Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109: Secondary Analysis of a Randomized Clinical Trial.

Importance: Recurrent Clostridioides difficile infection (CDI) is a debilitating disease leading to poor health-related quality of life (HRQOL), loss of productivity, anxiety, and depression. The potential association of treatment with HRQOL has not been well evaluated. Objectives: To explore the association of SER-109 compared with placebo on HRQOL in patients with recurrent CDI up to week 8. Design, Setting, and Participants: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial that took place at 56 sites in the US and Canada from July 2017 to April 2020 and included 182 patients randomized to SER-109 or placebo groups. Interventions: SER-109 or placebo (4 capsules once daily for 3 days) following antibiotics for CDI. Main Outcomes and Measures: Exploratory analysis of HRQOL using the disease specific Clostridioides difficile Quality of Life Survey (Cdiff32) assessed at baseline, week 1, and week 8. Results: In this study, 182 patients (109 [59.9%] female; mean age, 65.5 [16.5] years) were randomized to SER-109 (89 [48.9%]) or placebo (93 [51.1%]) groups and were included in the primary and exploratory analyses. Baseline Cdiff32 scores were similar between patients in the SER-109 and placebo groups (52.0 [18.3] vs 52.8 [18.7], respectively). The proportion of patients with overall improvement from baseline in the Cdiff32 total score was higher in the SER-109 arm than placebo at week 1 (49.4% vs 26.9%; P = .012) and week 8 (66.3% vs 48.4%; P = .001).Greater improvements in total and physical domain and subdomain scores were observed in patients in the SER-109 group compared with placebo as early as week 1, with continued improvements observed at week 8. Among patients in the placebo group, improvements in HRQOL were primarily observed in patients with nonrecurrent CDI while patients in the SER-109 group reported improvements in HRQOL, regardless of clinical outcome. Conclusions and Relevance: In this secondary analysis of a phase 3 clinical trial, SER-109, an investigational microbiome therapeutic was associated with rapid and steady improvement in HRQOL compared with placebo through 8 weeks, an important patient-reported outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03183128.

Validation of a Health-Related Quality of Life Questionnaire in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Phase 3 Randomized Trial.

BACKGROUND: Debilitating symptoms of recurrent Clostridioides difficile infection (rCDI) often lead to long-term effects on health-related quality-of-life (HRQOL). In ECOSPOR III, SER-109, an investigational oral microbiome therapeutic, was superior to placebo in reducing rCDI. We investigated the validity, reliability, and responsiveness of a 32-item, CDI-specific questionnaire-the Clostridium difficile Quality of Life Survey (Cdiff32)-across mental, physical, and social domains in patients with rCDI. METHODS: In this post hoc analysis of a phase 3 clinical trial, 182 outpatients with rCDI completed Cdiff32 and EQ-5D at baseline and at 1 and 8 weeks. Cdiff32 was evaluated for item performance, internal reliability, and convergent validity. To assess known-groups validity, Cdiff32 scores were compared by disease recurrence status at week 1; internal responsiveness was evaluated in the nonrecurrent disease group by 8 weeks by means of paired t test. RESULTS: All 182 patients (mean age [standard deviation], 65.5 [16.5] years; 59.9% female) completed baseline Cdiff32. Confirmatory factor analysis identified 3 domains (physical, mental, and social relationships) with good item fit. High internal reliability was demonstrated (Cronbach α = 0.94 with all subscales >0.80). Convergent validity was evidenced by significant correlations between Cdiff32 subscales and EQ-5D (r = 0.29-0.37; P < .001). Cdiff32 differentiated patients by disease recurrence status at week 1 (effect sizes, 0.38-0.42; P < .05 overall), with significant improvement from baseline through week 8 in patients with nonrecurrent disease at week 1 (effect sizes, 0.75-1.02; P < .001 overall). CONCLUSIONS: Cdiff32 is a valid, reliable, and responsive disease-specific HRQOL questionnaire that is fit for purpose for interventional treatment trials. The significant improvement in patients with nonrecurrent disease by 8 weeks demonstrates the negative impact of rCDI on HRQOL.

