The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study.

BACKGROUND: Few previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture. METHODS: Individual-level data on medications dispensed from pharmacies (2005-2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006-2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model. RESULTS: During 2006-2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1-5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21-25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51-65 years. CONCLUSIONS: Rx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.

BCG vaccination and multiple sclerosis risk: A Norwegian cohort study.

INTRODUCTION: Bacillus Calmette-Guérin (BCG) vaccination induces long-lasting effects on the adaptive and innate immune systems and prevents development of experimental autoimmune encephalomyelitis and possibly also inflammatory disease activity in multiple sclerosis (MS). OBJECTIVE: The objective is to examine if BCG given in early adulthood decreases MS risk. METHODS: From 791,369 (52% females) Norwegians participating in a national tuberculosis screening program from 1963 to 1975, we collected information on BCG vaccination and tuberculosis disease status. Later, MS disease was ascertained through both the Norwegian MS Registry and Biobank and the Norwegian Death Registry. We used logistic regression models to assess the relationship between BCG vaccination and MS risk. RESULTS: In those BCG vaccinated, mean age at vaccination was 15.6 (standard deviation (SD) = 5.5) years. A total of 2862 (65% females) MS cases were retrieved. Overall, we found no association between MS risk and BCG vaccination. Compared to non-BCG-vaccinated individuals with no signs of tuberculosis infection, odds ratio (OR) for MS was 1.00 (95% confidence interval (CI) = 0.80-1.25) in the BCG-vaccinated group. In those not BCG vaccinated because of latent tuberculosis infection, the corresponding OR was 0.86 (95% CI = 0.66-1.13). CONCLUSION: We found no evidence of BCG vaccination or latent tuberculosis infection in young adulthood being linked to MS risk.

The hidden burden of dysmenorrhea among adolescent girls in Palestine refugee camps: a focus on well-being and academic performance.

BACKGROUND: Dysmenorrhea (painful menstruation) is a condition that may have a profound effect on adolescent girls' health status and well-being. It can impede their engagement in daily activities and hamper their regular school attendance. This study aims to explore the relationship between dysmenorrhea, well-being, and academic performance among adolescent girls living in Palestine refugee camps in the West Bank and Jordan. METHODS: We conducted a household survey between June and September 2019, with a total sample of 2737 adolescent girls 15 to 18 years old. Dysmenorrhea severity was assessed using the Working Ability, Location, Intensity, Duration of pain Dysmenorrhea scale (WaLIDD). The WHO-5 scale was used to evaluate the girls' overall well-being. Menstrual academic disruption (MAD) was measured using a self-reported scale. Multiple linear regression models were employed to evaluate the association between dysmenorrhea, well-being, and academic performance. Directed Acyclic Graphs (DAGs) were employed to identify variables for control in regression models. RESULTS: The mean dysmenorrhea score was 6.6 ± 2.6, with 37.9% and 41.2% expressing moderate and severe symptoms, respectively. The mean WHO-5 score was 58.7 ± 25.1, and 34.9% reported a low well-being status. The mean MAD score was 3.1 ± 3.3. 26% reported missing school due to dysmenorrhea, 36% said dysmenorrhea impacted their ability to concentrate, and 39% were unable to study for tests, and complete homework. The first regression analysis showed a reduction of 1.45 units in WHO-5 score for each unit increase in dysmenorrhea. The second regression analysis showed a non-linear increase in MAD score for increasing dysmenorrhea. For each dysmenorrhea score less than 4 (mild) there was a modest increase in MAD scores (coefficient 0.08, p-value = 0.006), and for each dysmenorrhea score above 4 there was a stronger increase in MAD scores (coefficient 0.95, p < 0.001). CONCLUSION: Dysmenorrhea poses significant challenges to the well-being and academic performance of adolescent girls living in Palestine refugee camps. Collaborative efforts and multifaceted approaches are crucial to address dysmenorrhea effectively. This involves research, targeted interventions, culturally sensitive strategies, and fostering a supportive environment that empowers girls to thrive academically and beyond.

