Novotny, Paul

PURPOSE:This randomized, double-blind study sought to understand whether cancer clinical trial consent form verbosity detracts from patients' decision making on trial enrollment.METHODS:This trial tested mock consent forms of 2,000, 4,000, and 6,000 words. The first two comprised the two experimental arms and the third the control arm. Phase II was conducted to identify the promising arm, which, in phase III, was compared with the control arm. Each consent form described the same trial. Eligible adult patients reported a cancer history and English literacy. The primary end point used a patient-reported Likert scale to assess the relationship between information in the consent form and trial decision making.RESULTS:In phase II, 93 patients were accrued and prompted the selection of the 2,000-word consent form for phase III. In phase III, 182 patients were recruited, resulting in 240 total evaluable patients to compare the 2,000-word versus the 6,000-word arm (control). For the primary end point, 103 (84%) and 107 (91%) patients in the 2,000- and 6,000-word arms, respectively, strongly agreed or agreed with the following: “The information in this consent form helped me make a decision about whether or not to enroll in the trial” (two-sided, P = .14). Median time to read each consent form was 8 and 12 minutes, respectively (two-sided, P < .0001). Among those assigned these consent forms, 84% and 73%, respectively (two-sided, P = .04) signed or expressed a willingness to sign.CONCLUSION:This study's primary end point was not met. However, secondary outcomes suggest a need to further study the efficiency and efficacy of shorter consent forms for cancer clinical trial enrollment.

BACKGROUND: Pulmonary rehabilitation is an effective treatment for patients with COPD, but patient uptake and adherence to the current offering of center-based pulmonary rehabilitation is modest due to transportation, access, poverty, and frailty, and even more so in the context of the COVID pandemic. Home-based options have been proposed and were found noninferior to center-based rehabilitation; however, there is a lack of home-based programs, and more understanding is needed. We aimed to test the feasibility, uptake, and adherence to a home-based program for COPD rehabilitation with health coaching. METHODS: We conducted a randomized trial with a wait-list controlled design to evaluate the effects of a home-based program with health coaching on breathlessness in subjects with moderate to severe COPD unable to attend the regular pulmonary rehabilitation program. The 8-week intervention consisted of video-guided exercises to be done 6 times a week and captured with a computer tablet. Health coaching was done weekly over the telephone to review subject activity and symptoms and to provide an opportunity for the subject to define their weekly goals. The primary outcomes were uptake, adherence, and Chronic Respiratory Questionnaire (CRQ) Dyspnea Domain. Secondary outcomes were self-management abilities and CRQ Emotions-Mastery-Fatigue. RESULTS: 154 subjects with moderate to severe COPD were randomized. Subject adherence was 86% to the proposed 6-times a week exercise routine. There ( P = .062) was no significant difference in breathlessness (CRQ dyspnea). There was a significant improvement in self-management abilities ( P < .001). The results of the qualitative interviews showed high levels of acceptability of the program. CONCLUSIONS: The tested home-based rehabilitation program with health coaching was feasible, highly acceptable, showed a high degree of adherence, and improved self-management abilities. This study offers seminal information for home-based rehabilitation programs to design alternative options of rehabilitation to individuals with COPD that cannot attend to the well-established center-based pulmonary rehabilitation. (ClinicalTrials.gov registration NCT02557178.)

