Hypertensive disorders of pregnancy and risk of Alzheimer’s disease, vascular dementia, and other related dementia

Several recent studies have examined whether hypertensive disorders of pregnancy (HDP) are associated with an increased risk for Alzheimer’s disease (AD) and other related dementias (RD) with conflicting findings. Limitations to prior studies include lack of assessing risk by dementia subtype, inadequate sample sizes, and not fully exploring the role of mid-life factors. We performed a retrospective matched cohort study among women with >1 singleton pregnancy (1939–2013) using the Utah Population Database. HDP-exposed women (n=19,989) were one-to-two matched with unexposed women (n=39,679) by 5-year age groups, year of childbirth (within 1 year), and parity (1, 2, 3, 4, ≥5) at the time of the pregnancy. HDP pregnancies were complicated by preeclampsia (62%), gestational hypertension (34%), and eclampsia (4%). Women with a history of HDP had a higher hazard of all-cause dementia (HR=1.37; 95% CI: 1.26, 1.50) compared to women without a history of HDP after adjustment for maternal age, year of childbirth, and parity. The hazard doubled after additionally accounting for pre-pregnancy BMI (HR=2.31; 95% CI: 1.24, 4.32). Stratifying by dementia subtype, we found HDP to be associated with a higher hazard of vascular dementia (HR=1.64; 95% CI: 1.19, 2.26) and other related dementia (HR=1.49; 95% CI: 1.34, 1.65) but not Alzheimer’s disease (HR=1.04; 95% CI: 0.87, 1.24) after accounting for competing risks. Mid-life hypertension and stroke were found to have the greatest mid-life impact, mediating 43% and 41% of dementia risk, respectively, highlighting women who may most benefit from close surveillance and early preventive and clinical interventions.

Protocol for #iBeatCRC: a community-based intervention to increase early-onset colorectal cancer awareness using a sequential explanatory mixed-methods approach

IntroductionTh last two decades have seen a twofold increase in colorectal cancer (CRC) incidence among individuals under the recommended screening age of 50 years. Although the origin of this early-onset CRC (EOCRC) spike remains unknown, prior studies have reported that EOCRC harbours a distinct molecular and clinical phenotype in younger individuals. The sharp increase in EOCRC incidence rates may be attributable to a complex interplay of factors, including race; lifestyle; and ecological, sociodemographic and geographical factors. However, more research that address psychosocial experiences and accounts for lifestyle-related behaviours before, during and after an EOCRC diagnosis are warranted. This study aims to develop and pilot test a theory-driven, community-based intervention to increase awareness of EOCRC, reduce its associated risk factors and improve early detection among adults aged 18–49 years.Methods and analysisGuided by the Behaviour Change Wheel, we will use a multistage mixed-methods study design. We will pilot a sequential mixed-methods intervention study as follows: (1) First, we will analyse linked quantitative data from the Utah Cancer Registry and National Cancer Institute Surveillance, Epidemiology and End Results registry, linked to state-wide demographic and vital records in the Utah Population Database to identify EOCRC hotspots in Utah by examining the EOCRC incidence and survival variance explained by personal and county-level factors. (2) Next, we will conduct one-on-one interviews with 20 EOCRC survivors residing in EOCRC hotspots to ascertain psychosocial and lifestyle challenges that accompany an EOCRC diagnosis. (3) Finally, we will consider existing evidence-based approaches, our integrated results (quantitative +qualitative) and community action board input to design a community-based intervention to increase EOCRC awareness that can feasibly be delivered by means of outdoor mass media, and via social media. We will pilot the multicomponent media campaign with a quasiexperimental design among 17 EOCRC hotspot residents and 17 EOCRC ‘coldspot’ residents.Ethics and disseminationEthics approval was obtained from the University of Utah Institutional Review Board (IRB_00138357). Signed informed consent will be obtained from all participants prior to any data collection. Study results will be disseminated through CRC community blogs, targeted infographics, conference presentations at national and international professional conferences and publications in peer-reviewed journals. Final intervention-specific data will be available on reasonable request from the corresponding author.Trial registration numberNCT04715074.

Patterns of use and trends in the use of medications for the control of COPD in a cohort of Colombian patients, 2017-2019 v1

Introduction: Chronic obstructive pulmonary disease (COPD) affects approximately 174 million people worldwide.The objective was to determine the trends of the use of medications for COPD in a group of Colombian patients. Methods: This was a retrospective study on prescription patterns of bronchodilators and other medications used in COPD from a population database with follow-up at 12 and 24 months. Patients older than 18 years of age of any sex who had COPD between 2017 and 2019 were included. Sociodemographic variables, medications, treatment schedules for COPD, comorbidities, comedications, and the specialty of the prescriber were considered. Results: A total of 9,476 people with a diagnosis of COPD were evaluated. They had a mean age of 75.9 ± 10.7 years, 50.1% were men, and 86.8% were prescribed by a general practitioner. At the beginning of the follow-up, on average, they received 1.6 medications/patient, mainly short-acting antimuscarinics (3784; 39.9%), followed by short-acting β-agonists (2997, 31.6%) and inhaled corticosteroids (ICS) (2239, 23.6%), but 5083 (53.6%) patients received a long-acting bronchodilator. At the beginning of the follow-up, 645 (6.8%) patients were put on triple therapy with antimuscarinics, β-agonists, and ICS, and at 12 months, this rose to 1388 (20.6%). A total of 57.9% had comorbidities, most often hypertension (44.4%). Conclusions: This group of patients with COPD treated in Colombia frequently received short-acting bronchodilators and ICS, but a growing proportion are undergoing controlled therapy with long-acting bronchodilators, a situation that can improve the indicators of morbidity, exacerbations, and hospitalization.