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

We investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures. PURPOSE: To investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index. METHODS: Norwegian women aged 50-89 in 2005-2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis. RESULTS: Of 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91-0.99) for bisphosphonate use and 0.60 (95% CI: 0.47-0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29-0.61) compared with the unexposed population. CONCLUSIONS: In population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.

Adjusting for outcome risk factors in immigrant datasets: total or direct effects?

BACKGROUND: When quantifying differences in health outcomes between immigrants and non-immigrants, it is common practice to adjust for observed differences in outcome risk factors between the groups being compared. However, as some of these outcome risk factors may act as mediators on the causal path between the exposure and outcome, adjusting for these may remove effects of factors that characterize the immigrants rather than removing a bias between immigrants and non-immigrants. METHODS: This study investigates the underlying conditions for which adjusting for outcome risk factors in regression models can lead to the estimation of either total or direct effect for the difference in health outcomes between immigrants and non-immigrants. For this investigation, we use modern tools in causal inference to construct causal models that we believe are highly relevant in an immigrant dataset. In these models, the outcome risk factor is modeled either as a mediator, a selection factor, or a combined mediator/selection factor. Unlike mediators, selection factors are variables that affect the probability of being in the immigrant dataset and may contribute to a bias when comparing immigrants and non-immigrants. RESULTS: When the outcome risk factor acts both as a mediator and selection factor, the adjustment for the risk factor in regression models leads to the estimation of what is known as a "controlled" direct effect. When the outcome risk factor is either a selection factor or a mediator alone, the adjustment for the risk factor in regression models leads to the estimation of a total effect or a controlled direct effect, respectively. In all regression analyses, also adjusting for various confounding paths, including mediator-outcome confounding, may be necessary to obtain valid controlled direct effects or total effects. CONCLUSIONS: Depending on the causal role of the outcome risk factors in immigrant datasets, regression adjustment for these may result in the estimation of either total effects or controlled direct effects for the difference in outcomes between immigrants and non-immigrants. Because total and controlled direct effects are interpreted differently, we advise researchers to clarify to the readers which types of effects are presented when adjusting for outcome risk factors in immigrant datasets.

Trajectories of ADHD medication use before, during, and after pregnancy: A population-based study from Norway and Sweden.

PURPOSE: To describe ADHD medication use trajectories around pregnancy in Norway and Sweden. METHODS: We identified pregnancies resulting in births using linked data from birth and prescribed drug registers of Norway (2006-2019, N = 813 107) and Sweden (2007-2018, N = 1 269 146). We restricted to women who filled prescriptions for ADHD medication during pregnancy or in the year before or after. We described exposure as use versus no use, and total amount of drug dispensed in defined daily doses (DDDs). Group-based trajectory modeling was used to identify distinct medication use trajectories. RESULTS: In total, 13 286 women (0.64%) filled a prescription for ADHD medication. We identified four trajectory groups: continuers (5.7%), interrupters (23.8%), discontinuers (49.5%), and late initiators (21.0%). Discontinuers were younger, continuers were older on average. More women continued medication in recent years (2014-2019). Most discontinuers (60.7%) were nulliparous; more initiators and continuers had one or multiple previous births, respectively. Continuers were least likely to live with a partner (65.8%). Discontinuers were least likely (24.7%) and continuers most likely (37.6%) to smoke at the beginning of pregnancy. More continuers used amphetamine derivatives and were most likely to use other psychotropics. On modeling continuers, we identified three dose-trajectory groups which suggested that most women reduced medication dose during pregnancy. CONCLUSIONS: Most pregnant women discontinued or interrupted their ADHD medication during pregnancy, but more continued in recent years. Continuers were more likely to have had previous births, less likely to have lived with a partner, and may have had additional comorbidities warranting the use of other psychotropics.

Aryl hydrocarbon receptor activity in human breast milk and cryptorchidism: A case-control study within the prospective Norwegian HUMIS cohort.

