Factors associated with non-participation in cervical cancer screening - A nationwide study of nearly half a million women in Denmark.

Cervical cancer occurs most often in under-screened women. In this nationwide register study, we described differences in sociodemographic characteristics between passive and active non-participants and examined socio-demographic characteristics, reproductive history, and mental and physical health as potential determinants for passive non-participation compared with participation in the Danish cervical cancer screening program. Screening history in women aged 23-49 years invited for cervical cancer screening in 2008-2009 was retrieved from the Danish Pathology Databank with information about dates of invitation and unsubscription. We identified participants (n = 402,984), active non-participants (n = 10,251) and passive non-participants (n = 63,435) within four years following baseline invitation and retrieved data about the study population from high-quality registries. We examined differences in socio-demographic characteristics of passive and active non-participants, and used multiple logistic regression analyses to identify potential determinants of passive non-participation. We found that active and passive non-participants differed in relation to socio-demography. When compared with screening participants, the odds of passive non-participation was increased in women who originated from less developed countries; were unmarried; had basic education or low income; had four or more children; smoked during pregnancy; had multiple induced abortions; or had a history of obesity, intoxicant abuse or schizophrenia or other psychoses. In conclusion, in this nationwide, prospective, population-based study, differences in socio-demographic characteristics between passive and active non-participants were found. Furthermore, sociodemography, reproductive history, and mental and physical health were determinants for passive non-participation. Addressing inequalities in screening attendance may help to further decrease the incidence of and mortality from cervical cancer.

Mediation analysis for logistic regression with interactions: Application of a surrogate marker in ophthalmology.

Mediation analysis is often based on fitting two models, one including and another excluding a potential mediator, and subsequently quantify the mediated effects by combining parameter estimates from these two models. Standard errors of such derived parameters may be approximated using the delta method. For a study evaluating a treatment effect on visual acuity, a binary outcome, we demonstrate how mediation analysis may conveniently be carried out by means of marginally fitted logistic regression models in combination with the delta method. Several metrics of mediation are estimated and results are compared to findings using existing methods.

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies.

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.

The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: A pooled analysis of 18 case-control studies.

PURPOSE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated. METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model. RESULTS: Overall, women who completed ≤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking. CONCLUSION: Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay.

GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness.

The incretin hormones glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from intestinal endocrine cells, the so-called L- and K-cells. The cells are derived from a common precursor and are highly related, and co-expression of the two hormones in so-called L/K-cells has been reported. To investigate the relationship between the GLP1- and GIP-producing cells more closely, we generated a transgenic mouse model expressing a fluorescent marker in GIP-positive cells. In combination with a mouse strain with fluorescent GLP1 cells, we were able to estimate the overlap between the two cell types. Furthermore, we used primary cultured intestinal cells and isolated perfused mouse intestine to measure the secretion of GIP and GLP1 in response to different stimuli. Overlapping GLP1 and GIP cells were rare (∼5%). KCl, glucose and forskolin+IBMX increased the secretion of both GLP1 and GIP, whereas bombesin/neuromedin C only stimulated GLP1 secretion. Expression analysis showed high expression of the bombesin 2 receptor in GLP1 positive cells, but no expression in GIP-positive cells. These data indicate both expressional and functional differences between the GLP1-producing 'L-cell' and the GIP-producing 'K-cell'.

Factors associated with type-specific persistence of high-risk human papillomavirus infection: A population-based study.

Persistent genital infection with high-risk (HR) human papillomavirus (HPV) is a prerequisite for cervical cancer development. The aim of this study was to identify factors associated with type-specific persistence of HR HPV infections. From a population-based cohort of 40,399 women participating in cervical cancer screening established during 2002-2005, we selected all HR HPV-positive women (N = 7,778). During follow-up (2005-2008), we collected cervical samples from these women and tested them for HPV DNA to determine type-specific HR HPV persistence in the interval 1-4.5 years after enrolment. Data on hospitalisations, prescriptions and socioeconomic factors were obtained from nationwide registers. Women with abnormal cytology at baseline or who had undergone conisation during follow-up were excluded. Factors associated with persistence were identified by logistic regression analysis. The overall rate of HR HPV persistence was 31.4%. The risk for persistence was significantly increased among women with a previous episode of genital warts (OR, 1.35; 95% CI, 1.04-1.74), current use of oral contraceptives (OR, 1.35; 95% CI, 1.13-1.63) or use of systemic glucocorticoids (OR, 2.04; 95% CI, 1.16-3.56). The number of pregnancies or births or use of a hormonal intrauterine device, hormonal therapy or nonsteroidal anti-inflammatory drugs was not associated with risk for HR HPV persistence. A history of genital warts and current use of oral contraceptives or systemic glucocorticoids increased the risk, potentially indicating a decreased immune response to HPV infection. These findings suggest that host immune response characteristics are important in HR HPV persistence and consequently in cervical cancer development.

Interaction between asthma and lung function growth in early life.

RATIONALE: The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma. OBJECTIVES: To analyze the interaction between lung function development and asthma from birth to 7 years of age. METHODS: The Copenhagen Prospective Studies on Asthma in Childhood is a prospective clinical study of a birth cohort of 411 at-risk children. Spirometry was completed in 403 (98%) neonates and again by age 7 in 317 children (77%). MEASUREMENTS AND MAIN RESULTS: Neonatal spirometry and bronchial responsiveness to methacholine was measured during sedation by forced flow-volume measurements. Asthma was diagnosed prospectively from daily diary cards and clinic visits every 6 months. Children with asthma by age 7 (14%) already had a significant airflow deficit as neonates (forced expiratory flow at 50% of vital capacity second in neonates reduced by 0.34 z score by 1 mo; P = 0.03). This deficit progressed significantly during early childhood (forced expiratory flow at 0.5 seconds in neonates at age 7 reduced by 0.82 z score by age 7; P < 0.0001), suggesting that approximately 40% of the airflow deficit associated with asthma is present at birth, whereas 60% develops with clinical disease. Environmental tobacco exposure, but not allergic sensitization, also hampered airflow growth. Bronchial responsiveness to methacholine in the neonates was associated with the development of asthma (P = 0.01). CONCLUSIONS: Children developing asthma by age 7 had a lung function deficit and increased bronchial responsiveness as neonates. This lung function deficit progressed to age 7. Therefore, research into the origins and prevention of asthma should consider early life before and after birth.