Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-Controlled Study of Telotristat Ethyl

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful. Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment. Findings: All 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving ≥ 30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoid syndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo. Implications: Patient interviews revealed that TELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl

Venetoclax combined with low dose cytarabine compared to standard of care intensive chemotherapy for the treatment of favourable risk adult acute myeloid leukaemia (VICTOR): Study protocol for an international, open-label, multicentre, molecularly-guided randomised, phase II trial

Background: For patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC. Methods: VICTOR is an international, two-arm, open-label, multi-centre, non-inferiority, randomised-controlled phase II trial to assess VEN + LDAC compared to standard of care (IC) as first-line treatment in older patients (initially aged ≥ 60 years) with newly diagnosed AML. The trial will recruit patients with a NPM1mutFLT3 ITDneg genotype; those with a favourable risk in relation to the experimental treatment. University of Birmingham is the UK co-ordinating centre, with national hubs in Aarhus University Hospital, Denmark, and Auckland District Health Board, New Zealand. The primary outcome is molecular event-free survival time where an event is defined as failure to achieve morphological complete response (CR) or CR with incomplete blood count recovery after two cycles of therapy; molecular persistence, progression or relapse requiring treatment change; morphological relapse, or; death. Secondary outcomes include cumulative resource use at 12- and 24-months, and QoL as assessed by EORTCQLQ-C30 and EQ-5D-3L at 3-, 6-, 12-, 18- and 24-months. The trial employs an innovative Bayesian design with target sample size of 156 patients aged > 60 years. Discussion: The principle underpinning the VICTOR trial is that the chance of cure for patients in the experimental arm should not be compromised, therefore, an adaptive design with regular checks on accumulating data has been employed, which will allow for a staged expansion of the trial population to include younger patients if, and when, there is sufficient evidence of non-inferiority in older patients. Trial registration: EudraCT: 2020–000,273-24; 21-Aug-2020. ISRCTN: 15,567,173; 08-Dec-2020

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available

Dual enrollment in Tennessee and its effect on persistence and scholarship retention of Tennessee Educational Lottery Scholarship recipients

This study examined dual enrollment participants from fall 2000 to spring 2006 and the effect of dual enrollment on TELS recipients from fall 2004 and fall 2005. Archival data from public colleges and universities in Tennessee was used to conduct the study. One purpose was to identify characteristics of students who participated in dual enrollment in Tennessee. The other purpose was to determine if TELS recipients who had participated in dual enrollment persisted and retained their lottery scholarship at a higher rate than those who did not participate in dual enrollment. Five research questions guided the study. Descriptive statistics identified characteristics of dual enrollment participants and TELS recipients. Fourteen hypotheses were tested using Chi-Square, and logistic regression was used on two hypotheses. The results concluded that there is racial disparity among dual enrollment participants (92.5% white). Overall dual enrollment participants held an average ACT composite of 23.6 and an average high school GPA of 3.5. The majority participated in dual enrollment through community colleges (87%). However, only 19% of dual enrollment participants attended community colleges who received TELS. It was concluded that students who had previously participated in dual enrollment were more likely to persist in the subsequent fall semester and retain their TELS than their nondual TELS counterparts. However, there were no significant differences in GAMS recipients\u27 persistence and scholarship retention in students who had an ACT of 27 or higher and a high school GPA of 3.75 or higher. The study found high school GPA and ACT were predictive values for persistence and TELS retention among students who had previously participated in dual enrollment. High school GPA was the stronger of the two variables

“We Just Take Care of Each Other”: Navigating ‘Chosen Family’ in the Context of Health, Illness, and the Mutual Provision of Care amongst Queer and Transgender Young Adults

&ldquo;Chosen family&rdquo;&mdash;families formed outside of biological or legal (bio-legal) bonds&mdash;is a signature of the queer experience. Therefore, we address the stakes of &ldquo;chosen family&rdquo; for queer and transgender (Q/T) young adults in terms of health, illness and the mutual provision of care. &ldquo;Chosen family&rdquo; is a refuge specifically generated by and for the queer experience, so we draw upon anthropological theory to explore questions of queer kinship in terms of care. We employ a phenomenological approach to semi-structured interviews (n = 11), open coding, and thematic analysis of transcriptions to meet our aims: (1) Develop an understanding of the beliefs and values that form the definition of &ldquo;chosen family&rdquo; for Q/T young adults; and (2) Understand the ways in which &ldquo;chosen family&rdquo; functions in terms of care for health and illness. Several themes emerged, allowing us to better understand the experiences of this population in navigating the concept of &ldquo;chosen family&rdquo; within and beyond health care settings. Emergent themes include: (1) navigating medical systems; (2) leaning on each other; and (3) mutual aid. These findings are explored, as are the implications of findings for how health care professionals can better engage Q/T individuals and their support networks

Impact of wall thickness and saccular geometry on the computational wall stress of descending thoracic aortic aneurysms.

