estimated using Cox regression models. Crude and adjusted odds ratios for other outcomes were estimated by logistic regression models. Results: The study included 5824 (0.8%) exposed women and their infants and 692 232 who were not exposed. Exposure to neuraminidase inhibitors in utero was not associated with increased risks of any of the investigated neonatal outcomes, including low birth weight (adjusted odds ratio 0.77, 95% confidence interval 0.65 to 0.91), low Apgar score (adjusted odds ratio 0.87, 0.67 to 1.14), preterm birth (adjusted hazard ratio 0.97, 0.86 to 1.10), small for gestational age birth (adjusted odds ratio 0.72, 0.59 to 0.87), stillbirth (adjusted odds ratio 0.81, 0.51 to 1.30), neonatal mortality (adjusted odds ratio 1.13, 0.56 to 2.28), and neonatal morbidity (adjusted odds ratio 0.92, 0.86 to 1.00). No increased risk of congenital malformations overall associated with maternal exposure was observed during the first trimester (adjusted odds ratio 1.06, 0.77 to 1.48). Similarly, no significantly increased risks of any of the outcomes were observed in an analysis restricted to oseltamivir alone. Conclusions: This large multinational register study found no increased risks of adverse neonatal outcomes or congenital malformations associated with exposure to neuraminidase inhibitors during embryo-fetal life. The results support previously reported findings that the use of neuraminidase inhibitors is not associated with increased risks of adverse fetal or neonatal outcomes. publishedVersion

Background Healthcare information provided by telephone service and internet sources is growing but has not been shown to reduce inappropriate emergency department (ED) visits. Objective To describe the use of advice or healthcare information among patients with non-urgent illnesses seeking care before attendance at an ED, or primary care (PC) centres in an urban region in Sweden. Design Patients with non-urgent illnesses seeking care at an ED or patients attending the PC were followed up with a combination of patient interviews, a questionnaire to the treating physician and a prospective follow-up of healthcare use through a population-based registry. Results Half of the non-urgent patients attending the ED had used healthcare information or advice before the visit, mainly from a healthcare professional source. In PC, men were more likely to have used information or advice compared with women (OR 2.5 95% CI 1.3 to 5.0), whereas the situation was reversed among ED patients (OR=0.4 95% CI 0.2 to 0.9). Men with no previous healthcare experience attending the ED had the lowest use of healthcare information (p Conclusion ED patients rated as non-urgent by the triage nurse used more advice and healthcare information than PC patients, irrespective of the physician-rated urgency of the symptoms. The problem seems not to be lack of information about appropriate ED use, but to find ways to direct the information to the right target group.

We estimated the accuracy of a non-invasive, inexpensive method (the Chinese lunar calendar, CLC) to predict the sex of a baby from around the time of conception, using 2,840,755 singleton births occurring in Sweden between 1973 and 2006. Maternal lunar age and month of conception were estimated, and used to predict each baby's sex, according to a published algorithm. Kappa statistics were estimated for the actual vs. the CLC-predicted sex of the baby. Overall kappa was 0.0002 [95% CI -0.0009, 0.0014]. Accuracy was not modified by year of conception, maternal age, level of education, body mass index or parity. In a validation subset of 1000 births in which we used a website-customised algorithm to estimate lunar dates, kappa was -0.02 [95% CI -0.08, 0.04]. Simulating the misuse of the method by failing to convert Gregorian dates into lunar did not change the results. We conclude that the CLC method is no better at predicting the sex of a baby than tossing a coin and advise against painting the nursery based on this method's result.

Ovarian cancer is a severe disease with a peak incidence in the older age groups where concurrent morbidity is common and could potentially influence mortality rates.The aim was to study the influence of common comorbidity diagnoses on mortality in ovarian cancer patients.The study population was patients with ovarian cancer in Sweden 1993-2006 (n=11.139) identified in the national Cancer Register. Comorbidity data was obtained from the Patient Register and mortality from Cause of Death Register. Mortality was analyzed with Cox' proportional hazards models and subgroup analyses were performed by age and tumor histology.Almost all of the assessed comorbidities increased mortality in ovarian cancer patients. Thromboembolism was the most hazardous comorbidity (HR=1.95,1 year after cancer diagnosis and HR=7.83, 1-5 years after cancer diagnosis) followed by hematologic complications (HR=1.84 and 7.11 respectively) and infectious disease (HR=1.48 and 5.28 respectively). The occurrence of diabetes mellitus and hypertension had less impact on mortality.Thromboembolism, hematologic complications and infections had a pronounced effect on mortality rates in women with ovarian cancer. The impact of comorbidity was mainly apparent among those with a more prosperous prognosis, such as longer time since cancer diagnosis, less aggressive tumors and younger age.

