Patients With Stricturing or Penetrating Crohn's Disease Phenotypes Report High Disease Burden and Treatment Needs.

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited. METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference. RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), stricturing CD (n = 457, 29.4%), penetrating CD (n = 166, 10.7%), and CD-SP (n = 260, 16.7%). Patients with complicated phenotypes reported significantly greater use of tumor necrosis factor inhibitors (84.2%-86.7% vs 66.0%; P < .001) and corticosteroids (75.3%-82.7% vs 68.0%; P < .001). Patients with CD-SP reported significantly more aphthous ulcer (15.4% vs 10.5%; P < .05), erythema nodosum (6.5% vs 3.6%; P < .05), inflammatory bowel disease-related arthropathy (25.8% vs 17.2%; P < .01), liquid stools (24.2% vs 9.3%; P < .001), nocturnal fecal incontinence (10.8% vs 2.5%; P < .001), and CD-related surgery (77.7% vs 12.2%; P < .001). CONCLUSIONS: Patients with complicated CD phenotypes reported higher rates of active CD-related luminal and extraintestinal manifestations, and underwent more surgeries, despite being more likely to have received biologics than those with CD-I. The potential for early recognition and management of CD-I to prevent progression to complicated phenotypes should be explored in longitudinal studies.

Patients with complicated (stricturing and/or penetrating) Crohn's disease (CD) phenotypes have a higher disease burden, despite greater use of biologics, than patients with inflammatory CD. Early recognition and optimized management of CD may prevent progression to complicated phenotypes.

Thyroid Cancer and Pesticide Use in a Central California Agricultural Area: A Case Control Study.

OBJECTIVE: To examine environmental factors that influence risk of thyroid cancer. METHODS: We performed a case-control study utilizing thyroid cancer cases from the California Cancer Registry (1999-2012) and controls sampled in a population-based manner. Study participants were included if they were diagnosed with thyroid cancer, lived in the study area at their time of diagnosis, and were ≥35 years of age. Controls were recruited from the same area and eligible to participate if they were ≥35 years of age and had been living in California for at least 5 years prior to the interview. We examined residential exposure to 29 agricultural use pesticides, known to cause DNA damage in vitro or are known endocrine disruptors. We employed a validated geographic information system-based system to generate exposure estimates for each participant. RESULTS: Our sample included 2067 cases and 1003 controls. In single pollutant models and within a 20-year exposure period, 10 out of 29 selected pesticides were associated with thyroid cancer, including several of the most applied pesticides in the United States such as paraquat dichloride [odds ratio (OR): 1.46 (95% CI: 1.23, 1.73)], glyphosate [OR: 1.33 (95% CI: 1.12, 1.58)], and oxyfluorfen [OR: 1.21 (95% CI: 1.02, 1.43)]. Risk of thyroid cancer increased proportionately to the total number of pesticides subjects were exposed to 20 years before diagnosis or interview. In all models, paraquat dichloride was associated with thyroid cancer. CONCLUSIONS: Our study provides first evidence in support of the hypothesis that residential pesticide exposure from agricultural applications is associated with an increased risk of thyroid cancer.

Parental Occupation and Risk of Childhood Retinoblastoma in Denmark.

OBJECTIVE: Retinoblastoma is the most common primary intraocular tumor affecting children. We examine the role of parental occupational exposures and risk of retinoblastoma among offspring. METHODS: Our population-based case-control study linked data from four nationwide Danish registries and included all cases of retinoblastoma diagnosed in Danish children (<5 y, n = 144) between 1975 and 2014. We focused on two biologically relevant time periods: 90 days preconception to conception for fathers; conception to birth for mothers. Parents were grouped into major industry headings created from Danish industry codes. RESULTS: We observed increased risk of all retinoblastoma for children of fathers in the food and drink industry and iron and metal industry. Bilateral disease was associated with paternal work in manufacturing and land transportation. CONCLUSION: Our results suggest that some occupational exposures may increase the risk of childhood sporadic retinoblastoma.

High parental occupational social contact and risk of childhood hematopoietic, brain and bone cancers.

BACKGROUND: The etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers. METHODS: We examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973-2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis. RESULTS: Acute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67-1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34-0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03-2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02-2.32; paternal: OR: 1.82, 95% CI: 1.05-3.17). CONCLUSION: Our results support the notion of a role of infections for some cancer types.

Improving health with programmatic, legal, and policy approaches to reduce gender inequality and change restrictive gender norms.

Evidence that gender inequalities and restrictive norms adversely affect health is extensive; however, far less research has focused on testing solutions. We first comprehensively reviewed the peer-reviewed and grey literature for rigorously evaluated programmes that aimed to reduce gender inequality and restrictive gender norms and improve health. We identified four mutually reinforcing factors underpinning change: (1) multisectoral action, (2) multilevel, multistakeholder involvement, (3) diversified programming, and (4) social participation and empowerment. Following this review, because little research has investigated the effects of national-level law and policy reforms, we conducted original quasi-experimental studies on laws and policies related to education, work, and income, all social determinants of health in which deep gender inequalities exist. We examined whether the laws and policies significantly affected health outcomes and gender norms, and whether law-induced and policy-induced changes in gender norms mediated the health effects, in areas for which longitudinal data existed. Laws and policies that made primary education tuition-free (13 intervention countries with the law and/or policy and ten control countries without) and that provided paid maternity and parental leave (seven intervention and 15 control countries) significantly improved women's and their children's health (odds ratios [OR] of 1·16-2·10, depending on health outcome) and gender equality in household decision making (OR 1·46 for tuition-free and 1·45 for paid maternity and parental leave) as a proxy indicator of gender norms. Increased equality partially mediated the positive effects on health outcomes. We conclude by discussing examples of how improved governance can support gender-equitable laws, policies, and programmes, immediate next steps, and future research needs.

