Association of Common Medications and the Risk of Early-Onset Gastric Cancer: A Population-Based Matched Study

Background. Early-onset gastric cancer (EOGC, age ≤ 60 years at diagnosis) now comprises >30% of new gastric cancers in the United States. It is hypothesized that chronic acid suppression with proton-pump inhibitors (PPIs) may promote tumorigenesis, while other medications including statins, nonsteroidal anti-inflammatory drugs (NSAIDs), metformin, and cyclooxygenase-2 (COX-2) inhibitors have been proposed as protective. We aimed to assess for an association between use of the aforementioned commonly prescribed medications and EOGC development. Methods. We used a population-based medical record linkage system, to identify cases of EOGC in Olmsted County, Minnesota, between January 1, 1995, and December 31, 2020. Patients were matched 1 : 1 with controls based on age at diagnosis, sex, smoking status, and body mass index (BMI). Conditional logistic regression was used to examine associations with the odds of EOGC development. Results. Ninety-six cases of EOGC were identified during the study period. On both univariate and multivariate regression analysis, there was no significant association between use of PPIs, statins, NSAIDs, or metformin and EOGC development. In a final multivariable model, there was a significant reduction in odds of EOGC with COX-2 inhibitor use for six months or more prior to cancer diagnosis ( OR = 0.39 , 95% CI 0.16-0.94). Conclusion. In this retrospective, population-based study of individuals in Olmsted County, MN, we found significantly reduced odds of EOGC development associated with COX-2 inhibitor use for six months or more prior to diagnosis, but no association between EOGC development and use of PPIs and other commonly prescribed medications.

Epidemiological studies of CT scans and cancer risk: the state of the science

20 years ago, 3 manuscripts describing doses and potential cancer risks from CT scans in children raised awareness of a growing public health problem. We reviewed the epidemiological studies that were initiated in response to these concerns that assessed cancer risks from CT scans using medical record linkage. We evaluated the study methodology and findings and provide recommendations for optimal study design for new efforts. We identified 17 eligible studies; 13 with published risk estimates, and 4 in progress. There was wide variability in the study methodology, however, which made comparison of findings challenging. Key differences included whether the study focused on childhood or adulthood exposure, radiosensitive outcomes (e.g. leukemia, brain tumors) or all cancers, the exposure metrics (e.g. organ doses, effective dose or number of CTs) and control for biases (e.g. latency and exclusion periods and confounding by indication). We were able to compare results for the subset of studies that evaluated leukemia or brain tumors. There were eight studies of leukemia risk in relation to red bone marrow (RBM) dose, effective dose or number of CTs; seven reported a positive dose–response, which was statistically significant (p < 0.05) in four studies. Six of the seven studies of brain tumors also found a positive dose–response and in five, this was statistically significant. Mean RBM dose ranged from 6 to 12 mGy and mean brain dose from 18 to 43 mGy. In a meta-analysis of the studies of childhood exposure the summary ERR/100 mGy was 1.78 (95%CI: 0.01–3.53) for leukemia/myelodisplastic syndrome (n = 5 studies) and 0.80 (95%CI: 0.48–1.12) for brain tumors (n = 4 studies) (p-heterogeneity >0.4). Confounding by cancer pre-disposing conditions was unlikely in these five studies of leukemia. The summary risk estimate for brain tumors could be over estimated, however, due to reverse causation. In conclusion, there is growing evidence from epidemiological data that CT scans can cause cancer. The absolute risks to individual patients are, however, likely to be small. Ongoing large multicenter cohorts and future pooling efforts will provide more precise risk quantification.