BACKGROUND: The etiology of cryptorchidism remains poorly understood. Endocrine disrupting chemicals can impact estrogen signaling by interacting with aryl hydrocarbon receptor (AhR) activity. OBJECTIVE: To evaluate whether AhR activity in breast milk samples is associated with cryptorchidism. METHOD: We conducted a case-control study based on 199 mother-child pairs (n = 91 cases/108 controls) selected from the Norwegian Human Milk Study (2002-2009). We defined cases for cryptorchidism based on maternal reports at 1-, 6-, 12-, and 24- months after birth. Chemically- and biologically stable AhR activity (pg 2,3,7,8-TCDD equivalent (TEQ)/g lipid) was determined by DR- CALUX® assay in the mothers' milk collected at a median of 33 (10th-90th percentile: 18-57) days after delivery. We used multivariate logistic regression to compare AhR activity levels between cases and controls, and linear regression separately, to establish the relationship with the presence of 27 potential EDCs measured in breast milk and AhR activity. RESULTS: The average estimated daily intake (EDI) of dioxin and (dioxin-like (dl)-compounds via breast milk is 33.7 ± 17.9 pg TEQ/kg bodyweight per day among Norwegian children. There were no significant differences in AhR activation in breast milk samples between cases with cryptorchidism and controls. Among the 27 chemicals measured in breast milk, AhR activity was (borderline) significantly associated with all dl-PCBs, three non-dioxin-like (ndl)-PCBs (PCB-74, PCB-180, PCB-194) and two organochlorine pesticides (OCPs; HCB, ß-HCH). No associations between AhR activity and brominated flame retardants (PBDEs) or poly- and perfluoroalkyl substances (PFASs). CONCLUSION: No association between AhR activity and cryptorchidism was found among Norwegian boys. The average EDI of dioxin and dl-compounds in exclusively breastfed Norwegian infants remains above the safety threshold and, therefore requires further reduction measures. Consistent with a possible role in the observed AhR activity, all dl-PCBs were associated with AhR activity whereas the association was null for either PBDEs or PFASs.

Lipid and lipoprotein concentrations during pregnancy and associations with ethnicity.

BACKGROUND: To describe ethnic differences in concentrations of lipids and lipoproteins, and their changes, during pregnancy to postpartum. METHODS: This was a population-based cohort study conducted in primary antenatal care in Norway. The participants (n = 806) were healthy, pregnant women, 59% were ethnic minorities. Outcomes were triglycerides, total cholesterol, HDL- and LDL-cholesterol, analysed from fasting blood samples drawn at gestational age (weeks) 15, 28 and 14 weeks postpartum. We performed linear regression models and linear mixed models to explore the total effect of ethnicity on the outcomes, adjusting for gestational age /week postpartum, maternal age and education. The analyses are corrected for multiple testing using the Bonferroni correction. RESULTS: At gestational age 15, triglyceride concentrations were lower in women of African origin (1.03 mmol/mol (95% CI: 0.90, 1.16)) and higher in women of South Asian (primarily Pakistan and Sri Lanka) origin (1.42 mmol/mol (1.35, 1.49)) and East Asian (primarily Vietnam, Philippines and Thailand) origin (1.58 mmol/mol (1.43, 1.73)) compared with Western Europeans (1.26 mmol/mol (1.20, 1.32)). Women of Asian and African origin had a smaller increase in triglycerides, LDL- and total cholesterol from gestational age 15 to 28. At gestational age 28, LDL-cholesterol levels were lowest among East Asians (3.03 mmol/mol (2.72, 3.34)) compared with Western Europeans (3.62 mmol/mol (3.50, 3.74)). Triglycerides and HDL-cholesterol were lower postpartum than at gestational age 15 in all groups, but the concentration of LDL-cholesterol was higher, except in Africans. South and East Asian women had lower HDL-cholesterol and higher triglycerides postpartum, while African women had lower triglycerides than Western Europeans. CONCLUSION: We found significant differences in the concentrations of lipids and lipoproteins and their changes during pregnancy and the early postpartum period related to ethnic origin.

Risk factors for revision surgery due to dislocation within 1 year after 111,711 primary total hip arthroplasties from 2005 to 2019: a study from the Norwegian Arthroplasty Register.