Feasibility of an online mindfulness program for stress management--a randomized, controlled trial.

BACKGROUND: Chronic stress affects many Americans. Stress management programs may be prohibitively expensive or have limited access. PURPOSE: This study aims to determine feasibility of an 8-week Internet-based stress management program (ISM) based on mindfulness principles in reducing stress in a 12-week, parallel, randomized, controlled trial. METHODS: Participants were randomly allocated to ISM, ISM plus online message board (ISM+), or control groups. Perceived stress, mindfulness, self-transcendence, psychological well-being, vitality, and quality of life were measured at baseline, week 8, and week 12 using standard validated questionnaires. RESULTS: ISM and ISM+ groups demonstrated statistically significant improvements compared with control on all measures except vitality and physical health. CONCLUSIONS: The ISM program effectively and sustainably reduced measures of stress. The magnitude of improvement is comparable to traditional mindfulness programs, although fewer participants were engaged. This feasibility study provides strong support for online stress management programs, which increase access at a fraction of cost of traditional programs.

Asthma patients prefer Respimat Soft Mist Inhaler to Turbuhaler.

Device satisfaction and preference are important patient-reported outcomes to consider when choosing inhaled therapy. A subset of adults (n = 153) with moderate or severe asthma participating in a randomized parallel-group, double-dummy trial that compared the efficacy and safety of 12 weeks' treatment with budesonide delivered via Respimat Soft Mist Inhaler (SMI) (200 or 400 microg bd) or Turbuhaler dry powder inhaler (400 microg bd), completed a questionnaire on patient device preference and satisfaction (PASAPQ) as part of a psychometric validation. As the study used a double-dummy design to maintain blinding, patients used and assessed both devices, rating their satisfaction with, preference for, and willingness to continue using each device. The mean age of patients was 41 years, 69% were female and the mean duration of disease was 16 years. Total PASAPQ satisfaction scores were 85.5 and 76.9 for Respimat SMI and Turbuhaler respectively (p < 0.0001); 112 patients (74%) preferred Respimat SMI and 26 (17%) preferred Turbuhaler. Fourteen subjects (9%) indicated no preference for either inhaler. Willingness to continue using Respimat SMI was higher than that for Turbuhaler (mean scores: 80/100 and 62/100, respectively). Respimat SMI was preferred to Turbuhaler by adult asthma patients who used both devices in a clinical trial setting.

Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence.

OBJECTIVE: To evaluate the impact of botulinum toxin type A (BoNTA) on health-related quality of life in patients with neurogenic urinary incontinence (UI) using the Incontinence Quality of Life questionnaire (I-QOL). METHODS: Randomized, double-blind, multicenter, placebo-controlled study involving eight centers across Belgium, France, and Switzerland. Patients (n = 59) with UI due to neurogenic detrusor overactivity (spinal cord injury, n = 53; multiple sclerosis, n = 6) who were inadequately managed on oral anticholinergics received a single dose of BoNTA (200U or 300U, Botox) or placebo. I-QOL scores at screening and after treatment at weeks 2, 6, 12, 18, and 24 were recorded. RESULTS: Median total and subscale I-QOL scores increased significantly from screening with BoNTA 300U compared with placebo at all time points (p<0.05) and with BoNTA 200U compared with placebo at all time points for total score and the Avoidance Limiting Behavior subscale (p<0.05), and at weeks 2, 6, 12, and 18 (p<0.05), but not 24 for the Psychosocial Impact and Social Embarrassment subscales. Approximately twice as many BoNTA recipients as placebo recipients achieved at least a minimal important difference in total I-QOL score at 2, 6, 12, and 24 wk. CONCLUSIONS: BoNTA significantly improves UI-associated health-related quality of life in patients with neurogenic UI.

Reliability and validity of the Incontinence Quality of Life questionnaire in patients with neurogenic urinary incontinence.

