Employment benefits and job retention: evidence among patients with colorectal cancer

A “health shock,” that is, a large, unanticipated adverse health event, can have long‐term financial implications for patients and their families. Colorectal cancer is the third most commonly diagnosed cancer among men and women and is an example of a specific health shock. We examined whether specific benefits (employer‐based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer. In 2011–14, we surveyed patients with Stage III colorectal cancer from two representative SEER registries. The final sample was 1301 patients (68% survey response rate). For this study, we excluded 735 respondents who were not employed and 20 with unknown employment status. The final analytic sample included 546 respondents. Job retention in the year following diagnosis was assessed, and multivariable logistic regression was used to evaluate associations between job retention and access to specific employment benefits. Employer‐based health insurance (OR = 2.97; 95% CI = 1.56–6.01; P = 0.003) and paid sick leave (OR = 2.93; 95% CI = 1.23–6.98; P = 0.015) were significantly associated with job retention, after adjusting for sociodemographic, clinical, geographic, and job characteristics.A “health shock,” that is, a large, unanticipated adverse health event, can have long‐term financial implications for patients and their families. We examined whether specific benefits (employer‐based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer, an example of a specific health shock. Employer‐based health insurance and paid sick leave were associated with job retention.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142914/1/cam41371_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142914/2/cam41371.pd

The accuracy of chemotherapy ascertainment among colorectal cancer patients in the surveillance, epidemiology, and end results registry program

Abstract Background Surveillance, Epidemiology, and End Results (SEER) public research database does not include chemotherapy data due to concerns for incomplete ascertainment. To compensate for perceived lack of data quality many researchers use SEER-Medicare linked data, limiting studies to persons over age 65. We sought to determine current SEER ascertainment of chemotherapy receipt in two relatively large SEER registries compared to patient-reported receipt and to assess patterns of under-ascertainment. Methods In 2011–14, we surveyed patients with Stage III colorectal cancer reported to the Georgia and Metropolitan Detroit SEER registries. 1301/1909 eligible patients responded (68% response rate). Survey responses regarding treatment and sociodemographic factors were merged with SEER data. We compared patient-reported chemotherapy receipt with SEER recorded chemotherapy receipt. We estimated multivariable regression models to assess associations of under-ascertainment in SEER. Results Eighty-five percent of patients reported chemotherapy receipt. Among those, 10% (n = 104) were under-ascertained in SEER (coded as not receiving chemotherapy). In unadjusted analyses, under-ascertainment was more common for older patients (11.8% age 76+ vs. < 9% for all other ages, p = 0.01) and varied with SEER registries (10.2% Detroit vs. 6.8% Georgia; p = 0.04). On multivariable analyses, chemotherapy under-ascertainment did not vary significantly by any patient attributes. Conclusion We found a 10% rate of under-ascertainment of adjuvant chemotherapy for resected, stage III colorectal cancer in two SEER registries. Chemotherapy under-ascertainment did not disproportionately affect any patient subgroups. Use of SEER data from select registries is an important resource for researchers investigating contemporary chemotherapy receipt and outcomes.https://deepblue.lib.umich.edu/bitstream/2027.42/143192/1/12885_2018_Article_4405.pd

Association of Cumulative Social Risk and Social Support With Receipt of Chemotherapy Among Patients With Advanced Colorectal Cancer

