Assessing the effect of weight and weight loss in obese persons with type 2 diabetes

The objective of this study was to assess specific areas of life in which obesity affects individuals with type 2 diabetes mellitus (T2DM), and changes that obese persons with T2DM experience with weight loss of varying degrees. Thirty in-depth interviews were conducted in persons identified as: age ≥40 years, diagnosed with T2DM for ≥2 years, on oral antihyperglycemic medications >3 months, BMI 30–35 kg/m2, having attempted to lose weight in the last 2 years. Participants (60% female, mean age 53 years, 53% Caucasian, mean BMI 32.2 kg/m2) agreed that 5% weight loss, while not reflective of an ultimate goal, would be meaningful and important; benefits were expected to accrue in physical functioning, self-confidence, blood glucose levels, and motivation to keep losing weight. Participants reported the greatest effect of weight loss on energy, physical activity, mobility, pain, and clothes/appearance. Participants reported weight affecting mood, with feelings of depression and frustration most commonly described. This research indicates that weight loss is likely to affect health-related quality of life in obese individuals with T2DM. Given the purported weight loss benefits of many emerging diabetic medications, it will be important to include measures of weight-related quality of life in future clinical trials of these agents

Understanding the Patient Experience of Hunger and Improved Quality of Life with Setmelanotide Treatment in POMC and LEPR Deficiencies

Introduction In patients with pro-opiomelanocortin (POMC) or leptin receptor (LEPR) deficiency, managing obesity and hyperphagia can be burdensome for patients and caretakers. The impacts on health-related quality of life are under-recognized and are not well characterized. Methods We conducted in-depth qualitative interviews in patients with POMC (n = 3) and LEPR (n = 2) deficiencies participating in an ongoing open-label extension of phase 3 clinical trials with the melanocortin receptor 4 agonist setmelanotide to describe the patient experience of hyperphagia and characterize changes following treatment with setmelanotide. Results Prior to setmelanotide treatment, all five patients described abnormal sensations of hunger with none indicating feeling satiated after meals and also reported that the burden of hyperphagia impacted their families, emotions, and work and/or school functioning. Following setmelanotide treatment, all five patients reported consistent reductions in hunger and weight, decreased eating, and feeling satiated after meals in addition to substantial improvements in each area of functioning they had previously reported. All five patients indicated they were very satisfied with the impact of setmelanotide on their quality of life and would be upset if treatment was discontinued. Conclusions In patients with POMC or LEPR deficiency, hyperphagia and the inability to feel satiety negatively impacted quality of life. By reducing hunger and improving satiety, setmelanotide facilitated important changes in the lives of these patients. This qualitative research study suggests that the impact of setmelanotide goes beyond favorable clinical changes (e.g., weight and hunger) to also include quality of life improvements that are highly meaningful to patients

Psychometric Evaluation of Patient-Reported Outcomes in Irritable Bowel Syndrome Randomized Controlled Trials: A Rome Foundation Report

There is debate about how best to measure patient reported outcomes (PROs) in irritable bowel syndrome (IBS). We pooled data from clinical trials to measure the psychometric properties of IBS endpoints, including binary responses (e.g. “adequate relief”) and 50% improvement in symptom severity

Development and Validation of the Diabetic Foot Ulcer Scale-Short Form (DFS-SF)

Background: The Diabetic Foot Ulcer Scale (DFS) provides comprehensive measurement of the impact of diabetic foot ulcers on patients Objective: To develop and evaluate a short form of the DFS (DFS-SF) to reduce patient burden and the number of outcome measures, and to improve sensitivity to change in clinical condition. Methods: The DFS-SF was created through the analysis of data from a double- blind, placebo-controlled, randomised trial of the efficacy and safety of becaplermin (recombinant human platelet-derived growth factor BB) in the treatment of chronic, full-thickness, neuropathic, diabetic foot ulcers. Using these data, items demonstrating poor psychometric properties were eliminated. Exploratory factor analyses were then conducted to develop a new, more parsimonious scaling algorithm that optimised the internal consistency of the new subscales. Finally, data from two additional clinical trials were used to assess replicability of the DFS-SF subscale structure. Results: The DFS-SF contains a total of 29 items comprising six subscales. The results of both confirmatory and exploratory factor analyses provided support for the scaling algorithm. The DFS-SF subscales showed good internal consistency, reliability and construct validity, and demonstrated sensitivity to ulcer healing. Conclusions: The results of this investigation indicate that the DFS-SF has good psychometric properties and replicability.Diabetic-foot-ulcer, Quality-of-life-rating-scales

Evaluating Minimal Clinically Important Differences for the Acne-Specific Quality of Life Questionnaire