OBJECTIVE: To assess the reliability, validity, responsiveness, and minimally important difference (MID) of the Incontinence Quality of Life (I-QOL) questionnaire in patients with urinary incontinence due to neurogenic detrusor overactivity. DESIGN: Randomized, double-blind, multicenter, placebo-controlled study. SETTING: Eight centers across Belgium, France, and Switzerland. PARTICIPANTS: Patients with urinary incontinence due to neurogenic detrusor overactivity inadequately managed on oral anticholinergics. Fifty-nine patients (spinal cord injury, n=53; multiple sclerosis, n=6) were enrolled. INTERVENTION: Single dose of botulinum toxin type A (Botox) (200 or 300 U) or placebo. MAIN OUTCOME MEASURES: I-QOL questionnaire completed at screening and over a 24-week post-treatment period. RESULTS: The Cronbach alpha ranged from .79 to .93, indicating that I-QOL is a reliable measure of QOL in neurogenic urinary incontinence patients. No item had more than 5.1% missing or out of range values. With the exception of 2 items, questions showed acceptable item-scale correlation and scaling success results varied by domain. Post-treatment correlations indicated acceptable construct validity. The I-QOL was responsive to improvements in symptoms. MID values ranged from 4 to 11 points. CONCLUSIONS: Results suggest that I-QOL is a reliable, valid, and responsive measure of incontinence-related QOL in neurogenic patients.

The validation of patient-rated global assessments of treatment benefit, satisfaction, and willingness to continue--the BSW.

OBJECTIVE: This study evaluated the validity of three single-item, patient-rated, interviewer-administered, global assessments of treatment benefit, satisfaction with treatment and willingness to continue treatment, collectively referred to as the BSW. METHODS: The BSW, micturition diaries, the Overactive Bladder Questionnaire (OAB-q) and the King's Health Questionnaire (KHQ) were included in part or in total in three OAB clinical trials. Discriminant validity for full and dichotomized responses was assessed with anovas models and correlations were used to evaluate construct validity. RESULTS: The BSW demonstrated significant differences among the majority of the response levels on all measures of micturitions in all studies. The BSW also demonstrated discriminant validity with the OAB-q and the KHQ. BSW measures demonstrated significant differences among the change scores for all subscales of the OAB-q and the majority of the KHQ domains with both full and dichotomized responses. Patients who were dissatisfied with treatment and those unwilling to continue treatment also reported significantly worse OAB-q and KHQ scores compared with those who were satisfied with treatment or willing to continue treatment. BSW measures were moderately correlated with the micturition variables, moderate to strongly correlated with the OAB-q and weak to moderately with the KHQ, providing support for the construct validity of the BSW measures. CONCLUSIONS: The BSW is a useful tool to capture patients' global impressions of three key elements of treatment outcome: a perceived benefit, satisfaction with treatment, and the willingness to continue treatment, and can facilitate patient-physician communication as well as be informative to researchers.

How much is enough and who says so?

BACKGROUND: One of the challenges of health-related quality of life research is to translate statistically significant health-related quality of life changes into interpretable clinical or medically important ones. OBJECTIVE: To calculate the minimal important difference of the King's Health Questionnaire, a condition-specific health-related quality of life questionnaire for the assessment of men and women with lower urinary tract dysfunction. METHODS: The King's Health Questionnaire was administered to patients suffering from overactive bladder enrolled in two multinational studies. Minimal important differences were calculated using an anchor-based approach with both a global rating of patient-perceived treatment benefit and one of perceived disease impact. A distribution-based method using effect size was calculated for comparison purposes. RESULTS: Minimal important difference values varied slightly with each method. Using the anchor-based approach, the King's Health Questionnaire minimal important difference ranged between 5-10 points when the calculation factored out patients who reported no change and 6-12 points for patients who experienced a small improvement. The effect size method indicated a minimal important difference of 5 to 6 points for a small effect and 10 to 15 points for a medium effect. CONCLUSIONS: In the case of the King's Health Questionnaire, the anchor-based approaches and the distribution-based approach provide similar results. A change from baseline of at least 5 points on King's Health Questionnaire domains indicates a change that is meaningful to patients and is indicative of a clinically meaningful improvement in health-related quality of life after treatment. Convergence of the estimates using different approaches should give us confidence in the values derived for the quality of life domains measured by the King's Health Questionnaire.