BACKGROUND AND PURPOSE: Dislocation of a hip prosthesis is the 3rd most frequent cause (after loosening and infection) for hip revision in Norway. Recently there has been a shift in surgical practice including preferred head size, surgical approach, articulation, and fixation. We explored factors associated with the risk of revision due to dislocation within 1 year and analyzed the impact of changes in surgical practice. PATIENTS AND METHODS: 111,711 cases of primary total hip arthroplasty (THA) from the Norwegian Arthroplasty Register were included (2005-2019) after primary THA with either 28 mm, 32 mm, or 36 mm femoral heads, or dualmobility articulations. A flexible parametric survival model was used to calculate hazard ratios for risk factors. Kaplan-Meier survival rates were calculated. RESULTS: There was an increased risk of revision due to dislocation with 28 mm femoral heads (HR 2.6, 95% CI 2.0-3.3) compared with 32 mm heads. Furthermore, there was a reduced risk of cemented fixation (HR 0.6, CI 0.5-0.8) and reverse hybrid (HR 0.6, CI 0.5-0.8) compared with uncemented. Also, both anterolateral (HR 0.5, CI 0.4-0.7) and lateral (HR 0.6, CI 0.5-0.7) approaches were associated with a reduced risk compared with the posterior approach. The time-period 2010-2014 had the lowest risk of revision due to dislocation. The trend during the study period was towards using larger head sizes, a posterior approach, and uncemented fixation for primary THA. INTERPRETATION: Patients with 28 mm head size, a posterior approach, or uncemented fixation had an increased risk of revision due to dislocation within 1 year after primary THA. The shift from lateral to posterior approach and more uncemented fixation was a plausible explanation for the increased risk of revision due to dislocation observed in the most recent time-period. The increased risk of revision due to dislocation was not fully compensated for by increasing femoral head size from 28 to 32 mm.

Explaining better hearing in Norway: a comparison of two cohorts 20 years apart - the HUNT study.

BACKGROUND: The hearing function at a given age seems to have improved in more recent born cohorts in industrialized countries. But the reasons for the improvement have not yet been explained. METHODS: We investigated the extent to which better hearing in Norway is attributed to modifiable risk factors by using representative demographic and audiometric data from two cohorts of the Trøndelag Health Study, HUNT2 (1996-1998) and HUNT4 (2017-2019). We estimated natural indirect effects using causal inference methods in order to assess whether cohort improvement in hearing thresholds (HTs) was mediated by occupational noise exposure, recurrent ear infections, smoking and education. RESULTS: The improvement in HTs from HUNT2 to HUNT4 was 2.8 and 3.0 dB at low respectively high frequencies. Together all risk factors mediated this improvement by 0.8 dB (95% CI 0.7-0.9) and 0.8 dB (95% CI 0.7-0.9) respectively, corresponding to mediated proportions of 27 and 28%. Substantial mediation was specifically found for occupational noise in men and recurrent ear infections in women (mediated proportions of 11 and 17% at high frequencies, respectively). CONCLUSIONS: Increased education, less occupational noise exposure, ear infections and smoking contributed considerably to better hearing in Norway the last two decades.

Is the Association of Early Day Care Attendance with Childhood Asthma Explained by Underlying Susceptibility?

BACKGROUND: Previous studies of early day care attendance and asthma development are inconsistent, which may be explained by inadequate control of confounding and effect modification. We examined the effect of early day care on the risk of asthma taking into account the underlying susceptibility to asthma. METHODS: The study included 55,404 children participating in the Norwegian Mother, Father and Child Cohort Study. Asthma at age 7 was defined by dispensed asthma medications in the Norwegian Prescription Database. We defined a disease risk score (DRS) to account for an underlying susceptibility to asthma including a range of hereditary and nonhereditary predictors of asthma. We assessed confounding and modifying effects of DRS on the association between day care and asthma. RESULTS: Day care before 18 months was associated with a lower risk of asthma by age 7 (adjusted risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.78, 0.92) when compared with home care. DRS modified the estimated effect of day care on asthma risk. Among the 80% of children with DRS between 0.03 and 0.16, day care was associated with a reduced asthma risk (RRs between 0.79 and 0.87), whereas among 0.5% of children with a high DRS (above 0.28), estimated effect of day care on asthma increased gradually (RR for the highest DRS 2.2; 1.0-4.9). CONCLUSIONS: In our study, among most children, early day care was associated with reduced asthma risk at 7 years, and increased risk in a small group of children with very high underlying susceptibility to asthma.

