Helping Cancer Survivors Return to Work

Work limitations due to health problems can range from mild or transient limitations to persistent, long‐term dysfunction and can lead to employment instability, underemployment, and even loss of employment. In fact, compared with a healthy matched control population, cancer survivors are 1.37 times more likely to be unemployed. Because patients with metastatic disease are particularly vulnerable, proactive discussion regarding the potential impact of treatment on employment and work outcomes may be beneficial. However, employment and financial toxicity are not topics that clinicians are necessarily trained to address. Financial counselors or patient navigators may be better able to offer a personalized approach and help survivors navigate the complex resources that are involved. Additional research into cancer‐related work outcomes is needed.

Severity of congenital Long QT Syndrome disease onset and risk of depression, anxiety, and mortality: a nationwide study

Introduction The congenital Long QT Syndrome (cLQTS) is associated with an increased risk of sudden cardiac death (SCD). Thus, cLQTS patients are susceptible to develop depression or anxiety, both of which have been associated with poor outcomes including risk of mortality. Aim We examined if a cLQTS diagnosis and the severity of cLQTS disease onset was associated with an increased risk of depression, anxiety, and all-cause mortality compared with a matched control population. Methods Using Danish nationwide registries and inherited cardiac disease clinics, we identified all patients with known cLQTS (1994–2016) who were ≥18 years at the time of diagnosis. The disease onset for cLQTS was identified as asymptomatic, ventricular tachycardia [VT]/ syncope, aborted SCD [aSCD], or unknown (i.e. no available information). After cLQTS diagnosis, we determined the risk of depression (i.e. depression diagnosis or prescription of antidepressants), anxiety (i.e. anxiety diagnosis or prescription of anxiolytics), and mortality using multivariable Cox proportional hazards regression. Patients were followed for three years. An age and gender matched control population was identified (matching 1:4). Competing risk analysis with death as competing risk was used to generate cumulative incidence plots. Results Overall, 428 cLQTS patients were identified of which 107/428 (25%) developed depression or anxiety after being diagnosed with cLQTS compared with 285/1712 (16.6%) from the control population (p<0.001). The severity of disease onset was identified for 229/428 (55%) cLQTS patients; 104 (24%) were asymptomatic, 89 (21%) had VT/ syncope, and 36 (8.4%) had aSCD. A graded relationship between the severity of cLQTS disease onset and risk of depression or anxiety was identified (Figure 1). In multivariable models, patients with aSCD as disease onset had a higher risk of developing depression or anxiety compared with asymptomatic cLQTS patients (HR=2.34, CI: 1.03–5.32). Furthermore, previous depression (HR=6.38, CI: 4.80–8.48) and anxiety (HR=4.20, CI: 3.15–5.59) was found as associated risk factors. However, no risk was associated with concurrent treatment with beta-blockers (HR=1.23, CI: 0.90–1.69). During follow-up, 8 cLQTS patients died of which 4 had developed depression or anxiety (50%). No significant association between all-cause mortality and depression or anxiety was found, although numbers were low (P=0.22). Conclusion The prevalence of depression and anxiety was high among cLQTS patients after diagnosis. Moreover, a graded relationship between severity of disease onset and risk of depression or anxiety was identified. These findings highlight a need for increased awareness following a cLQTS diagnosis in order to reduce the risk of adverse outcomes. Cumulative incidence curve Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Fund of Rigshospitalet

Abstract P156: Assessing the Effect of the Heart of New Ulm Project: a Population-Based Program to Reduce Cardiovascular Disease

Background: Despite a highly recognized priority for public health and healthcare to implement population-level strategies to reduce the burden of cardiovascular disease (CVD), limited evidence exists on the most effective strategies. Data collection and evaluation of large scale, community based-prevention programs can be challenging and costly to achieve. The Heart of New Ulm (HONU) Project, begun in 2009, is a population-based initiative with healthcare, community, and workplace interventions addressing multiple levels of the social-ecological model designed to reduce modifiable CVD risk factors in rural New Ulm, MN. The community is served by one health system, enabling the use of electronic health record (EHR) data for surveillance. Objective: To assess trends for CVD risk factors, events, and healthcare utilization for New Ulm residents compared to a matched control population. Methods: We matched New Ulm residents (n = 4,077) with controls (n = 4,077) from a regional community served by the same health system using refined covariate balance techniques to match on baseline demographics, CVD risk factors, and health care utilization. Mixed effects longitudinal models with adjustment for age and gender, and an interaction for time by community, were run. Model based estimates were constructed for the entire cohort at each time period. Results: Over the first 6 years of the HONU Project,blood pressure, LDL, total cholesterol, and triglycerides were managed better in New Ulm than the matched comparison community. The proportion of New Ulm residents with controlled blood pressure increased by 6.2 percentage points while the control group increased by 2 points. 10-year ASCVD risk scores showed less decline for New Ulm residents than controls (16 vs. 18.4). The intervention and control groups did not differ with regard to inpatient stays, CVD events, smoking, or glucose. Conclusions: Compared to a matched control population, we found improved control of CVD risk factors in the New Ulm Population exposed to the HONU Project.