Multinational study of reliability and validity of the King's Health Questionnaire in patients with overactive bladder.

OBJECTIVE: Overactive bladder (OAB) has substantial impact on health-related quality of life (HRQoL). The purpose of this research was to evaluate the psychometric properties of the King's Health Questionnaire (KHQ). METHODS: The KHQ (n = 1284) was administered at baseline and 12 weeks post-treatment in a multinational, double-blind, randomized clinical trial of tolterodine for treatment of OAB. Country-specific psychometric analyses of HRQoL instruments were performed. Countries demonstrating marginal psychometric properties on the KHQ were pooled with same-language countries, re-evaluated, and aggregate analysis performed on the pooled data. RESULTS: Internal consistency of the KHQ was high, item characteristics were good, most assumptions of summed scales were met, and it is externally valid and consistent. Few problems with the KHQ were noted although the performance of the personal relationships domain was complicated by the 'not applicable' response category. CONCLUSIONS: Psychometric testing supports the reliability and validity of the KHQ as an OAB-specific measure of HRQoL.

Screening, prevention and socioeconomic costs associated with the treatment of colorectal cancer.

Colorectal cancer (CRC), the third most prevalent cancer worldwide, imposes a significant economic and humanistic burden on patients and society. One study conservatively estimated the annual expenditures for colorectal cancer to be approximately dollars US 5.3 billion in 2000, including both direct and indirect costs. However, other investigators estimated inpatient costs alone incurred in the US in 1994 to be around dollars US 5.14 billion. Therefore, the economic burden of colorectal cancer in the US could be projected to be somewhere in the range of dollars US 5.5-6.5 billion by considering that inpatient costs approximate 80% of total direct costs. No worldwide data have been published, but assuming that the US represents 25-40% of total expenditures in oncology, as seen for breast and lung cancers, a rough estimate for colorectal cancer would be in the range of dollars US 14-22 billion. Screening helps increase patient survival by diagnosing colorectal cancer early. The ideal method among the four tests most used (faecal occult blood test, flexible sigmoidoscopy, colonoscopy and double contrast barium enema) has not been identified. Economic studies of colorectal cancer screening are complex because of the many variables involved, as well as the fact that the outcomes must be followed for many years, and the lack of consensus on screening guidelines. Intuitively, modelling colorectal cancer is one way to overcome these hurdles; published modelling studies predict colorectal cancer screening programs to be within the threshold of dollars US 40000 per life-year saved. The faecal occult blood test appears to be the only clearly effective test, both from a clinical and an economic viewpoint. Important limitations are the invasiveness and inconvenience of the screening procedures, except faecal occult blood test. Patients' comfort and satisfaction are essential in improving compliance with screening recommendations, which appears to be low even in the US (35% of the general population aged over 40 years and 60% of the high-risk population), the country with the highest awareness and compliance in the world. Since colorectal cancer is generally a disease of the elderly, its economic burden is expected to grow in the near future, mainly due to population aging. Potential avenues to pursue in order to contain or reduce the economic burden of colorectal cancer would be the design and implementation of efficient screening programmes, the improvement of patient awareness and compliance with screening guidelines, the development of appropriate prevention programs (i.e. primary and secondary), and earlier diagnosis.

The economic impact of opioids on postoperative pain management.