The prevalence of mental distress and the association with education: a cross-sectional study of 18-49-year-old citizens of Yangon Region, Myanmar.

BACKGROUND: Poor mental health is an important contributor to the global burden of disease. Mental health problems are often neglected in communities, and are scarcely studied in developing countries, including Myanmar. This study estimates the prevalence of mental distress by socio-demographic and health related factors, and the association between education and mental distress. As far as the authors are aware, this is the first population-based study in Myanmar estimating the prevalence of mental distress. METHODS: Between October and November 2016, a cross sectional study was conducted using a multi-stage sampling design with face-to-face interviews using the Hopkins Symptom Checklist (HSCL-10) for mental distress (symptoms of depression and anxiety). The multivariable analysis strategy was based on Directed Acyclic Graphs (DAGs), to identify confounders, mediators and colliders. Pearson's chi-square was used for testing differences between proportions and multiple linear regression analysis was applied to explore the association between education (years at school) and mental distress (HSCL score). RESULTS: A random sample of 2391 (99.6% response) men and women aged 18-49 years participated in the study. The prevalence of mental distress was 18.0% (95% confidence interval (CI): 14.7-21.9), being higher among women (21.2%; 95% (CI): 16.6-26.6) than men (14.9%; 95% (CI): 11.4-19.2). Older-age, being separated or divorced and having a higher number of children were associated with increased mental distress. In linear regression analyses, adjusted for confounders (age, marital status and income), there was a significant negative association between years at school and mental distress among women and older men (> 30 years), but not among the youngest men. CONCLUSIONS: The prevalence of mental distress is high, and there is an association between HSCL-10 score and education. Due to the scarcity of mental health services in Myanmar, the findings indicate a need for a mental health policy to handle the burden of mental health problems in Yangon, a burden which is probably high within the country.

Preeclampsia and Hypertension During Pregnancy in Areas with Relatively Low Levels of Traffic Air Pollution.

Objectives Air pollution exposure may contribute to the development of preeclampsia and hypertension during pregnancy. However, the evidence for such a relation is still limited. We investigated the associations between exposure for moderate to low levels of air pollution during pregnancy and preeclampsia and gestational hypertension in selected urban and county areas of Norway. Methods This study used a sub-group of 17,533 women in the Norwegian Mother and Child Cohort Study. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy. Information on preeclampsia and gestational hypertension were obtained from the Medical Birth Registry of Norway and information on lifestyle factors was collected from questionnaires completed by the women during pregnancy. Results Moderate mean levels of NO2 (13.6 ± 6.9 µg/m3) at residential address during pregnancy were not associated with preeclampsia and pregnancy hypertension. We found no statistically significant associations per 10 µg/m3 change in NO2 exposure and preeclampsia (adjusted OR 0.89, 95% CI 0.74, 1.08) or hypertension during pregnancy (adjusted OR 0.91, 95% CI 0.78, 1.06). Conclusions for Practice In this large Norwegian pregnancy cohort, we found no statistically significant associations for moderate to low levels of pregnancy NO2 exposure and preeclampsia or hypertension during pregnancy.

Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.

BACKGROUND/AIMS: Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity. METHODS: We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status. RESULTS: Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, ß-hexachlorocyclohexane (ß-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in ß-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of ß-HCH showed reduced infant growth (ß = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. CONCLUSIONS: Our results suggest that early life ß-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal ß-HCH exposure.

The educational gradient in cardiovascular risk factors: impact of shared family factors in 228,346 Norwegian siblings.