8530 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose limiting complication of chemotherapy. Lamotrigine (an anti-convulsant drug) appears to have some benefit when used to treat pain from neuropathy due to various etiologies. Based on these data, we conducted a phase III randomized placebo controlled study to determine the efficacy of lamotrigine in treating symptoms from CIPN. Methods: Patients with CIPN for 1 month or more were randomly assigned to lamotrigine (target dose 300 mg/day, increased by 50 mg/2 weeks) or placebo for 10 weeks. The co-primary endpoints were differences in average CIPN symptoms assessed by pro-rated area under the curve (AUC) of a numerical pain rating scale (NRS) and the Eastern Cooperative Oncology Group sensory neuropathy (ESN) scale. Accrual of 60 patients per group provided t-tests with 80% power to detect a difference of 0.57 standard deviation for each co-primary endpoint (moderate effect size) with a type I error of 0.025. Results: 131patients were enrolled, with complete data available for analysis in 93 (72%). Analyses were limited to this cohort but will be updated. Chemotherapy drugs considered to be causative of the CIPN were vinca alkaloids (30%), taxanes (25%), platinum-agents (7%), combinations (34%), and others (3%). Patients were equally matched with regards to baseline characteristics. Patients who enrolled had severe symptoms, with a baseline median ESN at enrollment of 3 (out of 3) in both groups. Toxicities were similar in both groups, however, more patients discontinued lamotrigine due to toxicities/refusals than those on placebo (32% vs 13% resp; p=0.04) and were therefore less likely to complete the 10 weeks therapy (60% vs. 78% resp, p=0.08). Average AUC of NRS score for patients on lamotrigine and placebo was 30.5 and 33.7 resp (p=0.48). The corresponding average AUC of the ESN scores were 12.4 and 14.5 (p=0.23). The proportions of patients with a 10 point (of 100) improvement in worst pain score (39% vs 36%) and a 1 point change in ESN (25% vs 27%) were similar between the lamotrigine and placebo arms, resp. Conclusions: These results suggest that lamotrigine is not effective for managing pain and symptoms due to CIPN. No significant financial relationships to disclose.

Abstract Background The objective of this study was to evaluate the age at onset and frequency of individual pituitary hormone deficiencies (PHDs) in optic nerve hypoplasia (ONH). Methods We performed a retrospective chart review of patients ≤21 years of age evaluated between 1996 and 2014. Patients were included if they had: (1) ONH diagnosed by an ophthalmologist and/or magnetic resonance imaging (MRI), (2) documentation of pituitary hormone function on at least two separate occasions and (3) at least one PHD documented or a midline abnormality of the brain on MRI. Results Thirty-two patients (18 females, 14 males) were included (median age, 8 years [range, 1.1–21.0 years]). All patients had ONH (bilateral, n = 31; unilateral, n = 1) and at least one midline abnormality of the brain. At least one PHD was present in 75% of patients (n = 24). The remaining 25% of patients (n = 8) did not develop any PHD at least until the last follow-up (<2–8.6 years of follow-up), despite the presence of ONH and a midline abnormality of the brain. The median age (years) at diagnosis of antidiuretic hormone (ADH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and growth hormone (GH) deficiencies was 0.5, 0.6, 0.7 and 1.6, respectively. Twenty-three percent of all PHDs were identified during the neonatal period, 56% by 12 months and 72% by 36 months of age. The latest age at diagnosis of GH, ACTH and TSH deficiencies was 9.6, 9.9 and 12.6 years, respectively. Conclusions The majority of the PHDs in ONH develop within the first 3 years of life. We propose evaluation for endocrinopathies at the time of diagnosis of ONH, with repeat assessment for new deficiencies every 3–4 months until age 3 years and at least semi-annually until growth and puberty are complete.

Background: Socioeconomic status (SES) is an important determinant of disparities in health care and may play a role in end-of-life care and decision-making. The SES is difficult to retrospectively abstract from current electronic medical records and data sets. Objective: Using a validated SES measuring tool derived from home address, the HOUsing-based SocioEconomic Status index, termed HOUSES we wanted to determine whether SES is associated with differences in end-of-life care and decision-making. Design/Setting/Participants: This cross-sectional study utilized a cohort of Olmsted County adult residents admitted to 7 intensive care units (ICUs) at Mayo Rochester between June 1, 2011, and May 31, 2014. Measurements: Multiple variables that reflect decision-making and care at end of life and during critical illness were evaluated, including presence of advance directives and discharge disposition. The SES was measured by individual housing-based SES index (HOUSES index; a composite index derived from real property as a standardized z-score) at the date of admission to the ICU which was then divided into 4 quartiles. The greater HOUSES, the higher SES, outcomes were adjusted for age, 24-hour Acute Physiology and Chronic Health Evaluation III score, sex, race/ethnicity, and insurance. Results: Among the eligible 4134 participants, the addresses of 3393 (82%) were successfully geocoded and formulated into HOUSES. The adjusted odds ratios comparing HOUSES 1 versus 2, 3, and 4 demonstrated lower likelihood of advance directives −0.77(95% CI: 0.63-0.93) and lower likelihood of discharge to home −0.60(95% CI: 1.0.5-0.72). Conclusion: Lower SES, derived from a composite index of housing attributes, was associated with lower rates of advance directives and lower likelihood of discharge to home.