STUDY OBJECTIVE: To evaluate the consequences of opioid use for postoperative pain management and the degree to which these consequences may be reduced or minimized with opioid-sparing or opioid-replacement techniques. DESIGN: Literature review relating to the economics of postoperative pain management. Comparisons between opioids and opioid-sparing techniques were identified and selected for study. MEASUREMENTS AND MAIN RESULTS: Studies evaluating overall economic impacts or surrogate outcomes (e.g., resource use or recovery milestones) showed benefits with opioid-sparing therapies. CONCLUSIONS: Opioids will likely remain an integral part of postoperative pain management, but side effects increase the costs of care. The challenge is to identify situations where opioid-sparing techniques improve surrogate economic measurements and decrease overall hospital costs.

Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of overactive bladder (OAB) patients foilowing treatment with tolterodine extended-release (ER) 4 mg once daily versus placebo. STUDY DESIGN: Multinational, placebo-controlled, randomized, double-blind 12-week study. POPULATION: Patients with urinary frequency ( > or = 8 micturitions/24 hours over a 7-day period), urge incontinence ( > or = 5 episodes/week), and symptoms of OAB for at least 6 months were eligible for inclusion. Patients (81% female) received oral therapy with tolterodine ER (n = 507) or placebo (n = 508) for 12 weeks. OUTCOMES MEASURED: HRQoL was assessed using the King's Health Questionnaire (KHQ) and Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Patients also rated their bladder condition. Assessments were performed at baseline and at the end of treatment. RESULTS: At end of treatment, KHQ domains selected a priori as primary HRQoL end points (incontinence impact and role limitations) significantly improved (P < or = .001) with tolterodine ER. Domains selected a priori as secondary end points (physical limitations, sleep and energy, severity [coping] measures, and symptom severity) were also significantly improved (P < or = .006) following treatment with tolterodine ER. The tolterodine ER group had decreased symptom severity and statistically significant improvements in patient rating of bladder control compared with the placebo group at end of treatment. No treatment differences were detected using the SF-36. CONCLUSION: Many aspects of HRQoL, as measured by the KHQ, showed statistically significant improvement following treatment with tolterodine ER. These HRQoL improvements were consistent with clinical efficacy benefits. Patients receiving tolterodine ER experienced overall improvement in their condition that was associated with an important impact on their HRQoL.

Long-term health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To evaluate the long-term effects of tolterodine on the health-related quality of life (HRQoL) of patients diagnosed with overactive bladder with incontinence. METHODS: Patients who completed a 12-week randomized, double-blind, safety and efficacy trial comparing tolterodine with placebo were invited to enroll in a 12-month open-label continuation trial to assess the long-term safety and efficacy of tolterodine. This study reports the HRQoL results from the King's Health Questionnaire (KHQ) and the Short Form-36 (SF-36) that were administered at baseline, at the end of the 12-week trial, and 3 and 12 months following open-label treatment with tolterodine. RESULTS: One thousand seventy-seven patients were included in the intent-to-treat (ITT(B)) population. KHQ translations were available for 838 patients (mean age, 61.1 years; 80.9% women) in the ITT(B) population. HRQoL, as measured by the KHQ, significantly improved from baseline to months 3 and 12 on the following domains: incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep and energy, severity (coping) measures, and symptom severity. Improvements were generally consistent across all analyses for the 3- and 12-month measurements and for the ITT(B) and completer (C(B)) populations. Patients receiving tolterodine in the double-blind study showed additional improvement at the 3-month open-label assessment on all but the general health domain. At 12 months from treatment rollover, all improvements from rollover to 3 months were sustained with additional improvement seen on the incontinence impact and role limitations domains. The general health perceptions domain showed a slight decline from rollover that might be attributable to a natural decline in patients' health status at this life stage. These findings were consistent with other efficacy results whereby efficacy was maintained over the 12-month open-label period. SF-36 results were consistent with previous experience of reduced sensitivity, as population groups were similar to the SF-36 Physical Component and Mental Component scores at various time points and with all populations. CONCLUSION: Continued treatment with tolterodine provides additional benefits in HRQoL as measured by the KHQ. Of particular importance are improvements on the psychological aspects after longer-term treatment not detected after a short-term trial. Treatment effects on HRQoL are evident even after a 12-week placebo run-in supporting the true clinical effect of active treatment.