BACKGROUND: Various indicators of childhood socioeconomic position have been related to cardiovascular disease (CVD) risk in adulthood. We investigated the impact of shared family factors on the educational gradient in midlife CVD risk factors by assessing within sibling similarities in the gradient using a discordant sibling design. METHODS: Norwegian health survey data (1980-2003) was linked to educational and generational data. Participants with a full sibling in the health surveys (228,346 individuals in 98,046 sibships) were included. Associations between attained educational level (7-9 years, 10-11 years, 12 years, 13-16 years, or >16 years) and CVD risk factor levels in the study population was compared with the corresponding associations within siblings. RESULTS: Educational gradients in risk factors were attenuated when factors shared by siblings was taken into account: A one category lower educational level was associated with 0.7 (95% confidence interval 0.6 to 0.8) mm Hg higher systolic blood pressure (27% attenuation), 0.4 (0.4 to 0.5) mmHg higher diastolic blood pressure (30%), 1.0 (1.0 to 1.1) more beats per minute higher heart rate (21%), 0.07 (0.06 to 0.07) mmol/l higher serum total cholesterol (32%), 0.2 (0.2 to 0.2) higher smoking level (5 categories) (30%), 0.15 (0.13 to 0.17) kg/m2 higher BMI (43%), and 0.2 (0.2 to 0.2) cm lower height (52%). Attenuation increased with shorter age-difference between siblings. CONCLUSION: About one third of the educational gradients in modifiable CVD risk factors may be explained by factors that siblings share. This implies that childhood environment is important for the prevention of CVD.

Changes in prevalence, awareness, treatment and control of hypertension from 2004 to 2014 among 25-74-year-old citizens in the Yangon Region, Myanmar.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases, and little is known about trends in prevalence, awareness, treatment and the control of hypertension in Myanmar. This study aims at evaluating changes from 2004 to 2014 in the prevalence, awareness, treatment and control of hypertension in the Yangon Region, Myanmar, and to compare associations between hypertension and selected socio-demographic, behavioural- and metabolic risk factors in 2004 and 2014. METHODS: In 2004 and 2014, household-based cross-sectional studies were conducted in urban and rural areas of Yangon Region using the WHO STEPS protocol. Through a multi-stage cluster sampling method, a total of 4448 and 1486 participated in 2004 and 2014, respectively, with the response rates above 89%. RESULTS: From 2004 to 2014, there was a significant increase in the age-standardized prevalence of hypertension from 26.7% (95% CI:24.4-29.1) - 34.6% (32.2-37.1), as well as an awareness from 19.4% (17.2-21.9) to 27.8% (24.9-31.0), while treatment and control rates did not change. The age-standardized mean systolic blood pressure increased from 122.8 (SE) ± 0.82 mmHg in 2004 to 128.1 ± 0.53 mmHg in 2014, whereas diastolic blood pressure increased from 76.2 ± 0.35 mmHg to 80.9 ± 0.53 mmHg. In multivariate analyses, hypertension was significantly associated with age, alcohol consumption, overweight and diabetes in both 2004 and 2014, and additionally associated with low physical activity and hypercholesterolemia in 2004. Combining all data, a significant association between study-year and hypertension persisted in different models with an adjustment for socio-demographic variables and behavioural variables, but not when adjusting for a combination of socio-demographic variables, the metabolic variables, BMI and hypercholesterolemia. CONCLUSION: The prevalence of hypertension has risen from 2004 to 2014 in both urban and rural areas of the Yangon Region, while, the awareness, treatment and control rate of hypertension remains low in urban and rural areas among both males and females. It is likely that changes in the metabolic variables, BMI and hypercholesterolemia have contributed to an increase in the prevalence of hypertension from 2004 to 2014. Factors associated with hypertension in both study years were age, alcohol consumption, overweight and diabetes. A national hypertension control programme should be implemented in order to reduce premature deaths in Myanmar.

Exercise during pregnancy and risk of cesarean delivery in nulliparous women: a large population-based cohort study.