BackgroundMaternal stress during pregnancy is associated with a modestly increased risk of fetal growth restriction and pre-eclampsia. Since placental abruption shares similar pathophysiological mechanisms and risk factors with fetal growth restriction and pre-eclampsia, we hypothesized that maternal stress may be implicated in abruption risk. We investigated the association between maternal bereavement during pregnancy and placental abruption.MethodWe studied singleton births in Denmark (1978–2008) and Sweden (1973–2006) (n = 5 103 272). In nationwide registries, we obtained data on death of women's close family members (older children, siblings, parents, and partners), abruption and potential confounders.ResultsA total of 30 312 (6/1000) pregnancies in the cohort were diagnosed with placental abruption. Among normotensive women, death of a child the year before or during pregnancy was associated with a 54% increased odds of abruption [95% confidence interval (CI) 1.30–1.82]; the increased odds were restricted to women who lost a child the year before or during the first trimester in pregnancy. In the group with chronic hypertension, death of a child the year before or in the first trimester of pregnancy was associated with eight-fold increased odds of abruption (odds ratio 8.17, 95% CI 3.17–21.10). Death of other relatives was not associated with abruption risk.ConclusionsLoss of a child the year before or in the first trimester of pregnancy was associated with an increased risk of abruption, especially among women with chronic hypertension. Studies are needed to investigate the effect of less severe, but more frequent, sources of stress on placental abruption risk.

The incidence of infantile hypertrophic pyloric stenosis (IHPS) in Sweden decreased dramatically during the 1990s. The aim of the study was to examine IHPS risk factors and the possible change in them as the incidence declined.This is a case-control study including 3608 surgically treated IHPS cases and 17588 matched controls during 1973-2008. Cases were identified in the Swedish National Patient Register and data on possible risk factors were collected from the Swedish Medical Birth Register. The association between study variables and IHPS was analyzed using conditional logistic regression for the whole study period and separately for periods with high and low IHPS incidences.Prematurity (OR, 2.54; 95% CI, 2.06-3.14), caesarean delivery (OR, 1.67; 95% CI, 1.51-1.86), maternal smoking (OR, 1.82; 95% CI, 1.53-2.16), and young maternal age (20yrs) (OR, 1.42; 95% CI, 1.17-1.73) were associated with an increased IHPS risk. Birth order 2 (OR, 0.78; 95% CI, 0.71-0.85) or more was associated with a lower IHPS risk. ORs for smoking increased at low incidence rate.We report caesarean section, prematurity, primiparity, young maternal age, and smoking as significant IHPS risk factors. The impact of smoking was higher during periods with a low incidence.

Objective To investigate whether psoriasis is affected by the use of serotonin reuptake inhibitors (SSRIs). Design A population-based cohort study. Setting The general adult population with plaque psoriasis in Sweden between 1997 and 2006. Subjects A total of 69 830 patients with plaque psoriasis were identified in the National Patient Register. Whether study subjects were exposed to SSRIs was identified through the Swedish Prescribed Drug Register. The SSRI-exposed subjects (n = 1282) had a prescription for SSRIs dispensed twice during 6 months at a Swedish pharmacy between 1 July 2006 and 1 April 2008, with a wash-out period of 1 year or longer. The reference subjects (n = 1282), who were not exposed to SSRIs, were matched for age, county of residence, sex, psoriasis severity and seasonal variation. Main outcome measure Change in psoriasis severity defined by switching between nonsystemic and systemic psoriasis treatments 6 months after exposure to SSRIs. Results The risk of switching from nonsystemic to systemic psoriasis treatments was significantly decreased in the SSRI-exposed group (odds ratio 0.44, 95% confidence interval 0.28–0.68). Conclusion SSRI use in patients with psoriasis is associated with a decreased need for systemic psoriasis treatment.