POS1338 INCIDENCE, PREVALENCE, AND MORTALITY OF CHRONIC PERIAORTITIS: A POPULATION-BASED STUDY

Background:Chronic periaortitis is an inflammatory condition that typically involves the infrarenal portion of the abdominal aorta. Few studies are available to outline the epidemiology of this rare condition. To date, no epidemiologic studies on periaoritis have been performed in North America.Objectives:To evaluate the epidemiology, presentation and outcomes of patients with chronic periaortitis from 1998 through 2018.Methods:An inception cohort of patients with incident chronic periaortitis from January 1, 1998 through December 31, 2018, in Olmsted County, Minnesota, USA, was identified based on comprehensive individual medical record review utilizing the Rochester Epidemiology Project medical record linkage system. Inclusion required radiographic and/or histologic confirmation of periarterial soft tissue thickening around at least part of the infra-renal abdominal aorta or the common iliac arteries. Data were collected on demographic characteristics, clinical presentation, renal and radiographic outcomes, and mortality. Incidence rates were age and sex adjusted to the 2010 United States white population.Results:Eleven incident cases of chronic periaortitis were identified during the study period. Mean±SD age at diagnosis was 61.8±13.4 years. The cohort included 9 men (82%) and 2 women (18%). The most common presenting symptom was pain with 55% (6/11) reporting abdominopelvic-pelvic pain, 36% (4/11) back pain, and 18% (2/11) flank pain. Obstructive uropathy was present in 73% (8/11) subjects: 3 (27%) unilateral left, 1 (9%) unilateral right, and 4 (36%) bilateral. Mean creatinine at presentation was 2.7±3.4 mg/dL. Ureteral stenting was required at diagnosis in seven patients: unilateral left in 2, unilateral right in 1 and bilateral in 4. All 11 patients received glucocorticoids with a median (IQR) dose of 40 (30, 60) mg/day. Additional non-glucocorticoid therapeutics were used in 10 patients.Renal function stage at last follow up declined in 2 patients, remained the same in 3 patients and improved in 6 patients. Mean creatinine at last follow-up was 1.2±0.2 mg/dL. Among the seven patients requiring baseline indwelling ureteral stent placement only two required ongoing ureteral stenting at last follow up. None of the four patients without ureteral stenting at diagnosis progressed to require stenting during the follow-up period. No patient underwent ureterolysis surgery in this cohort. Periarterial soft tissue thickening at last follow up had increased in thickness in 1 (9%), was unchanged in 2 (18%), decreased in size but did not resolve in 6 (55%), and fully resolved in 18%.Age- and sex-adjusted incidence rates per 100,000 population were 0.26 for females, 1.56 for males and 0.87 overall. Overall prevalence on January 1, 2015 was 8.98 per 100,000 population. Median (IQR) length of follow-up was 10.1 (2.5, 13.8) years. Overall mortality was similar to the expected age, sex, and calendar estimates of the Minnesota population with standardized mortality ratio (95% CI) for the entire cohort 2.07 (0.67, 4.84).Conclusion:This study reports the first epidemiologic data on chronic periaortitis in the United States. In this cohort of patients with chronic periaortitis, men were approximately 4 times more commonly affected than women. Mortality was not increased compared to the general population.Disclosure of Interests:None declared

The Genetic Links to Anxiety and Depression (GLAD) Study: online recruitment into the largest recontactable study of depression and anxiety

BackgroundAnxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety, with broad assessment of risks to facilitate future research.MethodsThe Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact.ResultsOnline recruitment was effective; 41,892 consented and 26,877 participants completed the questionnaire by July 2019. Participants’ questionnaire data identified very high rates recurrent depression, severe anxiety and comorbidity. Participants reported high rates of treatment receipt. The age profile of sample is biased toward young adults, with higher recruitment of females and the better educated, especially at younger ages.DiscussionThis paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes and treatment for anxiety and depression.HighlightsOnline recruitment of 40,000 individuals with lifetime depression or anxiety (77 characters)Detailed online phenotyping combined with genetic and clinical data (66 characters)The study sample is severe, highly comorbid, with chronic psychopathology (62 characters)The study protocol enables recall of participants for future research and trials (82 characters)The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health or King’s College London

Spatio-temporal comparison of pertussis outbreaks in Olmsted County, Minnesota, 2004–2005 and 2012: a population-based study