BACKGROUND: Vaginal delivery for the first birth is of great importance for further obstetric performance for the individual woman. Given the rising cesarean delivery rates worldwide over the past decades, a search for modifiable factors that are associated with cesarean delivery is needed. Exercise may be a modifiable factor that is associated with type of delivery, but the results of previous studies are not conclusive. OBJECTIVE: The purpose of this study was to investigate the association between exercise during pregnancy and cesarean delivery, both acute and elective, in nulliparous women. STUDY DESIGN: We conducted a population-based cohort study that involved 39,187 nulliparous women with a singleton pregnancy who were enrolled in the Norwegian Mother and Child Cohort Study between 2000 and 2009. All women answered 2 questionnaires in pregnancy weeks 17 and 30. Acute and elective cesarean delivery data were obtained from the Medical Birth Registry of Norway. Information on exercise frequency and type was assessed prospectively by questionnaires in pregnancy weeks 17 and 30. Generalized linear models estimated risk differences of acute and elective cesarean delivery for different frequencies and types of exercise during pregnancy weeks 17 and 30. We used restricted cubic splines to examine dose-response associations of exercise frequency and acute cesarean delivery. A test for nonlinearity was also conducted. RESULTS: The total cesarean delivery rate was 15.4% (n=6030), of which 77.8% (n=4689) was acute cesarean delivery. Exercise during pregnancy was associated with a reduced risk of cesarean delivery, particularly for acute cesarean delivery. A nonlinear association was observed for exercise frequency in weeks 17 and 30 and risk of acute cesarean delivery (test for nonlinearity, P=.003 and P=.027, respectively). The largest risk reduction was observed for acute cesarean delivery among women who exercised >5 times weekly during weeks 17 (-2.2%) and 30 (-3.6%) compared with nonexercisers (test for trend, P<.001). Reporting high impact exercises in weeks 17 and 30 was associated with the greatest reduction in risk of acute cesarean delivery (-3.0% and -3.4%, respectively). CONCLUSION: Compared with nonexercisers, regular exercise and high-impact exercises during pregnancy are associated with reduced risk of having an acute cesarean delivery in first-time mothers.

Novel application of statistical methods for analysis of multiple toxicants identifies DDT as a risk factor for early child behavioral problems.

BACKGROUND: The aim of this study was to assess the association between postnatal exposure to multiple persistent organic pollutants (POPs) measured in breast milk samples and early behavioral problems using statistical methods to deal with correlated exposure data. METHODS: We used data from the Norwegian HUMIS study. We measured concentrations of 24 different POPs in human milk from 612 mothers (median collection time: 32 days after delivery), including 13 polychlorinated biphenyls (PCB) congeners, 6 polybrominated diphenyl ethers (PBDE) congeners and five organochlorine compounds. We assessed child behavioral problems at 12 and 24 months using the infant toddler symptom checklist (ITSC). Higher score in ITSC corresponds to more behavioral problems. First we performed principal component analysis (PCA). Then two variable selection methods, elastic net (ENET) and Bayesian model averaging (BMA), were applied to select any toxicants associated with behavioral problems. Finally, the effect size of the selected toxicants was estimated using multivariate linear regression analyses. RESULTS: p,p'-DDT was associated with behavioral problems at 12 months in all the applied models. Specifically, the principal component composed of organochlorine pesticides was significantly associated with behavioral problems and both ENET and BMA identified p,p'-DDT as associated with behavioral problems. Using a multiple linear regression model an interquartile increase in p,p'-DDT was associated with a 0.62 unit increase in ITSC score (95% CI 0.45, 0.79) at 12 months, corresponding to more behavioral problems. The association was modified by maternal education: the effect of p,p'-DDT was strongest in women with lower education (ß=0.59; 95%CI: 0.38, 0.81) compared to the mother with higher education (ß=0.14; 95%CI: -0.05, 0.34) (p-value for interaction=0.089). At 24 months, neither selection method consistently identified any toxicant associated with behavioral problems. CONCLUSION: Within a mixture of 24 toxicants measured in breast milk, p,p'-DDT was the single toxicant associated with behavioral problems at 12 months using different methods for handling numerous correlated exposures.

