Deconstructing the smoking-preeclampsia paradox through a counterfactual framework.

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery ( 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes

Mental disorders around cancer diagnosis and increased hospital admission rate - a nationwide cohort study of Swedish cancer patients

Background: Whether the emotional distress around cancer diagnosis is associated with the long-term outcomes and care utilization is unknown. We aimed to examine the association of mental disorders around cancer diagnosis with the hospital admission rates of cancer patients thereafter. Methods: We conducted a nationwide cohort study including 218,508 cancer patients diagnosed in Sweden during 2004–2009 and followed them from 90 days after cancer through 2010. We used a clinical diagnosis of stress-related mental disorders from 90 days before to 90 days after cancer diagnosis as the exposure. We studied first all hospital admissions and then separately three common admissions, including external injuries, infections, and cardiovascular diseases. The Cox model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Four thousand one hundred five patients received a diagnosis of stress-related mental disorders around the cancer diagnosis, and experienced a 35% increased rate of any hospital admission during follow-up (HR: 1.35, 95%CI: 1.28–1.41) as well as hospital admissions for external injuries (HR: 1.89, 95%CI: 1.67–2.14), infections (HR: 1.28, 95%CI: 1.08–1.52), and cardiovascular diseases (HR: 1.16, 95%CI: 1.03–1.30). Similar association was noted for most common cancer types. Conclusions: These data suggest that cancer patients diagnosed with a stress-related mental disorder immediately before or after cancer diagnosis are subsequently at increased risk of hospital admissions for major comorbidities of cancer. Electronic supplementary material The online version of this article (10.1186/s12885-018-4270-4) contains supplementary material, which is available to authorized users

Waiting time for cancer treatment and mental health among patients with newly diagnosed esophageal or gastric cancer: a nationwide cohort study

Background Except for overall survival, whether or not waiting time for treatment could influences other domains of cancer patients’ overall well-being is to a large extent unknown. Therefore, we performed this study to determine the effect of waiting time for cancer treatment on the mental health of patients with esophageal or gastric cancer. Methods Based on the Swedish National Quality Register for Esophageal and Gastric Cancers (NREV), we followed 7,080 patients diagnosed 2006–2012 from the time of treatment decision. Waiting time for treatment was defined as the interval between diagnosis and treatment decision, and was classified into quartiles. Mental disorders were identified by either clinical diagnosis through hospital visit or prescription of psychiatric medications. For patients without any mental disorder before treatment, the association between waiting time and subsequent onset of mental disorders was assessed by hazard ratios (HRs) with 95% confidence interval (CI), derived from multivariable-adjusted Cox model. For patients with a preexisting mental disorder, we compared the rate of psychiatric care by different waiting times, allowing for repeated events. Results Among 4,120 patients without any preexisting mental disorder, lower risk of new onset mental disorders was noted for patients with longer waiting times, i.e. 18–29 days (HR 0.86; 95% CI 0.74-1.00) and 30–60 days (HR 0.79; 95% CI 0.67-0.93) as compared with 9–17 days. Among 2,312 patients with preexisting mental disorders, longer waiting time was associated with more frequent psychiatric hospital care during the first year after treatment (37.5% higher rate per quartile increase in waiting time; p for trend = 0.0002). However, no such association was observed beyond one year nor for the prescription of psychiatric medications. Conclusions These data suggest that waiting time to treatment for esophageal or gastric cancer may have different mental health consequences for patients depending on their past psychiatric vulnerabilities. Our study sheds further light on the complexity of waiting time management, and calls for a comprehensive strategy that takes into account different domains of patient well-being in addition to the overall survival.This study was partly supported by the Swedish Cancer Society (grant No: CAN 2014/417).Peer Reviewe

Risk of psychiatric disorders among the surviving twins after a co-twin loss

Publisher's version (útgefin grein)Losing a co-twin by death is a severely stressful event yet with unknown impact on the surviving twin’s risk of psychiatric disorders. We identified all Swedish-born twins who lost a cotwin by death between 1973 and 2013 (n = 4,528), their 4939 non-twin full siblings, together with 22,640 age-and sex-matched non-bereaved twins. Compared to the non-bereaved twins, exposed twins were at increased risk of receiving a first diagnosis of psychiatric disorders (hazard ratio = 1.65, 95% confidence interval1.48–1.83), particularly during the first month after loss. Similarly, compared to non-twin full siblings, the relative risks were significantly increased after loss of monozygotic co-twin (2.45-fold), and loss of a dizygotic co-twin (1.29-fold), with higher HR observed with greater age gaps between twins and non-twin siblings. As dizygotic twins share equal genetic relatedness to the deceased twin as their full siblings, this pattern suggests that beyond the contribution of genetic factors, shared early life experiences and attachment contribute to the risk of psychiatric disorders among surviving twins after co-twin loss.The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council.Peer Reviewe