Importance: Approximately 38% of patients with advanced colorectal cancer do not receive chemotherapy. Objective: To determine whether cumulative social risk (ie, multiple co-occurring sociodemographic risk factors) is associated with lower receipt of chemotherapy among patients with advanced colorectal cancer and whether social support would moderate this association. Design, Setting, and Participants: This cross-sectional, population-based, mailed survey study was conducted from 2012 to 2014. Participants were recruited between 2011 and 2014 from all adults within 1 year after diagnosis of stage III colorectal cancer in the Detroit, Michigan, and State of Georgia Surveillance, Epidemiology, End-Results cancer registries. Patients were eligible if they were aged 18 years or older, had undergone surgery 4 or more months ago, did not have stage IV cancer, and resided in the registry catchment areas. Data analyses were conducted from March 2017 to April 2021. Main Outcomes and Measures: The primary outcome was receipt of chemotherapy. Cumulative social risk represented a sum of 8 risk factors with the potential to drain resources from participants\u27 cancer treatment (marital status, employment, annual income, health insurance, comorbidities, health literacy, adult caregiving, and perceived discrimination). Social support was operationalized as emotional support related to colorectal cancer diagnosis. Results: Surveys were mailed to 1909 eligible patients; 1301 completed the survey (response rate, 68%). A total of 1087 participants with complete data for key variables were included in the sample (503 women [46%]; mean [SD] age, 64 [13] years). Participants with 3 or more risk factors were less likely to receive chemotherapy than participants with 0 risk factors (3 factors, odds ratio [OR], 0.48 [95% CI, 0.26-0.87]; 4 factors, OR, 0.41 [95% CI, 0.21-0.78]; 5 factors, OR, 0.42 [95% CI, 0.20-0.87]; ≥6 factors, OR, 0.22 [95% CI, 0.09-0.55]). Participants with 2 or more support sources had higher odds of undergoing chemotherapy than those without social support (2 sources, OR, 3.05 [95% CI, 1.36-6.85]; 3 sources, OR, 3.24 [95% CI, 1.48-7.08]; 4 sources, OR, 3.69 [95% CI, 1.71-7.97]; 5 sources, OR, 4.40 [95% CI, 1.98-9.75]; ≥6 sources, OR 5.95 [95% CI, 2.58-13.74]). Within each social support level, participants were less likely to receive chemotherapy as cumulative social risk increased. Conclusions and Relevance: Cumulative social risk was associated with reduced receipt of chemotherapy. These associations were mitigated by social support. Assessing cumulative social risk may identify patients with colorectal cancer who are at higher risk for omitting chemotherapy who can be targeted for support programs to address social disadvantage and increase social support

How do men in the United Kingdom decide to dispose of banked sperm following cancer treatment?

Current policy in the UK recommends that men bank sperm prior to cancer treatment, but very few return to use it for reproductive purposes or agree to elective disposal even when their fertility recovers and their families are complete. We assessed the demographic, medical and psychological variables that influence the decision to dispose by contacting men (n = 499) who banked sperm more than five years previously, and asked them to complete questionnaires about their views on sperm banking, fertility and disposal. From 193 responses (38.7% response rate), 19 men (9.8%) requested disposal within four months of completing the questionnaire. Compared with men who wanted their sperm to remain in storage, they were significantly more confident that their fertility had recovered (OR = 1.78, 95% CI = 1.05-3.03, p = 0.034), saw fertility monitoring (semen analysis) as less important (OR = 0.61, 95% CI = 0.39-0.94, p = 0.026), held more positive attitudes to disposal (OR = 5.71, 95% CI = 2.89-11.27, p < 0.001), were more likely to have experienced adverse treatment side-effects (OR = 4.37, CI = 1.61-11.85, p = 0.004) and had less desire for children in the future (OR = 0.41, 95% CI = 0.26-0.64, p < 0.001). Information about men's reasons to dispose of banked sperm may be helpful in devising new strategies to encourage men to engage with sperm banking clinics and make timely decisions about the fate of their samples

Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol

Background: Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis.Methods: We are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrolment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported.Discussion: Two published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000326099

Myosin VI in PC12 cells plays important roles in cell migration and proliferation but not in catecholamine secretion

Myosin VI (MVI) is the only known myosin walking towards minus end of actin filaments and is believed to play distinct role(s) than other myosins. We addressed a role of this unique motor in secretory PC12 cells, derived from rat adrenal medulla pheochromocytoma using cell lines with reduced MVI synthesis (produced by means of siRNA). Decrease of MVI expression caused severe changes in cell size and morphology, and profound defects in actin cytoskeleton organization and Golgi structure. Also, significant inhibition of cell migration as well as cell proliferation was observed. Flow cytometric analysis revealed that MVI-deficient cells were arrested in G0/G1 phase of the cell cycle but did not undergo increased senescence as compared with control cells. Also, neither polyploidy nor aneuploidy were detected. Surprisingly, no significant effect on noradrenaline secretion was observed. These data indicate that in PC12 cells MVI is involved in cell migration and proliferation but is not crucial for stimulation-dependent catecholamine release

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (&gt;250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization