Pilot Trial of Streamlined Genetic Education and Traceback Genetic Testing in Prostate Cancer Survivors.

BACKGROUND: Germline genetic testing is recommended for men with metastatic or high-risk prostate cancer to inform treatment and risk management for other cancers and inform genetic testing in at-risk relatives. However, relatively few patients with prostate cancer undergo genetic testing. Given the low rate of testing and increasing demands on genetic service providers, strategies are needed that reduce barriers to testing while conserving genetic counseling resources. The primary goal of this study was to determine whether a proactive and streamlined "traceback" approach could yield increased genetic testing participation among prostate cancer survivors. METHODS: We randomized 107 survivors of metastatic and high-risk prostate cancer to streamlined testing (ST) versus enhanced usual care (EUC). ST participants were proactively provided with print genetic education materials and the option to proceed to genetic testing without pre-test genetic counseling. EUC participants were sent a letter from their physician advising them of their eligibility for genetic testing and recommending they schedule genetic counseling. The primary outcome was genetic testing participation. Secondary outcomes were distress, knowledge, decision satisfaction, and regret. RESULTS: In the ST group, 41.5% of participants completed genetic testing compared with 27.8% in the EUC group. After adjusting for education and marital status, the odds of testing were more than twice as high for the ST group as for the EUC group (odds ratio, 2.57; 95% CI, 1.05-6.29). The groups did not differ on any of the psychosocial outcomes at the 3-month follow-up. CONCLUSIONS: Proactive outreach paired with streamlined genetic testing delivery may be a safe, effective, and resource-efficient approach to facilitate traceback genetic testing in prostate cancer survivors.

Incidence and Durability of SARS-CoV-2 Antibodies in Patients with Cancer and Health Care Workers following the First Wave of the Pandemic.

BACKGROUND: Patients with cancer and health care workers (HCW) are at higher risk for SARS-CoV-2 infection. There are limited data regarding the rate of symptomatic versus asymptomatic infection and subsequent seropositivity in both populations. METHODS: We performed a prospective study of patients and HCW across two institutions during the first wave of the pandemic to analyze the prevalence of SARS-CoV-2 antibodies, the extent of associated symptoms, and durability of serologic response. RESULTS: In 1,953 persons (733 patients and 1,220 HCW), overall seropositivity rates for 3.1% patients (95% CI 2.0-4.7) and 3.7% HCW (95% CI 2.7-4.9, p=0.520), were similar. Each institutions' seropositivity rates were numerically higher in HCW than patients. Non-Hispanic Whites and Asians had lower antibody rates (2.8%, 95% CI 2.0-3.8 and 3.3%, 95% CI 1.2-7.0) compared to Hispanics (6.9%, 95% CI 3.4-12.4) and non-Hispanic Blacks (5.9%, 95% CI 3.3-9.7), p < 0.001. Among persons with a positive SARS-CoV-2 antibody, 87% of patients and 56% of HCW did not recall having had a fever. Among HCW, administrative and technical personnel were most likely to be seropositive. The rate of persistent seropositivity at 3 months was similar between patients and HCW and was not influenced by the reporting of fever, cancer type, or therapy. CONCLUSION: These data suggest that patients are not at higher risk for febrile SARS-CoV-2 infections or more transient immunity than HCWs. Furthermore, racial differences and lack of association with the extent of HCW contact with COVID-19 patients suggest that community rather than hospital virus exposure was a source of many infections.

Medical Complications of Anorexia Nervosa.

OBJECTIVE: The purpose of this study was to describe the medical complications of anorexia nervosa (AN) to enable a consult-liaison psychiatrist to be familiar with these complications when involved with the care of a hospitalized patient with AN. METHODS: Comprehensive PubMed search of English language publications of adult patients with AN was carried out using keywords, phrases, and medical subject headings of anorexia nervosa-medical complications, cardiac, osteoporosis, gastrointestinal, hematological, and endocrine. The database search was restricted by time of publication of studies from 2005 to 2020. RESULTS: Every organ system can be adversely affected by AN. Most are fully reversible with time and informed medical care. A multidisciplinary team is needed to optimally care for patients who are hospitalized as a result of the medical complications of their AN. CONCLUSIONS: Consult-liaison psychiatrists are asked to help in the care of patients with AN who are admitted to a hospital because of a medical complication of their illness. Being familiar with these complications and their treatments will optimize their hospital stays and the care provided. In addition, involving other relevant ancillary services is an important care consideration.

Intrapartum Group B Streptococcus Antibiotic Prophylaxis in Penicillin Allergic Pregnant Women.