ObjectiveTwo pertussis outbreaks occurred in Olmsted County, Minnesota, during 2004–2005 and 2012 (5–10 times higher than other years), with significantly higher incidence than for the State. We aimed to assess whether there were similar spatio-temporal patterns between the two outbreaks.SettingOlmsted County, Minnesota, USAParticipantsWe conducted a population-based retrospective cohort study of all Olmsted County residents during the 2004–2005 and 2012 outbreaks, including laboratory-positive pertussis cases.Primary outcome measureFor each outbreak, we estimated (1) age-specific incidence rate using laboratory-positive pertussis cases (numerator) and the Rochester Epidemiology Project Census (denominator), a medical record-linkage system for virtually all Olmsted County residents, and (2) pertussis case density using kernel density estimation to identify areas with high case density. To account for population size, we calculated relative difference of observed density and expected density based on age-specific incidence.ResultsWe identified 157 and 195 geocoded cases in 2004–2005 and 2012, respectively. Incidence was the highest among adolescents (ages 11 to <14 years) for both outbreaks (9.6 and 7.9 per 1000). The 2004–2005 pertussis outbreak had higher incidence in winter (52% of cases) versus summer in 2012 (53%). We identified a consistent area with higher incidence at the beginning (ie, first quartile) of two outbreaks, but it was inconsistent for later quartiles. The relative difference maps for the two outbreaks suggest a greater role of neighbourhood population size in 2012 compared with 2004–2005.ConclusionsComparing spatio-temporal patterns between two pertussis outbreaks identified a consistent geographical area with higher incidence of pertussis at the beginning of outbreaks in this community. This finding can be tested in future outbreaks, and, if confirmed, can be used for identifying epidemiological risk factors clustered in such areas for geographically targeted intervention.

Erectile Dysfunction Preceding Clinically Diagnosed α-Synucleinopathies: A Case-Control Study in Olmsted County

Objective. Autonomic symptoms are common in α-synuclein disorders: multiple system atrophy (MSA), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and Parkinson’s disease with dementia (PDD). These symptoms may precede the motor findings/clinical diagnosis by years. Erectile dysfunction (ED) is an autonomic symptom that has rarely been studied in these α-synuclein disorders. In this population-based, case-control study, we investigated the association between premonitory erectile dysfunction surfacing prior to the clinical-motor manifestations of these α-synucleinopathies. Methods. We used the medical record-linkage system of the Rochester Epidemiology Project to identify cases of α-synucleinopathies in Olmsted County from 1991 to 2010. Each male case was matched by age (±1 year) of symptom onset and sex to a control. We reviewed complete medical records of cases and controls to detect erectile dysfunction prior to the clinical-motor onset of α-synucleinopathies of any type. We used conditional logistic regression to calculate the odds ratio of all α-synucleinopathies, as well as by type, adjusting for diabetes, coffee, and smoking. Results. A history of male erectile dysfunction was associated with 1.5-fold increased odds of an α-synucleinopathy diagnosis of any type in univariate analyses (p=0.06). When stratifying α-synucleinopathies by type, early erectile dysfunction was most frequent in MSA cases than matched controls (45% vs. 9%). Premotor phase ED was next most frequent among the DLB cases (46% vs. 27% among the controls; OR = 2.83, p=0.03; when adjusted for diabetes, smoking, and coffee, OR = 2.98, p=0.04). Premotor phase ED was not significantly associated with PD or PDD. Conclusions. Early erectile dysfunction may be a premotor symptom of MSA and DLB, reflecting premonitory dysautonomia. It was not associated with premotor PD or PDD.

Abstract 17019: Secular Trends in Dilated and Hypertrophic Cardiomyopathy in an Epidemiological Cohort in Olmsted County, Minnesota

Introduction: Idiopathic Dilated (DCM) and hypertrophic cardiomyopathies (HCM) are leading causes of sudden cardiac death. The incidence and prevalence of both DCM and HCM were originally estimated in Olmsted County, MN over 1975-1984. Incidence was 6.0 and prevalence was 36.5 per 100,000 person-years, for DCM; with incidence and prevalence rates of 2.5 and 19.7 per 100,000 person-years for HCM. This study aims to determine the incidence and mortality rates of individuals diagnosed with HCM and DCM in Olmsted County, MN from 1984 to 2016. Methods: The Rochester Epidemiology Project is a validated long term medical record linkage system that collects and links medical information for the approximately 145000 residents of Olmsted County, Minnesota. Using this database and the Electronic Health Record systems at Mayo Clinic and Olmsted Medical Center in Rochester, MN, we manually reviewed and validated the medical records of 4440 patients. This cohort includes all patients with any mention of a cardiomyopathy based on ICD and HICDA codes during the period 1984 to 2016. Data were summarized with mean and standard deviation, frequency and percentage and compared between groups using two sample t-test for continuous data and chi-square for proportions. Survival was computed using Kaplan-Meier methods and compared to expected survival based on age and gender. Incidence was computed using Olmsted County population numbers during the time period and adjusted to the US 1980 white population to allow for comparison with the previous study. Results: The calculated crude incidence rate for DCM and HCM are 10.1 and 7.8 per 100,000 respectively. Incidence rates adjusted for comparison to US 1980 white population (age and sex adjusted) are 10.4 (95% CI: 9.3-11.4) and 8.0 (95% CI: 7.1-8.8) per 100,000 person-years, respectively. The observed number of deaths in this cohort (HCM and DCM) was 420 vs 194 expected. Conclusions: Calculated incidence, both crude and adjusted rates are higher than previously estimated rates. The crude incidence rate for HCM is almost 4-fold higher than that for DCM is 2.4 times higher than the original estimate by Codd et al. Individuals with cardiomyopathies were found to have a higher overall mortality rate than the general population with an observed to expected hazard ratio of 1.73 (95% CI 1.49-2.01, p<0.001) for DCM and 1.44 (95% CI 1.21-1.71, p<0.001) for HCM. Our findings suggest that previous studies may have underestimated the true burden of HCM and DCM in the population which has important implications for healthcare provision and cost.

Long-term weight loss following a randomised controlled trial of a weight management programme for men delivered through professional football clubs: the Football Fans in Training follow-up study