Exercise capacity (EC) is a critical outcome in chronic obstructive lung disease (chronic obstructive pulmonary disease (COPD)). It measures the impact of the disease and the effect of specific interventions like pulmonary rehabilitation (PR). EC determines COPD prognosis and is associated with health-care utilization and quality of life. Field walking tests and cardiopulmonary exercise test (CPET) are two ways to measure EC. The 6-minute walking test (6MWT) is the commonest and easiest field test. CPET has the advantage of assessing maximal aerobic capacity. Determinants of EC include age, gender, breathlessness, and lung function. Previous research suggests that socioeconomic status (SES), a meaningful factor in COPD, may also be associated with EC. However, those findings have not been replicated. We aimed to determine whether SES is an independent factor associated with EC in COPD. For this analysis, we used the National Emphysema Treatment Trial (NETT) database. NETT was a multicenter clinical trial where severe COPD patients were randomized to lung volume reduction surgery or medical therapy. Measures used were taken at baseline, postrehabilitation. Patients self-reported their income and were divided in two groups whether it was less or above US$30,000. Patients with a lower income had worse results in 6MWT ( p < 0.0001). We found an independent association between income and the 6MWT in patients with severe COPD after adjusting for age, gender, lung function, dyspnea, and living conditions ( p < 0.0007). One previous publication stated the relationship between income and EC. Our research confirms and extends previous publications associating EC with income by studying a large and well characterized cohort of severe COPD patients, also addressing EC by two different methods (maximal watts and 6MWT). Our results highlight the importance of addressing social determinants of health such as income when assessing COPD patients.

Purpose There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. Methods We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. Results Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. Conclusion Clinical benefits were associated with symptom self-reporting during cancer care.

Abstract Rationale Cognitive dysfunction has been demonstrated in chronic obstructive pulmonary disease (COPD), but studies are limited to cross-sectional analyses or incompletely characterized populations. Objectives We examined longitudinal changes in sensitive measures of executive function in a well-characterized population of patients with severe COPD. Methods This study was performed on patients enrolled in the National Emphysema Treatment Trial. To assess executive function, we analyzed trail making (TM) A and B times at enrollment in the trial (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after enrollment, adjusted for surgery, marriage status, age, education, income, depression, PaO2, PaCO2, and smoking. Associations with survival and hospitalizations were examined using Cox regression and linear regression models. Measurements and Main Results The average age of the patients was 66.4 years, and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had executive dysfunction. Compared with those who did not, these patients were older, less educated, had higher oxygen use, higher PaCO2, worse quality of life as measured by the St. George’s Respiratory Quotient, reduced well-being, and lower social function. There was no significant change over 2 years in TM A or B times after adjustment for covariables. Changes in TM B times were modestly associated with survival, but changes in TM B − A times were not. Changes in TM scores were not associated with frequency of hospitalization. Lung function, PaO2, smoking, survival, and hospitalizations were not significantly different in those with executive dysfunction. Conclusions In this large population of patients with severe emphysema and heavy cigarette smoking exposure, there was no significant decline over 2 years in cognitive executive function as measured by TM tests. There was no association between executive function impairment and frequency of hospitalization, and there was a possible modest association with survival. It is plausible that cerebrovascular comorbidities explain previously described cognitive pathology in COPD.