Objectives To estimate the prevalence of and identify modifiable risk factors for alternative antibiotics for group B Streptococcus (GBS) prophylaxis in penicillin-allergic women. Methods Retrospective cohort study of pregnant women within a health care network from January 1, 2014, to December 31, 2017. Included women were GBS colonized, delivered at ≥ 37 weeks' gestation, and reported penicillin/cephalosporin allergy. The primary outcome was the use of alternate antibiotics GBS prophylaxis, defined per Centers for Disease Control and Prevention guidelines as antibiotics other than penicillin, ampicillin, or cefazolin. Results We identified 190 GBS-colonized pregnant women self-reporting a penicillin/cephalosporin allergy; 5% reported anaphylaxis, 44% high-risk symptoms (isolated hives, shortness of breath, swelling, or vomiting), and 51% low-risk symptoms (isolated rash, itching, or nausea). Two-thirds (63%) had alternative antibiotic prophylaxis. In adjusted analyses, nonwhite race (adjusted odds ratio [aOR]: 2.42; 95% confidence interval [CI]: 1.19-4.94) and high-risk allergic reaction (aOR: 2.42; 95% CI: 1.30-4.49) were associated with higher odds of alternative antibiotics prophylaxis compared with low-risk allergic reaction. Low-risk allergic reaction group was less likely to receive alternative antibiotic prophylaxis (aOR: 0.36; 95 CI%: 0.19-0.66). Conclusion Alternative antibiotic use for GBS prophylaxis is frequent with penicillin/cephalosporin allergies. Efforts to confirm allergy and perform penicillin hypersensitivity testing may increase compliance with guidelines for antibiotic administration.

Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study.

BACKGROUND: Treatment options are limited for patients with thymic carcinoma. These aggressive tumours are not typically associated with paraneoplastic autoimmune disorders, and strong PD-L1 expression has been reported in thymic epithelial tumours. We aimed to assess the activity of pembrolizumab, a monoclonal antibody that targets PD-1, in patients with advanced thymic carcinoma. METHODS: We completed a single-arm phase 2 study of pembrolizumab in patients with recurrent thymic carcinoma who had progressed after at least one line of chemotherapy. This was a single-centre study performed at Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Key inclusion criteria were an Eastern Cooperative Oncology Group performance status of 0-2, no history of autoimmune disease or other malignancy requiring treatment or laboratory abnormality, and adequate organ function. Patients received 200 mg of pembrolizumab every 3 weeks for up to 2 years. The primary objective of the study was the proportion of patients who had achieved a response assessed with Response Evaluation Criteria in Solid Tumors version 1.1. Analysis was per protocol, in all eligible patients. The study is registered with ClinicalTrials.gov, number NCT02364076, and is closed to accrual; we report the final analysis. FINDINGS: 41 patients were enrolled from March 12, 2015, to Dec 16, 2016, of whom 40 were eligible and evaluable and one was excluded because of elevated liver enzymes at screening. The median follow-up was 20 months (IQR 14-26). The proportion of patients who achieved a response was 22·5% (95% CI 10·8-38·5); one (3%) patient achieved a complete response, eight (20%) patients achieved partial responses, and 21 (53%) patients achieved stable disease. The most common grade 3 or 4 adverse events were increased aspartate aminotransferase and alanine aminotransferase (five [13%] patients each). Six (15%) patients developed severe autoimmune toxicity, including two (5%) patients with myocarditis. There were 17 deaths at the time of analysis, but no deaths due to toxicity. INTERPRETATION: Pembrolizumab is a promising treatment option in patients with thymic carcinoma. Because severe autoimmune disorders are more frequent in thymic carcinoma than in other tumour types, careful monitoring is essential. FUNDING: Merck & Co.

Recruitment methods employed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is a US National Cancer Institute (NCI)-funded randomized controlled trial designed to evaluate whether certain screening tests reduce mortality from prostate, lung, colorectal, and ovarian cancer. To obtain adequate statistical power, it was necessary to enroll over 150,000 healthy volunteers. Recruitment began in 1993 and ended in 2001. PURPOSE: Our goal is to evaluate the success of recruitment methods employed by the 10 PLCO screening centers. We also provide estimates of recruitment yield and cost for our most successful strategy, direct mail. METHODS: Each screening center selected its own methods of recruitment. Methods changed throughout the recruitment period as needed. For this manuscript, representatives from each screening center provided information on methods utilized and their success. RESULTS: In the United States between 1993 and 2001, ten screening centers enrolled 154,934 study participants. Based on participant self-report, an estimated 95% of individuals were recruited by direct mail. Overall, enrollment yield for direct mail was 1.0%. Individual center enrollment yield ranged from 0.7% to 3.8%. Cost per enrolled participant was $9.64-35.38 for direct mail, excluding personnel costs. LIMITATIONS: Numeric data on recruitment processes were not kept consistently at individual screening centers. Numeric data in this manuscript are based on the experiences of 5 of the 10 centers. CONCLUSIONS: Direct mail, using rosters of names and addresses from profit and not-for-profit (including government) organizations, was the most successful and most often used recruitment method. Other recruitment strategies, such as community outreach and use of mass media, can be an important adjunct to direct mail in recruiting minority populations.

Lung cancer screening as a teachable moment for smoking cessation.

BACKGROUND: Lung cancer screening may serve as a 'teachable moment' for smoking cessation, a brief period in which motivation to stop smoking is enhanced. Within the context of two NCI-funded randomized lung screening trials, we conducted an ancillary study to explore the impact of screening on smoking cessation and readiness to stop smoking. METHODS: We accrued a sample of current and former smokers participating at the Georgetown University site of the Lung Screening Study (LSS; N=144) and of the National Lung Screening Trial (NLST; N=169). In each sample, we assessed reasons for trial participation, interest in smoking cessation interventions, motivations for stopping smoking, and the impact of undergoing screening on tobacco use and readiness to stop smoking. Telephone interviews were conducted prior to screening, and 1-month following receipt of the screening result. The samples were analyzed separately due to differences in age and level of nicotine dependence. RESULTS: The majority of the findings were consistent across the two samples. Frequently endorsed reasons for trial participation among both current and former smokers included psychological reasons (e.g., wanting peace of mind about lung cancer) and altruism (e.g., wanting to make a contribution to science). Nicotine replacement therapy and free counseling were the cessation methods that were of most interest, and fear of lung health problems was the most frequently endorsed motivation for quitting smoking. Regarding readiness to stop smoking, approximately 20% were ready to stop in the next 30 days, 45% were ready to stop in the next 6 months, while 35% were not thinking of stopping. At the follow-up, 7% of current smokers at baseline reported abstinence, and 4% of former smokers at baseline reported having relapsed. The findings differed across the two samples when considering the readiness to quit outcome. At the 1-month follow-up of the NLST sample, participants became more ready to stop smoking (p<.05). Screening result did not moderate this finding. In the LSS sample, among younger participants (

Clonogenic endothelial progenitor cells are sensitive to oxidative stress.

Endothelial progenitor cells (EPCs) circulate in the peripheral blood and reside in blood vessel walls. A hierarchy of EPCs exists where progenitors can be discriminated based on their clonogenic potential. EPCs are exposed to oxidative stress during vascular injury as residents of blood vessel walls or as circulating cells homing to sites of neovascularization. Given the links between oxidative injury, endothelial cell dysfunction, and vascular disease, we tested whether EPCs were sensitive to oxidative stress using newly developed clonogenic assays. Strikingly, in contrast to previous reports, we demonstrate that the most proliferative EPCs (high proliferative potential-endothelial colony-forming cells and low proliferative potential-endothelial colony-forming cells) had decreased clonogenic capacity after oxidant treatment. In addition, EPCs exhibited increased apoptosis and diminished tube-forming ability in vitro and in vivo in response to oxidative stress, which was directly linked to activation of a redox-dependent stress-induced kinase pathway. Thus, this study provides novel insights into the effect of oxidative stress on EPCs. Furthermore, this report outlines a framework for understanding how oxidative injury leads to vascular disease and potentially limits the efficacy of transplantation of EPCs into ischemic tissues enriched for reactive oxygen species and oxidized metabolites.

Prevalence of BRCA mutations and founder effect in high-risk Hispanic families.

