Ninoa Malki

Hormonal and surgical treatments for endometriosis and risk of epithelial ovarian cancer

Whether hormonal or surgical treatment of endometriosis is associated with risk of epithelial ovarian cancer.

Endometriosis as a prognostic factor for cancer survival

Studies have shown an increased risk of malignancies in women with endometriosis. Little is known about the impact of endometriosis on cancer survival. We investigated whether the survival after a diagnosis of a malignancy differs in women with a previously diagnosed endometriosis compared to other women. Women with a first time diagnosis of a malignancy in 1969–2005, were identified using the National Swedish Cancer Register (NSCR). By use of the National Swedish Patient Register (NSPR) we identified all women with a diagnosis of endometriosis during the same period and linked these patients with the data from the NSCR. The cohort comprised 4,278 women with endometriosis and a malignancy, and 41,831 randomly selected matched women without endometriosis. Cox regression was used for all calculations to obtain crude and adjusted cause specific mortality rates, measured as hazard ratios (HR) with 95% confidence intervals (CI). A total of 46,109 women entered the study. There was a statistically significant better survival for women with endometriosis for all malignancies combined (HR = 0.92) and for breast cancer (HR = 0.86) and ovarian cancer (HR = 0.81) specifically. For breast cancer the survival enhancing effect in women with endometriosis decreased with increasing parity. There was poorer survival in malignant melanoma for women with endometriosis (HR = 1.52). The survival in a malignancy is better in women with a previously diagnosed endometriosis compared to women without endometriosis especially for breast and ovarian cancers. The prognosis of malignant melanoma is poorer in women with endometriosis.

Associations Between Birth Characteristics and Eating Disorders Across the Life Course: Findings From 2 Million Males and Females Born in Sweden, 1975–1998

Birth characteristics predict a range of major physical and mental disorders, but findings regarding eating disorders are inconsistent and inconclusive. This total-population Swedish cohort study identified 2,015,862 individuals born in 1975-1998 and followed them for anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified until the end of 2010. We examined associations with multiple family and birth characteristics and conducted within-family analyses to test for maternal-level confounding. In total, 1,019 males and 15,395 females received an eating disorder diagnosis. Anorexia nervosa was independently predicted by multiple birth (adjusted hazard ratio = 1.33, 95% confidence interval: 1.15, 1.53) for twins or triplets vs. singletons) and lower gestational age (adjusted hazard ratio = 0.96, 95% confidence interval: 0.95, 0.98) per extra week of gestation, with a clear dose-response pattern. Within-family analyses provided no evidence of residual maternal-level confounding. Higher birth weight for gestational age showed a strong, positive dose-response association with bulimia nervosa (adjusted hazard ratio = 1.15, 95% confidence interval: 1.09, 1.22, per each standard-deviation increase), again with no evidence of residual maternal-level confounding. We conclude that some perinatal characteristics may play causal, disease-specific roles in the development of eating disorders, including via perinatal variation within the normal range. Further research into the underlying mechanisms is warranted. Finally, several large population-based studies of anorexia nervosa have been conducted in twins; it is possible that these studies considerably overestimate prevalence.

Temporal Trends in Incidence of Myocardial Infarction and Ischemic Stroke by Socioeconomic Position in Sweden 1987–2010

Background We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time. Materials and Methods We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country. Results The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2–1.4) in 1997 to 1.5 (1.4–1.7) in 2010 among men, and from 1.4 (1.3–1.6) in 1997 to 2.1 (1.8–2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women. Conclusion There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

Social Class, Social Mobility and Risk of Psychiatric Disorder - A Population-Based Longitudinal Study

Objectives This study explored how adult social class and social mobility between parental and own adult social class is related to psychiatric disorder. Material and Methods In this prospective cohort study, over 1 million employed Swedes born in 1949-1959 were included. Information on parental class (1960) and own mid-life social class (1980 and 1990) was retrieved from the censuses and categorised as High Non-manual, Low Non-manual, High Manual, Low Manual and Self-employed. After identifying adult class, individuals were followed for psychiatric disorder by first admission of schizophrenia, alcoholism and drug dependency, affective psychosis and neurosis or personality disorder (N=24 659) from the Swedish Patient Register. We used Poisson regression analysis to estimate first admission rates of psychiatric disorder per 100 000 person-years and relative risks (RR) by adult social class (treated as a time-varying covariate). The RRs of psychiatric disorder among the Non-manual and Manual classes were also estimated by magnitude of social mobility. Results The rate of psychiatric disorder was significantly higher among individuals belonging to the Low manual class as compared with the High Non-manual class. Compared to High Non-manual class, the risk for psychiatric disorder ranged from 2.07 (Low Manual class) to 1.38 (Low Non-manual class). Parental class had a minor impact on these estimates. Among the Non-manual and Manual classes, downward mobility was associated with increased risk and upward mobility with decreased risk of psychiatric disorder. In addition, downward mobility was inversely associated with the magnitude of social mobility, independent of parental class. Conclusions Independently of parental social class, the risk of psychiatric disorder increases with increased downward social mobility and decreases with increased upward mobility.