Urban-rural differences in the prevalence of non-communicable diseases risk factors among 25-74 years old citizens in Yangon Region, Myanmar: a cross sectional study.

BACKGROUND: Recent societal and political reforms in Myanmar may upturn the socio-economy and, thus, contribute to the country's health transition. Baseline data on urban-rural disparities in non-communicable disease (NCD) risk factors are not thoroughly described in this country which has been relatively closed for more than five decades. We aim to investigate urban-rural differences in mean values and the prevalence of selected behavioral and metabolic risk factors for non-communicable diseases and 10-years risk in development of coronary heart diseases (CHD). METHODS: Two cross-sectional studies were conducted in urban and rural areas of Yangon Region in 2013 and 2014 respectively, using the WHO STEPwise approach to surveillance of risk factors of NCDs. Through a multi-stage cluster sampling method, 1486 participants were recruited. RESULTS: Age-standardized prevalence of the behavioral risk factors tended to be higher in the rural than urban areas for all included factors and significantly higher for alcohol drinking (19.9% vs. 13.9%; p = 0.040) and low fruit & vegetable consumption (96.7% vs. 85.1%; p = 0.001). For the metabolic risk factors, the tendency was opposite, with higher age-standardized prevalence estimates in urban than rural areas, significantly for overweight and obesity combined (40.9% vs. 31.2%; p = 0.023), obesity (12.3% vs.7.7%; p = 0.019) and diabetes (17.2% vs. 9.2%; p = 0.024). In sub-group analysis by gender, the prevalence of hypercholesterolemia and hypertriglyceridemia were significantly higher in urban than rural areas among males, 61.8% vs. 40.4%; p = 0.002 and 31.4% vs. 20.7%; p = 0.009, respectively. Mean values of age-standardized metabolic parameters showed higher values in urban than rural areas for both male and female. Based on WHO age-standardized Framingham risk scores, 33.0% (95% CI = 31.7-34.4) of urban dwellers and 27.0% (95% CI = 23.5-30.8) of rural dwellers had a moderate to high risk of developing CHD in the next 10 years. CONCLUSION: The metabolic risk factors, as well as a moderate or high ten-year risk of CHD were more common among urban residents whereas behavioral risk factors levels were higher in among the rural people of Yangon Region. The high prevalences of NCD risk factors in both urban and rural areas call for preventive measures to reduce the future risk of NCDs in Myanmar.

Workplace aggression, psychological distress, and job satisfaction among Palestinian nurses: A cross-sectional study.

BACKGROUND: Nurses can be exposed to aggressive behavior from patients, patient's relatives, colleagues and visitors. PURPOSE: To determine the prevalence of workplace aggression among Palestinian nurses in the Hebron district and to examine cross-sectional associations between exposure to workplace aggression and the occurrence of psychological distress and job satisfaction. METHODS: Of 372 nurses eligible for the study, 343 were included (response rate of 92.2%). The sample comprised 62% females and 38% males. The participants responded to questions about their socio-demographic status, workplace aggression (WHO questionnaires), psychological distress (General Health Questionnaire, GHQ-30), and job satisfaction (Generic Job Satisfaction Scale). RESULTS: Ninety-three (27.1%) of the respondents reported exposure to workplace aggression of any kind. Seventeen (5%) reported exposure to physical aggression, 83 (24.2%) reported exposure to verbal aggression, and 25 (7.3%) reported exposure to bullying. The patients and the patients' relatives were the main sources of physical and verbal aggression, whereas colleagues were the main source of bullying. Males reported a higher prevalence of bullying than females. Younger nurses reported a higher prevalence of exposure to physical aggression, verbal aggression and bullying. Verbal aggression was associated with more psychological distress. Bullying was associated with lower job satisfaction. CONCLUSIONS: More than a quarter of the nurses reported that they had been subject to some sort of aggression at the workplace. Verbal aggression was associated with higher psychological distress. Workplace bullying was associated with lower job satisfaction. Increased awareness and preventive measures to address this problem among health care workers are warranted.