Parental occupational exposures and the risk of childhood sporadic retinoblastoma: a report from the Children's Oncology Group.

OBJECTIVES: We examined associations between parental occupational chemical exposures up to 10 years before conception and the risk of sporadic retinoblastoma among offspring. METHODS: In our multicentre study on non-familial retinoblastoma, parents of 187 unilateral and 95 bilateral cases and 155 friend controls were interviewed by telephone. Exposure information was collected retroactively through a detailed occupational questionnaire that asked fathers to report every job held in the 10 years before conception, and mothers 1 month before and during the index pregnancy. An industrial hygienist reviewed all occupational data and assigned an overall exposure score to each job indicating the presence of nine hazardous agents. RESULTS: We estimated elevated ORs for unilateral and bilateral retinoblastoma among offspring of fathers who were exposed to polycyclic aromatic hydrocarbons or paints in the 10 years before conception. However, only for exposure to paints did confidence limits exclude the null for bilateral disease (OR: 8.76, 95% CI: 1.32 to 58.09). Maternal prenatal exposure to at least one of the nine agents was related to increased risk of unilateral disease in their children (OR: 5.25, 95% CI: 1.14 to 24.16). Fathers exposed to at least one of the nine agents and who were ≥30 years of age were at increased risk of having a child diagnosed with bilateral retinoblastoma (OR: 6.59, 95% CI: 1.34 to 32.42). CONCLUSIONS: Our results suggest a role for several hazardous occupational exposures in the development of childhood retinoblastoma.

Residential Pesticide Exposures in Pregnancy and the Risk of Sporadic Retinoblastoma: A Report From the Children's Oncology Group.

PURPOSE: To examine whether parental pesticide exposure contributes to the development of sporadic retinoblastoma. DESIGN: Case-control study. METHODS: Data were collected by a large multicenter study of sporadic retinoblastoma in which parents of 99 unilateral and 56 bilateral age-matched case-control pairs were interviewed by telephone. Retrospective exposure information was collected on the type, location, timing, and frequency of residential pesticide use. We used conditional logistic regression analyses to estimate odds ratios for maternal pesticide exposure in the month before or during pregnancy and to assess whether the type of product, and the circumstances under which it was applied, were associated with risk of disease. RESULTS: Unilateral retinoblastoma was associated with parental insecticide use (odds ratio [OR], 2.8; confidence interval [CI], 1.1-6.7) and the use of professional lawn or landscape services (OR, 2.8; CI, 1.0-8.2). For bilateral disease we observed large point estimates for several exposures but the small number of cases rendered these results uninformative (ie, resulted in wide confidence intervals). Whether parents used the pesticide inside vs outside the home did not appear to modify risk estimates for unilateral retinoblastoma (OR, 2.5; CI, 0.9-7.0 vs OR, 2.5; CI, 1.0-6.5), nor did the type, frequency, timing related to pregnancy, or applicator of pesticide used influence estimates to an appreciable degree for disease. CONCLUSIONS: Our results suggest that parental pesticide exposure before or during pregnancy may play a role in the development of childhood retinoblastoma. Retrospectively collected exposure data introduces the possibility of recall bias; therefore, results should be interpreted cautiously until additional studies are conducted.

A case-control study of sporadic retinoblastoma in relation to maternal health conditions and reproductive factors: a report from the Children's Oncology group.

BACKGROUND: The early age at retinoblastoma occurrence, the most common eye malignancy in childhood, suggests that perinatal factors may contribute to its etiology. METHODS: In a large multicenter study of non-familial retinoblastoma, we conducted structured interviews with the parents of 280 cases and 146 controls to elicit information on health during the perinatal period. We used unconditional logistic regression to assess associations between retinoblastoma and parental fertility treatment, birth control use in the year prior to pregnancy, maternal health conditions and the use of prescription medications during pregnancy, and whether mothers breastfed the index child. RESULTS: Bilateral retinoblastoma was related to maternal underweight (body mass index <18.5) prior to pregnancy [Odds Ratio (OR) = 4.5, 95 % confidence interval (CI) 1.0, 20]. With regards to unilateral retinoblastoma, we observed a negative association with the use of condoms in the year prior to pregnancy (OR = 0.4, CI 0.2, 0.9), and a trend towards a positive association with maternal diabetes (OR = 2.2, CI 0.8, 6.6). CONCLUSIONS: Results from our study suggest a role for several maternal health and reproductive factors. Given that there are few epidemiologic studies of retinoblastoma, our results require replication in studies which utilize medical record review.