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Introduction: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with no known cure. Management of IBD is complex and requires those with IBD to have lifelong interactions with the healthcare system. Individuals with IBD who live in rural areas are at risk of poorer health outcomes due to their limited access to care. This study examined healthcare utilization and access to care for rural adults with IBD. The research questions explored in this study were: What are the care experiences of healthcare providers (HCPs) and persons living with IBD in rural areas? What are the enablers and barriers to optimal IBD care in rural environments? What strategies are necessary to enhance care delivery for these individuals with IBD? Methods: This patient-oriented research initiative involved patient and family advisors as active and equal team members in decision-making throughout the project. This article reports on the qualitative findings of a larger mixed-methods study. The setting was one western Canadian province. Fourteen individuals with IBD living in rural areas and three HCPs working in rural areas participated. Interview data were analyzed using thematic analysis. Results: Three themes were identified: communication, stressors and support systems, and coordination of care. Communication with and between HCPs was challenging due to the distance to access care. Participants described challenges related to rural HCPs' lack of IBD-related knowledge. Virtual communication, such as telehealth and phone clinics, was infrequently used yet highly recommended by participants. Individuals with IBD described various stressors and feelings of isolation while living in rural environments, and both participant groups described the need for additional formal and informal support systems to ease these stressors. Coordination of care was considered essential to optimal health outcomes, but individuals frequently experienced gaps in care. Lack of local services such as outpatient clinics, hospitals, laboratory testing, infusion clinics, and pharmacies meant individuals with IBD frequently had to travel to access care. Some participants reported bypassing existing local services, instead preferring the expedited, specialist care within larger centers. Conclusion: Most participants described challenges associated with living in rural areas and suggested health system improvements. Access to multidisciplinary care teams, including IBD physicians and nurses, psychologists, and dieticians, for individuals in rural areas is encouraged, as is the use of virtual care delivery options such as telehealth, online clinics, telephone clinics or advice lines, web-based video-conferencing, and email communication to increase access to care. Continued efforts to recruit and retain rural HCPs with knowledge of IBD are deemed necessary to provide continuity of care within rural environments. Strengthening formal and informal support systems and enhancing psychosocial supports in rural communities are warranted to ensure optimal wellbeing. Online strategies to provide individual and group education related to IBD are strongly recommended. Facilitating access to care in rural areas can increase disease remission, decrease direct and indirect care costs, and promote quality of life in individuals with IBD.

Background: In 2019, cancer patients comprised over 65% of all individuals who requested and received Medical Assistance in Dying (MAID) in Canada. This descriptive study sought to understand the self-reported symptom burden and complexity of cancer patients in the 12 months prior to receiving MAID in Alberta. Methods: Between July 2017 and January 2019, 337 cancer patients received MAID in Alberta. Patient characteristics were descriptively analyzed. As such, 193 patients (57.3%) completed at least one routine symptom-reporting questionnaire in their last year of life. Mixed effects models and generalized estimating equations were utilized to examine the trajectories of individual symptoms and overall symptom complexity within the cohort over this time. Results: The results revealed that all nine self-reported symptoms, and the overall symptom complexity of the cohort, increased as patients’ MAID provision date approached, particularly in the last 3 months of life. While less than 20% of patients experienced high symptom complexity 12 months prior to MAID, this increased to 60% in the month of MAID provision. Conclusions: Cancer patients in this cohort experienced increased symptom burden and complexity leading up to their death. These findings could serve as a flag to clinicians to closely monitor advanced cancer patients’ symptoms, and provide appropriate support and interventions as needed.

Background: Childhood cancer survivors are at increased risk of therapy-related premature menopause (PM), with a cumulative incidence of 8.0%, but the contribution of genetic factors is unknown.Methods: Genome-wide association analyses were conducted to identify single nucleotide polymorphisms (SNPs) associated with clinically diagnosed PM (menopause < 40 years) among 799 female survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study (SJLIFE). Analyses were adjusted for cyclophosphamide equivalent dose of alkylating agents and ovarian radiotherapy (RT) dose (all P values two-sided). Replication was performed using self-reported PM in 1624 survivors participating in the Childhood Cancer Survivor Study (CCSS).Results: PM was clinically diagnosed in 30 (3.8%) SJLIFE participants. Thirteen SNPs (70 kb region of chromosome 4q32.1) upstream of the Neuropeptide Receptor 2 gene (NPY2R) were associated with PM prevalence (minimum P = 3.3 × 10-7 for rs9999820, all P < 10-5). Being a homozygous carrier of a haplotype formed by four of the 13 SNPs (seen in one in seven in the general population but more than 50% of SJLIFE clinically diagnosed PM) was associated with markedly elevated PM prevalence among survivors exposed to ovarian RT (odds ratio [OR] = 25.89, 95% confidence interval [CI] = 6.18 to 138.31, P = 8.2 × 10-6); this finding was replicated in an independent second cohort of CCSS in spite of its use of self-reported PM (OR = 3.97, 95% CI = 1.67 to 9.41, P = .002). Evidence from bioinformatics data suggests that the haplotype alters the regulation of NPY2R transcription, possibly affecting PM risk through neuroendocrine pathways.Conclusions: The haplotype captures the majority of clinically diagnosed PM cases and, with further validation, may have clinical application in identifying the highest-risk survivors for PM for possible intervention by cryopreservation. [ABSTRACT FROM AUTHOR]

Background Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true' incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Methods Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. Results MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. Conclusions When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence. [ABSTRACT FROM AUTHOR]