AIM: To investigate how sociodemographic factors relate to the risk femur shaft fractures in children, and how the relationship differs by gender and age. METHODS: Population based case-control study. Swedish children (n=1,874), 0-14 years of age, with a femur shaft fracture diagnostic code occurring between 1997 and 2005 were selected from the Swedish national inpatient register and compared with matched controls (n=18,740). Demographic, socioeconomic, and injury data were based on record linkage between six Swedish registers. RESULTS: The risk of femur shaft fracture increased for children with younger parents or those living in low-income households. Having a parent with a university education reduced the risk. Stratifying for gender and age group, the association between parents' age was evident only for older boys (7-14 years of age) (OR= 1.40; 95% CI 1.04-1.45), and the association between living in low-income households and fracture rate was only seen in older girls (7-14 years) (OR= 1.50; 95% CI 1.01-2.22). Family composition, number of siblings, birth order or receiving social welfare did not influence the fracture risk. CONCLUSION: Sociodemographic variables influence the rate of femur shaft fractures, in older children the influence differs between boys and girls. ©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica. Language: en

Summary Background The contribution of hereditary factors to the development of diverticular disease (DD) of the colon is unknown. Prevalence and location of diverticula differ in Western world compared to in Asia and several case reports describing families with DD have been published. Aim To assess the heritability of DD in a large population-based sample of twins. Methods The Swedish Twin Registry was cross-linked to the Swedish Inpatient Registry. All twins, born between 1886 and 1980 and not dead before 1969, with a discharge diagnosis of DD were identified. Twins with diagnoses of colon cancer, coeliac disease or non-infectious colitis were excluded to decrease bias. Co-twin odds ratio (OR), concordance rates and tetrachoric correlations were calculated for monozygotic (MZ) and same gender-dizygotic (SS-DZ) twins. Mx-analyses were used to estimate the relative contributions of genetic effects and environmental factors to susceptibility for DD. Calculations were based on both primary and secondary discharge diagnoses to provide estimates reflecting impact of severity of the disease. Results A total of 104 452 twins met the inclusion criteria. Of these, 2296 had a diagnosis of DD. The OR of developing the disease given one's co-twin was affected was 7.15 (95% CI: 4.82–10.61) for MZ and 3.20 (95% CI: 2.21–4.63) for SS-DZ twins. Similarly, concordance rates and tetrachoric correlations were higher in MZ than those in SS-DZ twins. The heritability was estimated to 40% and the non shared environmental effects to 60%. Conclusion Genetic susceptibility is an important component, along with individual specific environmental factors, for the development of diverticular disease of the colon.

Healthcare information provided by telephone service and internet sources is growing but has not been shown to reduce inappropriate emergency department (ED) visits.To describe the use of advice or healthcare information among patients with non-urgent illnesses seeking care before attendance at an ED, or primary care (PC) centres in an urban region in Sweden.Patients with non-urgent illnesses seeking care at an ED or patients attending the PC were followed up with a combination of patient interviews, a questionnaire to the treating physician and a prospective follow-up of healthcare use through a population-based registry.Half of the non-urgent patients attending the ED had used healthcare information or advice before the visit, mainly from a healthcare professional source. In PC, men were more likely to have used information or advice compared with women (OR 2.5 95% CI 1.3 to 5.0), whereas the situation was reversed among ED patients (OR=0.4 95% CI 0.2 to 0.9). Men with no previous healthcare experience attending the ED had the lowest use of healthcare information (p0.01). Very few in both groups had utilised healthcare information on the internet in a case of perceived emergency.ED patients rated as non-urgent by the triage nurse used more advice and healthcare information than PC patients, irrespective of the physician-rated urgency of the symptoms. The problem seems not to be lack of information about appropriate ED use, but to find ways to direct the information to the right target group.