Nordic health registry-based research: A review of health care systems and key registries

The Nordic countries are Denmark, Finland, Iceland, Norway, and Sweden and comprise a total population of approximately 27 million. The countries provide unique opportunities for joint health registry-based research in large populations with long and complete follow-up, facilitated by shared features, such as the tax-funded and public health care systems, the similar population-based registries, and the personal identity number as unique identifier of all citizens. In this review, we provide an introduction to the health care systems, key registries, and how to navigate the practical and ethical aspects of setting up such studies. For each country, we provide an overview of population statistics and health care expenditures, and describe the operational and administrative organization of the health care system. The Nordic registries provide population-based, routine, and prospective data on individuals lives and health with virtually complete follow-up and exact censoring information. We briefly describe the total population registries, birth registries, patient registries, cancer registries, prescription registries, and causes of death registries with a focus on period of coverage, selected key variables, and potential limitations. Lastly, we discuss some practical and legal perspectives. The potential of joint research is not fully exploited, mainly due to legal and practical difficulties in, for example, cross-border sharing of data. Future tasks include clear and transparent legal pathways and a framework by which practical aspects are facilitated.</p

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

Objective: To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. Design: Population based cohort study using data from the national health registers. Setting: Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. Participants: More than 1.6 million infants born after gestational week 33. Main outcome measures: Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. Results: Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). Conclusions: The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.publishedVersio

Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients

Publisher's version (útgefin grein)Background: β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014. Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures. Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72–0.94); p =.005]. Statistically significant associations were observed for non-selective [0.71 (0.55–0.91); p =.006], β1-receptor selective [0.86 [0.75–1.00); p =.049] and lipophilic [0.78 (0.67–0.90); p =.001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80–1.28); p =.906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67–1.01); p =.062]. Conclusion: β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.This work was supported by a grant from the Swedish Cancer Society (CAN 2013/650). Dr Karin E. Smedby has research funding from Janssen.Peer Reviewe

Association of Maternal Autoimmune Diseases With Risk of Mental Disorders in Offspring in Denmark

IMPORTANCE Maternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood.OBJECTIVE To investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood.DESIGN, SETTING, AND PARTICIPANTS This population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021.EXPOSURES Maternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register.MAIN OUTCOMES AND MEASURES The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders.RESULTS Of the 2 254 234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05436]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-121), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08436] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]).CONCLUSIONS AND RELEVANCE In this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.</p

Early Life Residence, Fish Consumption, and Risk of Breast Cancer.

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open To access publisher's full text version of this article click on the hyperlink at the bottom of the pageBackground: Little is known about fish intake throughout the life course and the risk of breast cancer.Methods: We used data on the first residence of 9,340 women born 1908 to 1935 in the Reykjavik Study as well as food frequency data for different periods of life from a subgroup of the cohort entering the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (n = 2,882).Results: During a mean follow-up of 27.3 years, 744 women were diagnosed with breast cancer in the Reykjavik Study. An inverse association of breast cancer was observed among women who lived through the puberty period in coastal villages, compared with women residing in the capital area [HR, 0.78; 95% confidence interval (CI), 0.61-0.99]. In the subgroup analysis of this Icelandic population, generally characterized by high fish intake, we found an indication of lower risk of breast cancer among women with high fish consumption (more than 4 portions per week) in adolescence (HR, 0.71; 95% CI, 0.44-1.13) and midlife (HR, 0.46; 95% CI, 0.22-0.97), compared with low consumers (2 portions per week or less). No association was found for fish liver oil consumption in any time period, which could be due to lack of a reference group with low omega-3 fatty acids intake in the study group.Conclusions: Our findings suggest that very high fish consumption in early to midlife may be associated with a reduced risk of breast cancer.Impact: Very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 346-54. ©2016 AACR.NIH Intramural Research Program of the National Institute on Aging Icelandic Heart Association Icelandic Parliament Icelandic Centre for Research, RANNIS Public Health Fund of the Icelandic Directorate of Healt

Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study

Publisher's version (útgefin grein)Background: Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown. Methods: We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis. Results: Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98). Conclusion: Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.This study was supported by grants awarded to FF by Swedish Cancer Society (No. CAN 2017/322) and the Swedish Research Council for Health, Working Life and Welfare (No. 2017-00531), to KH by China Scholarship Council (No. 201806240005), to ES by National Health and Medical Research Council (GNT1147498) and National Breast Cancer Foundation (IIRS-20 to 025), and to AW by the National Breast Cancer Foundation (PF-15 to 014). The researchers were independent of the funding agencies. The funding bodies have no role in the design of the study or collection, analysis, and interpretation of data or in writing the manuscript. Open access funding provided by Karolinska Institute.Peer Reviewe