Familial Effects on Ischemic Stroke: The Role of Sibling Kinship, Sex and Age of Onset

Background— Previous studies on familial risk of ischemic stroke have supported genetic influence on the disease incidence. This study aimed to characterize these familial effects in a nationwide population-based study by taking into account sibling relations, sex of siblings, and age of onset, with respect to ischemic stroke incidence. Methods and Results— Incident ischemic stroke cases identified from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007 were linked to their stroke-free siblings (study participants), forming an exposed sib-pair. Each exposed sib-pair was matched up to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar years. Incident ischemic stroke risk was assessed using hazard estimates obtained from stratified Cox regression analyses. A total of 30 735 exposed and 152 391 unexposed study participants were included in the analyses. The overall risk of incident ischemic stroke when exposed was significantly increased (relative risk, 1.61; 95% confidence interval, 1.48–1.75; P <0.001). Familial risk was higher in full (relative risk, 1.64; 95% confidence interval, 1.50–1.81; P <0.001) than in half (relative risk, 1.41; 95% confidence interval, 1.10–1.82; P =0.007) siblings. Familial risk of early ischemic stroke almost doubled when exposed to early ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41–2.67; P <0.001). Conclusions— There was a 60% increased risk for ischemic stroke in individuals having a sibling with prior stroke. The familial effect was even higher for full-sibling relations. Familial effects were observed in both male and female individuals, and no differential effects depending on the sex of either of the siblings were found.Background— Previous studies on familial risk of ischemic stroke have supported genetic influence on the disease incidence. This study aimed to characterize these familial effects in a nationwide population-based study by taking into account sibling relations, sex of siblings, and age of onset, with respect to ischemic stroke incidence. Methods and Results— Incident ischemic stroke cases identified from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007 were linked to their stroke-free siblings (study participants), forming an exposed sib-pair. Each exposed sib-pair was matched up to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar years. Incident ischemic stroke risk was assessed using hazard estimates obtained from stratified Cox regression analyses. A total of 30 735 exposed and 152 391 unexposed study participants were included in the analyses. The overall risk of incident ischemic stroke when exposed was significantly increased (relative risk, 1.61; 95% confidence interval, 1.48–1.75; P<0.001). Familial risk was higher in full (relative risk, 1.64; 95% confidence interval, 1.50–1.81; P<0.001) than in half (relative risk, 1.41; 95% confidence interval, 1.10–1.82; P=0.007) siblings. Familial risk of early ischemic stroke almost doubled when exposed to early ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41–2.67; P<0.001). Conclusions— There was a 60% increased risk for ischemic stroke in individuals having a sibling with prior stroke. The familial effect was even higher for full-sibling relations. Familial effects were observed in both male and female individuals, and no differential effects depending on the sex of either of the siblings were found.

Familial risk of premature cardiovascular mortality and the impact of intergenerational occupational class mobility

The negative impact of low social class on cardiovascular disease (CVD) and mortality has been consistently documented. However, less scientific consistency exists in terms of whether a unique health effect of social mobility from childhood to adulthood prevails. This study explored how childhood and adult social class and the transition between them (social mobility), are related to premature CVD mortality when familial aggregation of CVD among siblings is also considered. The study includes nearly 1.9 million Swedish residents born 1939-1959 distributed over 1,044,725 families, of whom 14,667 died prematurely from CVD in 1990-2003. Information on parental class (1960) and own mid-life occupational class (1990) was retrieved from the respective censuses. Odds ratios for premature CVD mortality according to trajectory-specific social mobility, along with pairwise mean odds ratios for sibling resemblance of premature CVD mortality, were calculated by means of alternating logistic regression. This model calculates the remaining dependency of CVD mortality within sibships after accounting for available risk factors (like parental and adult social class) in the population mean model. Results showed that premature CVD mortality was associated with both parental and own adult social class. A clear tendency for the downwardly mobile to have increased, and for the upwardly mobile to experience a decreased risk of premature CVD mortality was found, as well as a corresponding unique effect of social mobility per se among the manual and non-manual classes. This effect was verified for men, but not for women, when they were analysed separately. The pairwise mean odds ratios for premature CVD mortality among full siblings were 1.78 (95% CI: 1.52-2.08), and were independent of parental CVD mortality and parental or adult occupational class.

Psychiatric disorder and work life: A longitudinal study of intra-generational social mobility.