BACKGROUND The surgical treatment of femur shaft fractures in children is changing, and the time spent in hospital is shorter than before. The purpose of this nationwide epidemiology study is to report incidence of pediatric femur shaft fractures in Sweden during 1987 to 2005 by age, sex, cause of injury, severity of injury, and seasonal variation, and to analyze the change in incidence, treatment modalities, and length of hospital stay over time. METHODS Children (N = 4984) with a diagnostic code for femur shaft fracture in Sweden 1987 to 2005 were selected from the Swedish National Hospital Discharge Registry. RESULTS The overall annual incidence per 100,000 children was 22.9 in boys and 9.5 in girls. The incidence declined by 42%, on average 3% per year, from 19.4 to 11.8 between 1987 and 2005 (P < 0.001). The most common cause of injury in children younger than 4 years of age was fall of < 1 m; in children 4 to 12 years of age, sports accidents were the most frequent cause of injury; and in children 13 to 14 years of age, traffic accidents. The month of occurrence for femur shaft fractures had a bimodal seasonal variation with a peak in March and in August. Treatment modalities were changing during the study period from the use of traction to an increased use of external fixation and elastic intramedullary nailing. The length of hospital stay decreased by 81%, from 26 days in 1987 to 5 days in 2005 (P < 0.001), but had no correlation to the introduction of new surgical treatment methods. CONCLUSIONS The present nationwide study of femur shaft fractures shows a decrease of fracture incidence, a shift in the treatment modalities, and shorter length of hospital stay. LEVEL OF EVIDENCE Level III, retrospective comparative study.

Olof Stephansson, Fredrik Granath, Tobias Svensson, Bengt Haglund, Anders Ekbom, Helle KielerClinical Epidemiology Unit and Centre for Pharmacoepidemiology, Department of Medicine, Karolinska University Hospital and Institutet, Stockholm, SwedenPurpose: The purpose of this research is to study drug use during pregnancy in Sweden and agreement between use according to antenatal medical records and dispensed drugs from a pharmacy database.Patients and methods: From the Swedish Medical Birth Register (MBR), we established a population-based cohort of 102,995 women who gave birth in 2007. Using the unique personal registration number, information on dispensed drugs from the Prescribed Drug Register (PDR) was obtained prior to, during, and after the pregnancies and compared with MBR information on drug use from standardized antenatal medical records.Results: According to the PDR, 57.6% of the 102,995 women filled a prescription with at least one drug during pregnancy and 50.9% during the lactating period (until 3 months after delivery). The most dispensed drugs during pregnancy were B-lactam antibacterials and penicillins. Agreement between drugs recorded in antenatal medical records and dispensed drugs was highest for drugs used for chronic conditions. The agreement was particularly high for thyroid therapy (85.3%), anti-intestinal inflammatory drugs (80.3%), antiepileptics (69.2%), immunosuppressants (67.4%), and insulin (63.8%). Agreement for drugs used for occasional use was generally lower, ranging between 42.5% for antihistamines and 0.8% for gynecological anti-infectives.Conclusions: A large proportion of women filled a prescription during pregnancy or the lactating period. Agreement between drug use in medical antenatal records and register information from a national pharmacy database was high for drugs used for chronic conditions but low for occasional use. For occasionally used drugs, medical record and register-based data may provide incomplete exposure information because of nonreporting or noncompliance.Keywords: drug utilization, pregnancy, lactation, pharmacoepidemiology

To compare birth outcomes between women exposed and unexposed to the antiviral medications oseltamivir or zanamivir during pregnancy.This was an observational cohort study including women who gave birth to singletons in Sweden 2005-2007 and their infants. We obtained information from the national health registers and evaluated risks of low Apgar score, small for gestational age (SGA), low birth weight, preterm delivery, congenital malformations, birth-related death (stillbirth and neonatal death combined), and neonatal morbidity by conditional logistic regression. The unexposed [n = 860] were matched to the exposed [n = 86] by birth year and fetal gender.A total of 81 women filled a prescription with oseltamivir only, 2 with zanamivir, and 3 with both oseltamivir and zanamivir. Compared with the unexposed infants, the exposed ones had higher risks of late transient hypoglycemia (crude OR = 4.00, 95%CI: 1.26-12.76). There were no statistical increased risks of low Apgar score, congenital malformations, SGA, low birth weight, preterm birth, or birth-related death. Adjusting for maternal age, parity, smoking, and body mass index had minor effects on the results. None of the women exposed to oseltamivir or zanamivir had been admitted to hospital for influenza during their pregnancy.Except for an increased risk of late transient hypoglycemia, we found no increased risks of adverse birth outcomes among infants exposed to neuraminidase inhibitors in fetal life compared with the unexposed.

