Burosumab Improves Patient-Reported Outcomes in Adults With Tumor-Induced Osteomalacia: Mixed-Methods Analysis.

Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused by tumors that secrete fibroblast growth factor 23, leading to chronic hypophosphatemia, poor skeletal health, and impaired physical function. In a phase 2 trial (UX023T-CL201; NCT02304367; n = 14), 48 weeks of burosumab treatment restored phosphate homeostasis, with improvements in skeletal health, functional mobility, and patient-reported pain, fatigue, and health-related quality of life (HRQL) (SF-36 v2). Here, we report an exploratory mixed-methods analysis of change from baseline after 144 weeks of burosumab treatment alongside qualitative data from exit interviews with 8 of 14 trial participants to evaluate meaningful treatment effects from a patient perspective. The interview subset (n = 8) reported pain and fatigue and compromised HRQL at baseline. In the interviews, participants reported that compromised HRQL and pain were the most important aspects of the disease to treat; both were considered more bothersome than fatigue and compromised physical function and activities of daily living. Improvements in pain and fatigue after treatment were reported, some of which achieved statistically and/or clinically meaningful thresholds. Furthermore, improvements in SF-36 v2 scores were most pronounced in the Physical Component Score and its Physical Function and Bodily Pain domains. Overall, the interview subset provided descriptions of symptomatic improvement and its clinical meaningfulness, including physical function, participation in activities of daily living, and mental well-being. Thus, this exploratory mixed-methods analysis provides deeper understanding of patients' perception of clinical meaningfulness beyond that articulated in validated patient-reported outcome instruments. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Exploring the Experience of Living with and Managing Presbyopia.

SIGNIFICANCE: Presbyopia typically occurs around 40 years of age and affects approximately one-quarter of the global population. Up to October 2021, there were no approved pharmacotherapies for presbyopia, and common treatments, such as glasses, can have disadvantages for individuals' health-related quality of life. PURPOSE: This study aimed to document the experience of living with and managing presbyopia, identify perspectives on treatment options, and determine whether there is an unmet need in the treatment landscape. METHODS: Coded transcripts of concept elicitation (CE; n = 20) and cognitive debriefing (n = 20) interviews with presbyopic individuals, originally conducted for development of patient-reported outcome instruments, were reanalyzed to identify salient concepts describing participants' experiences with presbyopia treatments. Qualitative ranking exercises assessed participants' preferences for a potential pharmacotherapy vs. existing treatments. RESULTS: Because most concepts were identified with the CE interviews, data reflect CE findings unless otherwise noted. Average age across CE/cognitive debriefing interviews was 49.4 years; a vast majority of participants used glasses for presbyopia treatment. Four themes related to treatment with glasses were identified with the interviews: inconvenience during daily activities, negative physical sensations around the eyes/head, limitations, and undesirable impacts on daily life (e.g., psychosocial). Most commonly, participants reported inconveniences related to forgetting glasses and psychosocial impacts (e.g., feeling/looking older). Strained/tired eyes and limited ability to see at varying distances were also reported. Among participants with near-vision glasses who provided data, two-thirds expressed interest in alternative treatments. In addition, almost three-quarters of the participants ranked hypothetical eye drops as their first or second preferred option, vs. reading glasses, contact lenses, magnifying glasses, and surgery. CONCLUSIONS: This study explored the experience of living with and managing presbyopia and identified limitations and negative impacts of current treatments. Pharmacological development (e.g., eye drops) may fulfill an unmet need in the presbyopia treatment landscape.

NaCl substrates for high temperature processing and transfer of ultrathin materials.

Ultrathin materials often require high temperatures for growth and processing, which cannot be withstood by the substrate underneath. For example, polymers are widely used as a supporting layer but unfortunately have low strain-point temperatures. This is the case of polyethylene terephthalate (PET) which has glass transition and melting temperatures of 76 and 250 °C, respectively. In this paper we propose to use polished salt, a material that can withstand high temperatures during fabrication and, at the same time, can be sacrificed during the transfer onto the final substrates. More specifically, we demonstrate thermal dewetting of Au ultrathin metal films and growth of MoS2 on NaCl at 750 and 650 °C, respectively, and subsequent transfer onto PET films, after which the salt is easily dissolved by water. We believe that the proposed technique can be extended to fabrication of other ultrathin materials, e.g. graphene, as well as final substrates for a wide range of applications, including flexible electronic and optoelectronic devices.

Evaluation and Validation of the Modified Reflux Symptom Questionnaire-Electronic Diary in Patients With Persistent Gastroesophageal Reflux Disease.