Background: Intra-generational social mobility, which describes the mobility within an individual’s own working life, is seldom studied among employees with psychiatric disorders (EPD). There is need of knowledge of the intra-generational mobility patterns, in a broader perspective, among EPD. Aims: To investigate intra-generational social mobility in employed individuals diagnosed with affective disorder, personality disorder, schizophrenia and drug dependence in a national Swedish cohort. Method: We identified a national sample of employed Swedish adults born in 1939–1949 (N = 876, 738), and among them individuals with a first-time hospital admission for affective psychosis, neurosis and personality disorder, alcoholism, drug dependence or schizophrenia in 1964–1980 (N = 18, 998). Employed individuals without hospital admission for such diagnoses were utilised as a comparison group (N = 866, 442). Intra-individual social class changes between 1980 and 1990 among EPD and the comparison group were described through summary statistics and graphs. Results: EPD more often held Low manual occupations at baseline in 1980 than the comparison group (44% vs. 28%), although parental social class was similar. In 1990, 19% of EPD and 4% of the comparison group had lost contact with the labour market. Social stability was less common among EPD (49 %) than in the comparison group (67%). Mobility out of the labour force increased and social stability decreased by number of inpatient admissions. Employees diagnosed with affective psychosis or neurosis and personality disorder fared better in the labour market than employees with schizophrenia. Conclusion: Employees suffering from psychiatric disorder do not maintain their social class or remain in the labour force to the same extent as individuals without those problems, irrespective of their parental class. Our results support the social drift hypothesis that individuals with poor psychiatric health move downward in the social hierarchy.

Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Prospective Population-Based Cohort Study.

Background: Recent genome-wide association studies suggest some overlap of genetic determinants of ischemic stroke (IS) and myocardial infarction (MI). This study aimed to assess shared familial risk between IS and MI in a large, population-wide cohort study. Methods: Study participants free of IS and MI and their affected siblings were extracted from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007, forming an exposed sib-pair. They were matched by birth year of both siblings and calendar period to up to five unexposed sib-pairs. Stratified Cox regression analyses were used to assess familial risk of MI and IS in those exposed to having a sibling with IS (n = 31,659) and MI (n = 62,766), respectively, compared to unexposed (n = 143,728 and 265,974). Results: The overall risk of MI when exposed to having a sibling with IS was statistically significantly increased (RR, 1.44; 95% CI, 1.34–1.55, p < 0.001) to a similar extent as risk of IS when exposed to having a sibling with MI (RR, 1.41; 95% CI, 1.32–1.50, p < 0.001). The familial risks were similar in full siblings for both groups (RR for MI, 1.46; 95% CI, 1.35–1.58, p < 0.001; and RR for IS, 1.40; 95% CI, 1.30–1.40, p < 0.001) and half siblings (RR for MI, 1.29; 95% CI, 1.05–1.59, p < 0.001; and RR for IS, 1.38; 95% CI, 1.16–1.65, p < 0.001). Conclusion: This large, population-wide study indicates that there is considerable overlap of familial risk between IS and MI.

PL03 Associations between Birth Characteristics and Eating Disorders Across the Life Course: Findings from two Million Males and Females Born in Sweden 1975-1998

Background Recent years have seen considerable interest in the developmental origins of eating disorders (ED) but results have been conflicting, perhaps reflecting low power in many studies. Limited power has also prevented robust comparisons of associations with ED subtypes or the use of within-family designs to address the potential for confounding. Methods We used total population data to create a cohort of 2,011,908 males and females, born 1975-1998 in Sweden to Swedish-born mothers. Birth characteristics included twin/triplet status; gestational age; birthweight; birth length; premature rupture of the membranes; delivery method; Apgar score at 5 minutes; birth traumas; mother’s smoking during pregnancy; and mother’s weight gain during pregnancy. We adjusted for multiple family and social characteristics, and conducted within-family analyses to test for confounding at the maternal/family level. Our outcomes were hospitalisation for anorexia, bulimia or eating disorder not-otherwise-specified (EDNOS)’ after age 12, with follow-up period until end 2010. Results Anorexia was independently predicted by multiple birth (AOR 1.33 [95% CI 1.15, 1.53] for twin/triplet vs. singleton) and lower gestational age (HR 0.96 [0.95, 0.98] per extra week of gestation). Gestational age showed a clear dose-response pattern. These associations were largely specific to anorexia, and were only seen in the cohort members affected; within-family analyses revealed that the maternal siblings of twins or preterm individuals showed no increased risk, and provided no evidence of residual maternal-level confounding. Higher birthweight for gestational age showed a strong, positive dose-response association with bulimia (HR 1.15 [1.09, 1.22]) per sex-standardised standard deviation increase). Again, this association was specific to bulimia and within-family analyses provided no evidence of residual confounding. By contrast, although mother’s smoking predicted anorexia, this did seem likely to reflect maternal-level confounding. Other birth characteristics showed little or no association with any ED outcome, except a trend towards increased bulimia and EDNOS among mothers who gained excessive weight during pregnancy. Conclusion These findings are consistent with a causal role of earlier gestational age upon anorexia and higher birthweight upon bulimia. Further research is needed to elucidate the mechanisms, but the dose-response nature of these associations indicates that they do not simply reflect pathological responses at the extremes of the distribution. The strong association with multiple births is noteworthy as many of the largest population-based studies of ED prevalence have been conducted in twins: our findings suggest the possibility that such studies substantially overestimate ED prevalence.