Background The recent outbreak of Q fever in the Netherlands between 2007 and 2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may cause Q fever but the size of the population exposed during the outbreak remained uncertain as little is known of the infectivity of this pathogen. The quantification of the infectiousness and the corresponding response is necessary for assessing the risk to the population. Methods A human challenge study was published in the 1950s but this study quantified the dose of C. burnetii in relative units. Data from a concurrent guinea pig challenge study were combined with a recent study in which guinea pigs were challenged with a similar aerosol route to quantify human exposure. Concentration estimates for C. burnetii are made jointly with estimates of the dose response parameters in a hierarchical Bayesian framework. Results The dose for 50% infection (InfD50%) in human subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for 50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The probability of a single viable C. burnetii causing infection in humans is 0.44 (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55). Conclusions To our knowledge this is the first human dose-response model for C. burnetii. The estimated dose response relation demonstrates high infectivity in humans. In many published papers the proportion of infected individuals developing illness is reported to be 40%. Our model shows that the proportion of symptomatic infections may vary with the exposure dose. This implies that presence of these bacteria in the environment, even in small numbers, poses a serious health risk to the population. [ABSTRACT FROM AUTHOR]

Survivors of childhood cancer (SCCs) are at increased risk of late effects, which are cancer- and treatment-related side-effects that are experienced months to years post-treatment and encapsulate a range of physical, cognitive and emotional problems including secondary malignancies. Perceived health can serve as an indicator of overall health. This study aims to (1) understand how a patient reported outcome (PRO) of perceived health of SCCs compares to controls who have not had a cancer diagnosis and (2) examine the relationships between perceived health and demographic and clinical variables, and health behavior. A total of 209 SCCs (n = 113 (54.10%) males; median age at diagnosis = 6.50 years; median time off treatment = 11.10 years; mean age at study = 19.00 years) were included. SCCs completed annual assessments as part of Long-Term Survivor Clinic appointments, including a question on perceived health answered on a five-point Likert scale. Data were collected retrospectively from medical charts. Perceived health of SCCs was compared to a control group (n = 836) using data from the 2014 Canadian Community Health Survey. Most SCCs (67%) reported excellent or very good health. The mean perceived health of SCCs (2.15 ± 0.91) was not statistically different from population controls (2.10 ± 0.87). Pain (B = 0.35; p < 0.001), physical activity (B = −0.39; p = 0.013) and concerns related to health resources (B = 0.59; p = 0.002) were significant predictors of perceived health. Factors shown to influence SCCs’ perceived health may inform interventions. Exploration into how SCCs develop their conception of health may be warranted.

Literature exploring the health-related quality of life and care experiences of older adults with inflammatory bowel disease is limited despite the increasing prevalence in this population. The purpose of this study was to explore the perceived health-related quality of life and care experiences in older adults with inflammatory bowel disease in Canada. This study used a mixed-methods convergent design consisting of a descriptive, cross-sectional survey and qualitative descriptive interviews. Fifty-eight participants completed the survey and 24 participants completed interviews. Older adults reported satisfaction with inflammatory bowel disease-related care, high levels of disease control, moderate health-related quality of life, and low levels of patient-healthcare team interactions. Themes identified were (1) Experiences of inflammatory bowel disease in daily life; (2) Accessibility of inflammatory bowel disease-related health services; and (3) Communication and relationships to facilitate inflammatory bowel disease care. Ultimately, quality inflammatory bowel disease care for older adults is contingent upon communication between patients and providers, access to multidisciplinary clinics, and support networks. By ensuring these factors are present, providers and patients can work together collectively toward positive patient outcomes, enhanced satisfaction with care, and greater perceived quality of care., Competing Interests: N.R., B.C., S.P., K.P.K., B.R., and N.T. declare no conflict of interest. U.C. has received honoraria from AbbVie, Tekada, Pfizer, Fresenius Kabi, and Amgen for consultation for advisory board., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Gastroenterology Nurses and Associates.)

The prevalence of inflammatory bowel disease is rising in persons older than 65 years. Although there is extensive literature on inflammatory bowel disease in older adults from a disease-related outcome, epidemiological, and treatment perspective, the older adult perspective on inflammatory bowel disease-related care needs and experiences is not well represented. This scoping review examines the existing literature regarding the care experiences of older adults living with inflammatory bowel disease. A systematic search was conducted using 3 concepts: older adults, inflammatory bowel disease, and patient experience. Seven publications met the inclusion criteria. Reported data include study design and methods, sample characteristics, and findings relevant to the research question. Two themes were identified: preferences for interactions with healthcare personnel and peer support networks, and barriers to accessing care for inflammatory bowel disease needs. An overarching concept across all studies was the need and request for individualized, patient-centered care where patient preferences are considered. This review highlights the need for more research on the older adult age group to guide evidence-informed practice that meets their individual inflammatory bowel disease care needs., Competing Interests: Conflicts of Interest: None to declare., (Copyright © 2023 Society of Gastroenterology Nurses and Associates.)

Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs., Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort ( n = 743; age (years): median 25.8, interquartile range (IQR) 22.1-30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort ( n = 391; age (years): median 31.3, IQR 26.6-37.4)., Results: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): -0.706 (-1.11--0.298), p -value = 7 × 10 -4 ) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126-0.928), p -value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m 2 CED., Conclusions: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatment-related risk of infertility and fertility preservation options.

Study Question: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?, Summary Answer: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy., What Is Known Already: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability., Study Design, Size, Duration: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391)., Participants/materials, Setting, Methods: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis., Main Results and the Role of Chance: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00)., Limitations, Reasons for Caution: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function., Wider Implications of the Findings: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer., Study Funding/competing Interest(s): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure. Results Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors. Conclusion The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.

Context: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited., Objective: To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes., Design: Cross-sectional., Setting: The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center., Patients: Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis., Main Outcome Measure: POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED)., Results: The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI., Conclusion: High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes., (Copyright © 2017 Endocrine Society)