UNLABELLED: Approximately 12% of the U.S. population is Hispanic, with the majority residing in urban centers such as Los Angeles. The prevalence of BRCA mutations among high-risk Hispanic families is unknown. METHODS: One hundred and ten unrelated probands of Hispanic origin, with a personal or family history of breast and/or ovarian cancer, presented for genetic cancer risk assessment, were enrolled in an Institutional Review Board-approved registry and underwent BRCA testing. Haplotype analyses were done if BRCA mutations were observed in two or more unrelated probands. RESULTS: Mean age at diagnosis was 37 years (range = 23-59) for the 89 (81%) probands with invasive breast cancer. Overall, 34 (30.9%) had deleterious mutations (25 in BRCA1, 9 in BRCA2), 25 (22.7%) had one or more unclassified variants, and 51 (46.4%) had negative results. The mean pretest mutation probability using the Couch model, Myriad model, and BRCAPro was 19.6% (range = 4-77%). The combined average mutation probability was 32.8% for carriers, 15.5% for noncarriers, and 12.9% for variant carriers (P < 0.0001). The most common deleterious mutation was 185delAG (4 of 34, 11.8%). The Hispanic 185delAG carrier families share the same haplotype from D17s1320 through BRCA1, as do two reference Ashkenazi Jewish families. Haplotype analyses of additional recurrent BRCA1 mutations [IVS5+1G>A (n=2),S955X (n = 3), R1443X (n = 3), and 2552delC (n = 2)] also suggest founder effects, with four of six mutations seen almost exclusively in families with Latin American/Caribbean or Spanish ancestry. CONCLUSION: This is the largest study to date of high-risk Hispanic families in the United States. Six recurrent mutations accounted for 47% (16 of 34) of the deleterious mutations in this cohort. The BRCA1185delAG mutation was prevalent (3.6%) in this clinic-based cohort of predominantly Mexican descent, and shared the Ashkenazi Jewish founder haplotype.

Quality of life and trial adherence among participants in the prostate, lung, colorectal, and ovarian cancer screening trial.

BACKGROUND: The National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was designed to examine whether annual screening tests for these four tumor sites result in reduced disease-related mortality. We assessed the impact of trial participation on both health-related quality of life (HRQL) and trial adherence. METHODS: Participants (N = 432; 217 in the control arm and 215 in screening arm) were accrued from the Georgetown University PLCO site from May through December 1998. Screening-arm participants were interviewed by telephone at baseline (prescreening), shortly after notification of screening results (short-term follow-up), and 9 months after notification of screening results (intermediate-term follow up). Control-arm participants completed a baseline and 1-year follow-up assessment. Logistic regression analyses were conducted. RESULTS: Participants reported high levels of HRQL and satisfaction with their decision to participate. Screening-arm participants with abnormal screening results had a higher level of intrusive thoughts about cancer than those with all normal results (odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.3 to 6.3) at the short-term follow-up but not at the intermediate-term follow-up (when abnormal test results were known to be false positive; OR = 1.9, 95% CI = 0.89 to 4.2). Trial adherence was statistically significantly better among participants who had received all normal results in the previous year's screening tests (93.7% versus 78.7%; OR = 3.7, CI = 1.1 to 12.0) than in those who received at least one abnormal result. In the control arm, adherence (defined as returning annual questionnaires) was positively associated with education (OR = 3.4, 95% CI = 1.4 to 8.4) and sex, with women being more likely to return questionnaires than men (OR = 2.1, 95% CI = 1.05 to 4.4). CONCLUSIONS: It is feasible to collect HRQL measures as part of a large cancer screening trial. Prior abnormal screening results were related to short-term HRQL but not to intermediate-term HRQL. Trial adherence was poorer among those who had received previous false-positive results. These results suggest several methods for improving adherence in this and other subgroups.

Specifying cigarette smoking and quitting among people with serious mental illness.

People with serious mental illnesses (SMI) have a high prevalence of cigarette smoking. Details of their smoking and quitting behaviors are needed to create effective interventions. This study aims to describe the smoking and quitting histories, current behaviors, and motivations of an outpatient sample of smokers with SMI. A structured interview and Breathalyzer assessment were administered to 120 smokers from four diverse mental health settings. Participants' smoking and quitting self-report data are presented in combination with demographic and clinical variables; the results provide implications for smoking cessation, amelioration, and prevention interventions and for future research.

The impact of item order on ratings of cancer risk perception.

Although perceived risk is central to most theories of health behavior, there is little consensus on its measurement with regard to item wording, response set, or the number of items to include. In a methodological assessment of perceived risk, we assessed the impact of changing the order of three commonly used perceived risk items: quantitative personal risk, quantitative population risk, and comparative risk. Participants were 432 men and women enrolled in an ancillary study of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Three groups of consecutively enrolled participants responded to the three items in one of three question orders. Results indicated that item order was related to the perceived risk ratings of both ovarian (P < 0.05) and colorectal (P < 0.05) cancers. Perceptions of risk were significantly lower when the comparative rating was made first. The findings suggest that compelling participants to consider their own risk relative to the risk of others results in lower ratings of perceived risk. Although the use of multiple items may provide more information than when only a single method is used, different conclusions may be reached depending on the context in which an item is assessed.