High Prevalence of Peripheral Artery Occlusive Disease (PAOD) Among Patients with Chronic Myeloid Leukemia (CML) Receiving Tyrosine Kinase Inhibitors (TKIs): A Cross-Sectional Study

Background: Although TKIs become the standard of care in CML, the long-term complication has not been well recognized. There were reports of nilotinib associated metabolic derangements including diabetes and PAOD while these complications in other TKIs have not been well recognized. Objectives: To compare the prevalence of PAOD among CML patients and matched-control population. Methods: A cross-sectional case control study was conducted among CML patients receiving TKIs at Chiang Mai University Hospital between February to December 2014. The control group was matched by age, sex and diabetes. Screening PAOD using Fukuda VS-1500 to measure ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) for arterial stiffness were performed in both groups. The cutoff value of pathologic ABI and CAVI were less than 0.9 and higher than 8, respectively. Results: Seventy-eight CML patients and 156 matched-control population(1:2 ratio) were included. For CML patients, the median age was 55 years (21-86). Atherosclerotic risks including hypertension(20.5%), diabetes(12.8%), dyslipidemia(26.9%), metabolic syndrome(19.2%) and smoking(2.6%). Sixty-one patients(78.2%) were on imatinib, all as first-line, 13 patients(16.7%) on nilotinib (7.7%first-line, 92.3%second-line) while 4 patients(5.2%) were on dasatinib(all third-line). Median duration of imatinib, nilotinib and dasatinib treatment were 89.6, 46.7 and 22.1 months, respectively. The prevalence of pathologic ABI and CAVI were 9.0% and 26.7%, respectively. Patients receiving nilotinib had highest prevalence of abnormal ABI of 30.7% while patients receiving imatinib and dasatinib had abnormal ABI of 5% and 0%, respectively (p=0.004). Abnormal arterial stiffness by CAVI in nilotinib users were 15.4% compared to 27.8% and 50% in imatinib and dasatinib (p=0.815). Patients with CML had higher prevalence of pathologic ABI than in control group with an odds ratio(OR) of 2.09(95%CI 0.71-6.21, p=0.181). The only factor independently associated with pathologic ABI was level of HbA1C over 7 g/dl [OR2.41(95%CI 1.11-5.25; p=0.026)]. Age over 60 years [OR 3.95(95%CI 1.22-12.73, p=0.022)] and fasting plasma glucose over 126 mg/dl [OR 7.96(95%CI 1.21-52.26, p=0.031)] were independently associated with pathologic CAVI. Conclusions: The prevalence of PAOD by using ABI was higher among CML patients than in control population. CML patients receiving TKIs who have diabetes and older than 60 years old have a higher chance of developing PAOD and should be carefully monitored. Disclosures No relevant conflicts of interest to declare.

Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism

Objective: To determine the frequency of rare nucleotide variants in GNRHR and GPR54 in a large cohort of probands (n = 166) with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), characterized by mode of inheritance, testicular volume, and presence or absence of endogenous LH pulsations. Methods: Whenever possible, probands answered detailed questionnaires, underwent full physical exams, and underwent q 10-min frequent blood sampling for LH. Exons segments for GNRHR and GPR54 were screened for mutations. Nucleotide changes were identified as rare variants if they occurred at less than 1% frequency in an ethnically matched control population. Results: Sixty-two percent of male probands were classified as sporadic, meaning that no other family members had delayed puberty or nIHH. In contrast, 61% of female probands were from familial pedigrees, with either autosomal dominant or autosomal recessive inheritance. Patients displayed a broad spectrum of disease severity based on testicular size and endogenous LH pulsations. Twenty-four rare variants were identified in GNRHR (within 15 probands) and seven rare variants in GPR54 (within five probands). Conclusions: Rare variants in GNRHR are more common than GPR54 in a nIHH population.