Background Rising levels of obesity require interventions that support people in long-term weight loss. The Football Fans in Training (FFIT) programme uses loyalty to football teams to engage men in weight loss. In 2011/12, a randomised controlled trial (RCT) found that the FFIT programme was effective in helping men lose weight up to 12 months. Objectives To investigate the long-term weight, and other physical, behavioural and psychological outcomes up to 3.5 years after the start of the RCT; the predictors, mediators and men’s qualitative experiences of long-term weight loss; cost-effectiveness; and the potential for long-term follow-up via men’s medical records. Design A mixed-methods, longitudinal cohort study. Setting Thirteen professional Scottish football clubs from the RCT and 16 additional Scottish football clubs that delivered the FFIT programme in 2015/16. Participants A total of 665 men who were aged 35–65 years at the RCT baseline measures and who consented to follow-up after the RCT (intervention group, n = 316; comparison group, n = 349), and 511 men who took part in the 2015/16 deliveries of the FFIT programme. Interventions None as part of this study. Main outcome measures Objectively measured weight change from the RCT baseline to 3.5 years. Results In total, 488 out of 665 men (73.4%) attended 3.5-year measurements. Participants in the FFIT follow-up intervention group sustained a mean weight loss from baseline of 2.90 kg [95% confidence interval (CI) 1.78 to 4.02 kg; p < 0.001], and 32.2% (75/233) weighed ≥ 5% less than at baseline. Participants in the FFIT follow-up comparison group (who participated in routine deliveries of the FFIT programme after the RCT) lost a mean of 2.71 kg (95% CI 1.65 to 3.77 kg; p < 0.001), and 31.8% (81/255) achieved ≥ 5% weight loss. Both groups showed long-term improvements in body mass index, waist circumference, percentage body fat, blood pressure, self-reported physical activity (PA) (including walking), the consumption of fatty and sugary foods, fruit and vegetables and alcohol, portion sizes, self-esteem, positive and negative affect, and physical and mental health-related quality of life (HRQoL). Mediators included self-reported PA (including walking) and sitting time, the consumption of fatty and sugary foods and fruit and vegetables, portion sizes, self-esteem, positive affect, physical HRQoL, self-monitoring of weight, autonomous regulation, internal locus of control, perceived competence, and relatedness to other FFIT programme participants and family members. In qualitative interviews, men described continuing to self-monitor weight and PA. Many felt that PA was important for weight control, and walking remained popular; most were still aware of portion sizes and tried to eat fewer snacks. The FFIT programme was associated with an incremental cost-effectiveness of £10,700–15,300 per quality-adjusted life-year (QALY) gained at 3.5 years, and around £2000 per QALY gained in the lifetime analysis. Medical record linkage provided rich information about the clinical health outcomes of the FFIT RCT participants, and 90% of men (459/511) who took part in the 2015/16 FFIT programme gave permission for future linkage. Conclusions Participation in the FFIT programme under both research (during the FFIT RCT) and routine (after the FFIT RCT) delivery conditions led to significant long-term weight loss. Further research should investigate (1) how to design programmes to improve long-term weight loss maintenance, (2) longer-term follow-up of FFIT RCT participants and (3) very long-term follow-up via medical record linkage. Trial registration Current Controlled Trials ISRCTN32677491. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 6, No. 9. See the NIHR Journals Library website for further project information. The Scottish Executive Health Department Chief Scientist Office (CSO) funded the feasibility pilot that preceded the FFIT RCT (CZG/2/504). The Medical Research Council (MRC) funded Kate Hunt and additional developmental research through the MRC/CSO Social and Public Health Sciences Unit Gender and Health programme (5TK50/25605200-68094).

Population-based incidence of conjunctival tumours in Olmsted County, Minnesota

AimTo determine population-based incidence of conjunctival tumours in Olmsted County, Minnesota.MethodsThe Rochester Epidemiology Project medical record linkage system was used to identify patients with conjunctival tumours in Olmsted County (1 January 1980 to 31 December 2015). Records were reviewed for demographics, types of tumours, histopathology, treatment and clinical course. Incidence rate of all tumours was calculated per 1 000 000 person-years. Poisson regression analysis was used to assess changes in incidence over time.ResultsThere were 504 patients with conjunctival tumours, giving an age-adjusted and sex-adjusted incidence rate of 125 per 1 000 000 (CI 113.5 to 135.5). Incidence increased over time (P<0.001). Most tumours (474, 94%) were benign. Of benign lesions, melanocytic lesions accounted for the majority (431, 86%), with adjusted incidence rates of 10.8 (CI 7.7 to 13.9) for complexion-associated melanosis, 49.7 (CI 42.9 to 56.6) for nevus and 44.1 (37.5–50.8) for primary acquired melanosis. Malignant lesions were rare (30, 6%) with 6 cases of melanoma, 21 cases of ocular surface squamous neoplasia (OSSN), 1 case of Langerhans cell histiocytosis and 2 cases of lymphoma. Adjusted incidence rates of conjunctival melanoma and OSSN were 1.5 (CI 0.3 to 2.8) and 6.1 (CI 3.5 to 8.7), respectively. Outcomes for melanoma (mean follow-up 14 years, range 0–34) and OSSN (mean follow-up 4 years, range 0–24) were favourable in 29 cases, with one fatality due to metastatic melanoma.ConclusionsIn a population-based setting, most conjunctival tumours are benign, and the majority of lesions are melanocytic. While it is important to remain vigilant for malignancies, most conjunctival lesions in a community-based practice are not life-threatening.