We estimated the accuracy of a non-invasive, inexpensive method (the Chinese lunar calendar, CLC) to predict the sex of a baby from around the time of conception, using 2,840,755 singleton births occurring in Sweden between 1973 and 2006. Maternal lunar age and month of conception were estimated, and used to predict each baby's sex, according to a published algorithm. Kappa statistics were estimated for the actual vs. the CLC-predicted sex of the baby. Overall kappa was 0.0002 [95% CI -0.0009, 0.0014]. Accuracy was not modified by year of conception, maternal age, level of education, body mass index or parity. In a validation subset of 1000 births in which we used a website-customised algorithm to estimate lunar dates, kappa was -0.02 [95% CI -0.08, 0.04]. Simulating the misuse of the method by failing to convert Gregorian dates into lunar did not change the results. We conclude that the CLC method is no better at predicting the sex of a baby than tossing a coin and advise against painting the nursery based on this method's result.

Obstetric and neonatal complications have been associated with completed and attempted suicide (suicidal acts) in young offspring. Maternal smoking is one of the most important risk factors for obstetric complications, but the association between prenatal smoking exposure and offspring risk of suicidal acts is unknown. We performed a population-based study of 1,449,333 single births born in Sweden between 1983 and 1996, derived from linked registry data. Maternal smoking and risks of suicidal acts in offspring were estimated using hazard ratios, derived from proportional-hazard models, controlling for potential confounding of parental socio-demographic factors and psychiatric care in first degree relatives. To control for unmeasured familial confounding, a matched case–control analysis of suicidal acts was performed within sibling pairs discordant for prenatal smoking exposure. In the cohort analysis, the adjusted hazard ratio for completed suicide among offspring to women smoking 1–9 cigarettes and at least 10 cigarettes per day were 1.67, 95% confidence interval (CI), 1.29–2.16, and 1.54, 95% CI, 1.12–2.10. For suicidal acts, corresponding hazard ratios were 1.28, 95% CI 1.21–1.35 and 1.48, 95% CI 1.39–1.57, respectively. However, in sibling pairs discordant for suicidal acts and prenatal smoking exposure, we found no evidence that prenatal smoking exposure increased the risk of suicidal acts. We conclude that the association between prenatal smoking exposure and offspring risk of suicidal acts is probably confounded by unmeasured familial factors.

Background A child who suffers a fracture or a soft-tissue injury at a young age faces an increased risk of subsequent injuries during childhood. This risk could be related to personal and family characteristics or to lower-than-average bone-mineral density. The purpose of this nationwide cohort study was to estimate the association between a femur shaft fracture at a young age and the subsequent risk of hospitalization for injuries during childhood. Methods We compared the subsequent risk of hospitalization for injuries during childhood among 1,404 children (exposed) who were one to three years of age when they suffered a femur shaft fracture with the risk among 13,814 randomly selected, gender- and age-matched femur fracture–free children (unexposed). Hazard ratios (HRs) and 95% confidence intervals (CIs) for severe injuries defined as fractures or soft-tissue injuries requiring hospital admission were estimated in a Cox proportional hazards model. Results Exposed children exhibited no significantly increased risk of upper-extremity fractures or soft-tissue injuries during childhood, regardless of sex and follow-up time. Boys exhibited a 162% increased risk of suffering a lower leg fracture requiring hospital admission (HR?=?2.62, 95% CI: 1.45–4.71), but the refracture risk was not significant for girls 2.02 (0.58–6.97). Conclusions We found an increased risk for subsequent fractures in the lower leg that requires inpatient care during childhood for boys, but not for girls, who were one to three years of age when they first suffered a femur shaft fracture. This increased fracture risk is probably not simply the result of greater risk-taking among boys. The explanation might relate to factors affecting the bone quality of the lower leg.

AIMS: To investigate the effects of beta-adrenoceptor stimulation, using the agonist isoprenaline and the antagonist propranolol, on migrating motor complexes in the upper intestine of 16 healthy human volunteers. METHODS: Fasting motility was monitored using a tube with water perfused side holes connected to a pneumohydraulic system. Continuous eight hour recordings were obtained from each volunteer after a 12 hour fasting period. In all experiments, saline was given as control for the first four hour period and beta-adrenergic agents for the next four hours. In separate control studies, saline was given for the whole eight hour period. RESULTS: Isoprenaline (2.5 micrograms/kg/min) reduced the number of activity fronts (phase III) of migrating motor complexes from 3 (2-4) in controls to 1 (0-2) during isoprenaline infusion (p < 0.01). Also, phase II-like activity replaced the regular motility pattern (p < 0.01). By contrast, propranolol (25 micrograms/kg/min) did not induce any significant changes in phase III compared with controls. Saline alone had no effect on motor activity. CONCLUSIONS: Isoprenaline inhibited activity fronts in the human proximal small intestine and induced a postprandial-like motility pattern, whereas propranolol did not affect motor patterns. Stimulation of beta-adrenoceptors is of importance in the control of motor activity of the human small intestine, especially under stressful conditions with high adrenergic activity.