OBJECTIVES: This study aimed to examine the validity of the modified Reflux Symptom Questionnaire-electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments. METHODS: Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.gov identifier: NCT02637557) on persistent GERD served to aid in the construction of weekly scores for heartburn severity, regurgitation severity, and total GERD severity. These scores' psychometric properties were also evaluated. RESULTS: Minor modifications were made to the draft mRESQ-eD based on patient feedback to improve interpretability and clarity of the instrument. Psychometric analysis suggested that an 8-item version of the mRESQ-eD was best suited to the clinical data. The internal consistency was found to be high (Coefficient ω = 0.95). Retest reliability and convergent validity were strong for a heartburn weekly severity score, regurgitation weekly severity score, and total GERD severity score. DISCUSSION: The final 8-item mRESQ-eD is a reliable and valid instrument with good psychometric properties for use in clinical trials in patients with persistent GERD. The mRESQ-eD may be considered for inclusion in clinical trials for persistent GERD and potentially positioned, in consultation with Food and Drug Administration, as endpoints to characterize treatment benefit.

Charge transport parameters for carbon based nanohoops and donor-acceptor derivatives.

The effect of donor-acceptor (D-A) moieties on magnitudes such as reorganization energies and electronic couplings in cycloparaphenylene (CPP) carbon based nanohoops (i.e. conjugated organic molecules with cyclic topology) is highlighted via model computations and analysis of the available crystalline structure of N,N-dimethylaza[8]CPP. For the sake of comparison, intra-molecular and inter-molecular charge transport parameters are concomitantly modelled for the recently determined herringbone polymorph of [6]CPP, along with [8]CPP and [12]CPP. The peculiar contribution of low frequency vibrations to intramolecular reorganization energies is also disclosed by computing the Huang-Rhys factors for the investigated [n]CPPs and the N,N-dimethylaza derivative. In contrast with most planar organic semiconductors where the layer in which molecules are herringbone arranged identifies the high-mobility plane, nanohoops disclose inter-layer electronic couplings larger than the intra-layer counterparts. Charge transfer rate constants modelled with three different approaches (Marcus, Marcus-Levich-Jortner and spectral overlap) suggest that D-A nanohoops, owing to orbital localization, may be more efficient for charge transport than [n]CPPs for suitable solid phase arrangements.

Current psychological approaches to the management of chronic pain.

PURPOSE OF REVIEW: To provide a review of the rationale and evidence supporting three frequently used psychosocial interventions for chronic pain: cognitive-behavioral therapy, operant behavioral therapy and self-hypnosis training. We also review recent work in these areas, with an emphasis on the 2006 publishing year. RECENT FINDINGS: Recent clinical trials and laboratory work continue to support the use of cognitive-behavioral therapy and operant behavioral therapy as adjunctive treatments for chronic pain. Notable areas of new research include a novel program of systematic exposure to pain-related fear (such as fear of reinjury) and the adaptation of cognitive-behavioral therapy for special pain groups (e.g. juveniles and those with pain secondary to physical disability). Regarding self-hypnosis training, recent work suggests that hypnosis can provide temporary pain relief to the majority of individuals with chronic pain and that a substantial minority of these patients experience a clinically significant reduction in baseline pain over time. SUMMARY: Cognitive-behavioral therapy and operant behavioral therapy treatments focus on factors that exacerbate or maintain suffering in chronic pain, and should be considered as part of a multidisciplinary treatment paradigm. Self-hypnosis training may also be of benefit, although it appears to be no more (or less) effective than other relaxation strategies that include hypnotic elements.

Burns as a result of assault: associated risk factors, injury characteristics, and outcomes.

The purpose of this study was to identify specific premorbid factors and injury characteristics associated with intentional burn injuries and to compare outcomes for individuals injured by assault and those with unintentional injuries. Participants sustaining major burns from May 1994 to August 2005 and consenting to a multisite, prospective, longitudinal outcome study were included. Etiology of the injury was classified as intentional (i.e., assault) or unintentional. Subjects <18 years old or with self-inflicted burns were excluded. Statistical analysis was performed with t-tests, chi2 tests, and analysis of variance. Eighty patients sustained intentional burn injuries and 1982 subjects sustained nonintentional burn injuries. Compared to patients with nonintentional burns, those with burns related to assault were more likely to be female, black, and unemployed and to have higher rates of premorbid substance use. Between the groups, there were no significant differences in preinjury living situation, education level, history of psychiatric treatment, or hospital length of stay. The intentional-burn group had larger burns and a greater in-hospital mortality rate, and these patients were less likely to be discharged to home. They also demonstrated significantly greater levels of psychological distress during the acute hospitalization but not at follow-up. Understanding the unique characteristics and needs of patients with intentional burn injuries is important because these individuals are less likely to have a steady income and more likely to rely on community social services. Affordable and accessible community-based health services are necessary in order to improve their outcomes.