Treatment Results for Stage III Laryngeal Cancer: Analysis of a Populational Database Using Propensity Scores

Introduction Treatment of stage III laryngeal cancer suffered a major paradigm change with surgery being substituted by radiation therapy with chemotherapy. Objective To evaluate the oncological outcome of different treatment modalities for stage III laryngeal cancer using a population database. Methods A population database representing patients treated in the state of São Paulo, Brazil, was analyzed. Demographic, clinical and treatment variables were included, and the outcomes of interest were disease-specific and overall survival. Propensity score with nearest neighbor matching was used to compensate for imbalances in treatment groups. Results We retrieved data from 1,804 patients. In multivariate analysis, age, female gender, payment source, clinical N stage (cN) stages, and treatment modality were significant for disease-specific and overall survival. Patients submitted to surgery treatment had a significantly better disease-specific (p < 0.001) and overall survival (p < 0.001) compared with chemoradiation. Propensity score matching was based on cN stage, gender, age, topography, and payment modality, and allowed the pairing of 685 patients from each treatment modality. There was a significant difference in disease-specific survival favoring surgery-based treatment (p = 0.017). Conclusion The treatment choice has a significant impact on survival in patients with stage III laryngeal cancer with surgery-based treatment being superior to chemoradiotherapy (CRT).

Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination

Pathogenic germline mutations in the RAD51 paralog genes RAD51C and RAD51D, are known to confer susceptibility to ovarian and triple-negative breast cancer. Here, we investigated whether germline loss-of-function variants affecting another RAD51 paralog gene, RAD51B, are also associated with breast and ovarian cancer. Among 3422 consecutively accrued breast and ovarian cancer patients consented to tumor/germline sequencing, the observed carrier frequency of loss-of-function germline RAD51B variants was significantly higher than control cases from the gnomAD population database (0.26% vs 0.09%), with an odds ratio of 2.69 (95% CI: 1.4–5.3). Furthermore, we demonstrate that tumors harboring biallelic RAD51B alteration are deficient in homologous recombination DNA repair deficiency (HRD), as evidenced by analysis of sequencing data and in vitro functional assays. Our findings suggest that RAD51B should be considered as an addition to clinical germline testing panels for breast and ovarian cancer susceptibility.

Summary of Utah Project on Exfoliation Syndrome (UPEXS): using a large database to identify systemic comorbidities

The purpose of the Utah Project on Exfoliation Syndrome (UPEXS) is to identify associations between exfoliation syndrome (XFS) and other diseases that share the commonality of abnormalities in elastin and Lysyl Oxidase-Like 1 gene regulation. The UPEXS is unique because it uses the Utah Population Database, which is linked to the Utah genealogy, that contains a compilation of large pedigrees of most families in the state of Utah that go back multiple generations (3 to ≥11). The health and medical records of these family members are linked to vital records and can be used effectively in studies focused on genetic disorders like XFS, where familial clustering of a disorder is a trend. There is increasing evidence that patients with XFS have a higher risk of certain systemic disorders that reflect the systemic tissue abnormalities of XFS. Epidemiological studies focused on patients with XFS have shown that there is an increased risk of these individuals developing other pathologies that have abnormalities in extracellular matrix metabolism and repair. UPEXS has focused on suspected comorbidities that involve abnormalities in elastin maintenance, a protein that plays a role in the makeup of the extracellular matrix. In this paper, the results from the analysis of chronic obstructive pulmonary disease, inguinal hernias, pelvic organ prolapse, obstructive sleep apnoea and atrial fibrillation are summarised along with the utility of using such a large dataset.

Gene Mutations for Cystic Fibrosis and Predisposition to Chronic Rhinosinusitis in Chinese Children

Background: Chronic Rhinosinusitis (CRS) is a common disease in children. In recent years, a new airway epithelial ionocyte has been discovered and is closely related to the expression of cystic fibrosis transmembrane conductance regulator (CFTR), which provides new ideas for the study of the mechanism of CRS. However, the carrying status of the CFTR mutant gene in the Chinese population is not clear. Objective: To study the frequency and mutations of CFTR and FOXI1 (ForkheadBoxI1) in Chinese children with CRS, and to analyze whether they are predisposed to CRS. Methods: A controlled case study was conducted from 2020 to 2021. The CFTR and FOXI1 genomes of 46 children with CRS and 23 children with no history of CRS from the Chinese mainland area were sequenced, and the relationship between mutation rate and the disease were analyzed. Results: 13 CFTR gene mutation sites’ carrying rate in the CRS group was higher than the control group, and 2 of them was significantly higher than that in the East Asian population database. The children who had a history of recurrent upper respiratory tract infection carried CFTR gene mutations associated with the pathogenesis. There was no difference in the carrying of FOXI1 mutation between the two groups. Conclusion: The incidence of CF mutation is higher in Chinese children with CRS who have no history of Cystic Fibrosis (CF). c.650A> G (p.E217G) and c.1950C> A (P. F 650 L) and may play a role in the development of CRS conditions in children in China.