To the Editor,This letter refers to the article “Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia”, by Svensson et al. [1].We thank ...

Objectives To investigate gender and age differences in sociodemographic risk factors and their relationship with femur shaft fractures and injury mechanisms in children. Methods Population based case-control study. Swedish children (N=1,874), aged 0–14 years, with a femur shaft fracture diagnostic code between 1987–2005 were compared to matched controls (N=18,740). Data were based on record linkage between six Swedish registers. Adjusted Odds Ratios were calculated. Results Parental age th percentile, the risk (20%) increased, compared to parents with an income in the 50 th percentile. The risk (50%) was only seen in older girls living in low-income households. Children with at least one university-educated parent reduced their fracture risk (15%), compared to children whose parents had 10–12 years of education, but this decrease could not be linked to gender and age group. Family composition, number of siblings, birth order or receiving social welfare did not influence the fracture risk. Regarding the cause of injury none of the sociodemographic variables influenced the risk equal for boys and girls. Conclusions Sociodemographic differences related to femur shaft fracture rate and cause of injury differ between boys and girls in different age groups. This have implications for parental counselling.

Objective Knowledge about the causes of placental dysfunction disorders is limited. We performed an intergenerational study, focusing on the risks of placental dysfunction disorders in mothers and fathers who had been born small for gestational age (SGA). Study Design Using linked generational data from the Swedish Medical Birth Register from 1973-2006, we identified 321,383 mother-offspring units and 135,637 mother-father-offspring units. Results Compared with mothers who had not been born SGA, mothers who had been born SGA had the following adjusted odds ratios: late preeclampsia, 1.41 (95% confidence interval [CI], 1.26–1.57); early preeclampsia, 1.87 (95% CI, 1.38–2.35); placental abruption, 1.60 (95% CI, 1.23–2.09); spontaneous preterm birth, 1.11 (95% CI, 1.00–1.23); and stillbirth, 1.24 (95% CI, 0.84–1.82). Compared with parents who had not been born SGA, the risk of preeclampsia was more than 3-fold increased if both parents had been born SGA, whereas if only the mother had been born SGA, the corresponding risk was increased by only 50%. Conclusion There is an intergenerational recurrence of placental dysfunction disorders on the maternal side and most likely also on the paternal side.

The effects of two dihydropyridine (DHP) calcium channel antagonists, nifedipine and nimodipine, on migrating myoelectric complexes (MMCs) of the small intestine were studied in naive and morphine-dependent rats. In addition, the effects of two other calcium channel antagonists, verapamil and diltiazem, on the MMCs were investigated. Nifedipine (1.0-4.0 mg kg-1 intravenously) or nimodipine (1.0-4.0 mg kg-1 intravenously) had an inhibitory effect on the spontaneously occurring MMCs, whereas verapamil (2.5-5.0 mg kg-1 intravenously) or diltiazem (2.5-5.0 mg kg-1 intravenously) had no effect. Bay K 8644 (0.25 mg kg-1 intravenously), a DHP calcium channel agonist, instantly reversed the inhibition induced by nifedipine or nimodipine. When given alone, Bay K 8644 induced irregular spiking activity. In morphine-dependent rats with regular MMCs naloxone (1.0 mg kg-1 intravenously) induced intense spiking activity and profuse diarrhea. Nifedipine (2.0 and 4.0 mg kg-1 intravenously) and nimodipine (2.0 and 4.0 mg kg-1 intravenously) given before naloxone prevented the intense, abstinence-evoked spiking and associated diarrhea. In healthy volunteers nimodipine at an infusion rate of 2 mg h-1 for 4 h did not inhibit the fasting motility pattern. Our findings indicate that DHP-binding sites are involved in the regulation of MMC in the rat and that drugs acting as antagonists at these sites can be used to suppress morphine withdrawal diarrhea and, tentatively, other functional disorders of the intestine.