Background: The Acne-Specific Quality of Life Questionnaire (Acne-QoL) is a responsive, reliable and valid instrument developed to measure the impact of facial acne across four dimensions of patient QOL. Score changes on this instrument have been used to report statistically significant treatment advantages for a low-dose oral contraceptive (Estrostep(R)), containing norethisterone (norethindrone) acetate (NA) 1mg and ethinylestradiol (EE) [20, 30, 35mg] as compared with placebo in women with moderate acne vulgaris. However, the question remained if these statistically significant results were also clinically meaningful. Objectives: To evaluate the statistically significant Acne-QoL benefits observed with NA/EE in terms of their clinical significance, and to compare the three different approaches for defining a minimal clinically important difference (MCID) for the Acne-QoL instrument. Methods: Since the optimum method for estimating MCIDs has yet to be established, three different published approaches for determining MCIDs were applied and compared using data from two randomised, double-blind, placebo- controlled studies of the efficacy of NA/EE in the treatment of facial acne. Results: Although the approaches differed substantially, the resulting MCID estimates were comparable. Specifically, the MCID estimates ranged from 0.50-10.3 mean change per item, depending on the domain. The results showed that the statistically significant treatment advantages for NA/EE were also clinically significant. Conclusion: When applied to the change scores present, the results showed that the statistically significant treatment advantages for NA/EE were also clinically significant.Acne, Pharmacoeconomics, Quality-of-life-rating-scales

The Burden of Restless Legs Syndrome: An Assessment of Work Productivity, Sleep, Psychological Distress, and Health Status Among Diagnosed and Undiagnosed Individuals in an Internet-Based Panel

Background: Restless legs syndrome (RLS) affects approximately 10-15% of the general population and has deleterious effects on sleep and subsequent daytime performance. The disorder may also give rise to long-term complications such as psychological distress and diminished quality of life. The condition is often unrecognized or misdiagnosed, and the magnitude of the effects of RLS on the sizeable proportion of undiagnosed (and therefore untreated) individuals has not previously been evaluated. Objectives: This study examined the impact of RLS on overall health status, sleep, psychological functioning, work productivity, and daily activities in individuals with diagnosed and in those with undiagnosed (self-reported) RLS. Methods: An internet-based survey was conducted on a multimillion-member panel of US adults. Eligible participants were currently experiencing RLS symptoms as determined using established diagnostic criteria. Participants provided information related to self-reported RLS diagnosis, treatment, symptom frequency and severity, and responses to validated instruments (Medical Outcomes study [MOS] Short Form 12, version 2 [SF-12v2], MOS Sleep Scale, Center for Epidemiological Studies Depression Scale [CES-D], Work Productivity and Activity Impairment - General Health Questionnaire [WPAI-GH] and Work Limitations Questionnaire [WLQ]). Analysis of co-variance (ANCOVA) models were developed to evaluate the relationships among symptom severity, diagnosis status, age, and sex, and the impact of RLS. Results: Participants included 702 adults with RLS symptoms. Means for the SF-12v2 scores (physical component score_=_35.6, mental component score_=_42.6) were at least 1 standard deviation lower than sex- and age-adjusted general population norms. Participants reported poorer sleep quality scores across each MOS Sleep Scale domain, with differences from published norms of >16 points on 100-point scales, as well as approximately 1 hour less sleep per night on average. A majority (64%) met the cut-off score for depression. Compared with population norms, the sample reported greater limitations in time management, physical demands, mental/interpersonal demands, general work output, and usual activities. Symptom intensity and frequency were shown to be the primary predictors of RLS impact on the various outcomes. Conclusion: These results support previous reports that RLS often goes undiagnosed or misdiagnosed. The results of this survey also suggest that regardless of whether RLS is recognized, the burden of the disorder is substantial, implying a need for improved diagnosis and management of RLS. DOI: 10.2165/1312067-200801030-00007Productivity-costs, Quality-of-life, Restless-legs-syndrome

Use of the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events to assess treatment tolerability in pulmonary arterial hypertension: qualitative patient research findings in current and former users of oral selexipag

Abstract Background Understanding patients’ perspectives regarding drug tolerability, in addition to effectiveness, provides a complete picture of the patient experience and supports more informed therapeutic decision-making. The item library of the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to measure patient-reported frequency, severity, and interference of adverse events (AEs) associated with cancer therapies. This qualitative interview study assessed the suitability of items selected from the PRO-CTCAE library for assessing tolerability of selexipag, a medication targeting the prostacyclin pathway for patients with pulmonary arterial hypertension (PAH). Methods Two rounds of 10 qualitative, web-assisted telephone interviews following a semi-structured guide were conducted in individuals with recent experience taking oral selexipag for PAH. Each interview included concept elicitation to gather participants’ perspectives on symptomatic AEs (type, frequency, severity, and interference) and cognitive debriefing of PRO-CTCAE items addressing the most frequently reported AEs of oral selexipag. Results Interviews were conducted with 20 participants with PAH (mean [range] age 50 [24–68] years; 75% female; 85% in World Health Organization Functional Class II–III), comprising different races/ethnicities, levels of education, and employment status. Fifteen participants were currently treated with selexipag; five had taken selexipag for ≥ 6 months before discontinuing. The most frequently reported AEs included headache, jaw pain, and nausea (n = 15, 12, and 10 participants, respectively). Diarrhea and headache were identified as the most bothersome AEs by 5 and 4 participants, respectively. Some AEs were transitory (e.g., jaw pain); others were long-lasting (e.g., muscle pain). Based on findings from Round 1 interviews, a flushing item was added and the PRO-CTCAE general pain item was modified to be specific to jaw pain for testing in Round 2. Interview findings identified the following AEs as relevant to assess in a PAH clinical trial: nausea, vomiting, diarrhea, flushing, jaw pain, headache, aching muscles, and aching joints. Conclusions The PRO-CTCAE items selected in this study and the additional symptomatic AEs identified as patient-relevant have the potential to be included in assessments capturing the patient perspective on tolerability in future studies of selexipag and possibly other PAH therapies