BACKGROUND: Wall stress calculated using finite element analysis has been used to predict rupture risk of aortic aneurysms. Prior models often assume uniform aortic wall thickness and fusiform geometry. We examined the effects of including local wall thickness, intraluminal thrombus, calcifications, and saccular geometry on peak wall stress (PWS) in finite element analysis of descending thoracic aortic aneurysms. METHODS AND RESULTS: Computed tomographic angiography of descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular) underwent 3-dimensional reconstruction with custom algorithms. For each aneurysm, an initial model was constructed with uniform wall thickness. Experimental models explored the addition of variable wall thickness, calcifications, and intraluminal thrombus. Each model was loaded with 120 mm Hg pressure, and von Mises PWS was computed. The mean PWS of uniform wall thickness models was 410 ± 111 kPa. The imposition of variable wall thickness increased PWS (481 ± 126 kPa, P CONCLUSIONS: Incorporation of local wall thickness can significantly increase PWS in finite element analysis models of thoracic aortic aneurysms. Incorporating variable wall thickness, intraluminal thrombus, and calcifications significantly impacts computed PWS of thoracic aneurysms; sophisticated models may, therefore, be more accurate in assessing rupture risk. Saccular aneurysms did not demonstrate a significantly higher normalized PWS than fusiform aneurysms

Identification and characterization of high methane-emitting abandoned oil and gas wells.

Recent measurements of methane emissions from abandoned oil/gas wells show that these wells can be a substantial source of methane to the atmosphere, particularly from a small proportion of high-emitting wells. However, identifying high emitters remains a challenge. We couple 163 well measurements of methane flow rates; ethane, propane, and n-butane concentrations; isotopes of methane; and noble gas concentrations from 88 wells in Pennsylvania with synthesized data from historical documents, field investigations, and state databases. Using our databases, we (i) improve estimates of the number of abandoned wells in Pennsylvania; (ii) characterize key attributes that accompany high emitters, including depth, type, plugging status, and coal area designation; and (iii) estimate attribute-specific and overall methane emissions from abandoned wells. High emitters are best predicted as unplugged gas wells and plugged/vented gas wells in coal areas and appear to be unrelated to the presence of underground natural gas storage areas or unconventional oil/gas production. Repeat measurements over 2 years show that flow rates of high emitters are sustained through time. Our attribute-based methane emission data and our comprehensive estimate of 470,000-750,000 abandoned wells in Pennsylvania result in estimated state-wide emissions of 0.04-0.07 Mt (1012 g) CH4 per year. This estimate represents 5-8% of annual anthropogenic methane emissions in Pennsylvania. Our methodology combining new field measurements with data mining of previously unavailable well attributes and numbers of wells can be used to improve methane emission estimates and prioritize cost-effective mitigation strategies for Pennsylvania and beyond

Saddle-Shaped Annuloplasty Improves Leaflet Coaptation in Repair for Ischemic Mitral Regurgitation

Background. Current repair results for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings are characterized by high IMR recurrence rates. Current annuloplasty rings treat annular dilatation, but they do little to improve (and may actually exacerbate) leaflet tethering. New saddle-shaped annuloplasty rings have been shown to maintain or restore a more physiologic annular and leaflet geometry and function. Using a porcine IMR model, we sought to demonstrate the influence of annuloplasty ring shape on leaflet coaptation. Methods. Eight weeks after posterolateral infarct, eight pigs with grade 2D or higher IMR were randomized to undergo either a 28-mm flat ring annuloplasty (n=4) or a 28-mm saddle-shaped ring annuloplasty (n=4). Realtime three-dimensional echocardiography and a customized image analysis protocol allowed three-dimensional assessment of leaflet coaptation before and after annuloplasty. Results. Total leaflet coaptation area was significantly higher after saddle-shaped ring annuloplasty (109.6 +/- 26.9 mm(2)) compared with flat ring annuloplasty (46.2 +/- 7.7 mm(2), p <0.01). After annuloplasty, total coaptation area decreased by 87.5 mm(2) (or 65%) in the flat annuloplasty group (p = 0.01), whereas total coaptation area increased by 22.2 mm(2) (or 25%) in the saddle-shaped annuloplasty group (p = 0.28). Conclusions. This study shows that the use of undersized saddle-shaped annuloplasty rings in mitral valve repair for IMR improves leaflet coaptation, whereas the use of undersized flat annuloplasty rings worsens leaflet coaptation. Because one of Carpentier's fundamental principles of mitral valve repair (durability) is to create a large surface of coaptation, saddle-shaped annuloplasty may increase repair durability. (C) 2015 by The Society of Thoracic Surgeon

Saddle-Shaped Annuloplasty Improves Leaflet Coaptation in Repair for Ischemic Mitral Regurgitation.

BACKGROUND: Current repair results for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings are characterized by high IMR recurrence rates. Current annuloplasty rings treat annular dilatation, but they do little to improve (and may actually exacerbate) leaflet tethering. New saddle-shaped annuloplasty rings have been shown to maintain or restore a more physiologic annular and leaflet geometry and function. Using a porcine IMR model, we sought to demonstrate the influence of annuloplasty ring shape on leaflet coaptation. METHODS: Eight weeks after posterolateral infarct, eight pigs with grade 2+ or higher IMR were randomized to undergo either a 28-mm flat ring annuloplasty (n = 4) or a 28-mm saddle-shaped ring annuloplasty (n = 4). Real-time three-dimensional echocardiography and a customized image analysis protocol allowed three-dimensional assessment of leaflet coaptation before and after annuloplasty. RESULTS: Total leaflet coaptation area was significantly higher after saddle-shaped ring annuloplasty (109.6 ± 26.9 mm(2)) compared with flat ring annuloplasty (46.2 ± 7.7 mm(2), p CONCLUSIONS: This study shows that the use of undersized saddle-shaped annuloplasty rings in mitral valve repair for IMR improves leaflet coaptation, whereas the use of undersized flat annuloplasty rings worsens leaflet coaptation. Because one of Carpentier\u27s fundamental principles of mitral valve repair (durability) is to create a large surface of coaptation, saddle-shaped annuloplasty may increase repair durability