Spinal Cord Stimulation for Neuropathic Pain in England From 2010 to 2020: A Hospital Episode Statistics Analysis.

OBJECTIVES: Spinal cord stimulation (SCS) is a recognized intervention for the management of chronic neuropathic pain. The United Kingdom National Institute of Health and Care Excellence has recommended SCS as a management option for chronic neuropathic pain since 2008. The aim of this study is to undertake an assessment of SCS uptake across the National Health Service in England up to 2020. MATERIALS AND METHODS: Hospital Episode Statistics were obtained for patients with neuropathic pain potentially eligible for SCS and patients receiving an SCS-related procedure. Data were retrieved nationally and per region from the years 2010-2011 to 2019-2020. RESULTS: There were 50,288 adults in England attending secondary care with neuropathic pain in 2010-2011, increasing to 66,376 in 2019-2020. The number of patients with neuropathic pain with an SCS procedure increased on a year-to-year basis until 2018-2019. However, less than 1% of people with neuropathic pain received an SCS device with no evidence of an increase over time when considering the background increase in neuropathic pain prevalence. CONCLUSION: Only a small proportion of patients in England with neuropathic pain potentially eligible for SCS receives this intervention. The recommendation for routine use of SCS for management of neuropathic pain has not resulted in an uptake of SCS over the last decade.

Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BACKGROUND: Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. METHODS: In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 µg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. RESULTS: 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72-1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23-92 mL; p=0.002). Adverse events were similar under both treatments. CONCLUSIONS: Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Patient perspectives on symptoms, health-related quality of life, and treatment experience associated with relapsed/refractory multiple myeloma.

PURPOSE: This study aimed to better understand the patient perspective and treatment experience of relapsed and/or refractory multiple myeloma (RRMM). METHODS: This qualitative study enrolled adult RRMM patients from 6 US clinics who had ≥ 3 months of life expectancy, ≤ 6 prior lines of therapy, and ≥ 1 treatment regimen with a proteasome inhibitor and immunomodulator, or a CD38 monoclonal antibody or an alkylating agent, and a steroid. In-person semi-structured qualitative interviews were conducted to capture concepts that were relevant and important to patients. Topics included RRMM symptoms and impacts and the mode of administration, frequency, duration, convenience, side effects, and overall experience with RRMM treatment. RESULTS: A total of 22 patients completed interviews. At enrollment, 59.1% of participants were using regimens containing dexamethasone, 36.4% daratumumab, 27.3% carfilzomib, and 18.2% lenalidomide. More participants had experience using intravenous or injectable therapy alone (40.9%) than oral therapy alone (18.2%). Back pain and fatigue were the most frequently reported symptoms (40.9% each); 27.3% reported no symptoms. Most participants reported physical function limitations (86.4%), emotional impacts (77.3%), MM-related activity limitations (72.7%), and sleep disturbances (63.6%). Most participants perceived treatment effectiveness based on physician-explained clinical signs (68.2%) and symptom relief (40.9%). Participants experienced gastrointestinal adverse events (59.1%), fatigue (59.1%), sleep disturbances (31.8%), and allergic reactions (31.8%) with treatment. Key elements of treatment burden included the duration of a typical treatment day (68.2%), treatment interfering with daily activities (54.5%), and infusion duration (50.0%). CONCLUSIONS: These results provide treatment experience-related data to further understand RRMM treatment burden and better inform treatment decision-making.

To Trial or Not to Trial Before Spinal Cord Stimulation for Chronic Neuropathic Pain: The Patients' View From the TRIAL-STIM Randomized Controlled Trial.

Objectives Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine suitability for a permanent implant, its evidence base is limited. The recent TRIAL-STIM study (a randomized controlled trial at three centers in the United Kingdom) found no evidence that an SCS screening trial strategy provides superior patient outcomes as compared with a no trial approach. As part of the TRIAL-STIM study, we undertook a nested qualitative study to ascertain patients' preferences in relation to undergoing a screening trial or not. Materials and Methods We interviewed 31 patients sampled from all three centers and both study arms (screening trial/no trial) prior to SCS implantation, and 23 of these patients again following implantation (eight patients were lost to follow-up). Interviews were undertaken by telephone and audio-recorded, then transcripts were subject to thematic analysis. In addition, participants were asked to state their overall preference for a one-stage (no screening trial) versus two-stage (screening trial) implant procedure on a five-point Likert scale, before and after implantation. Results Emergent themes favoured the option for a one-stage SCS procedure. Themes identified include: saving time (off work, in hospital, attending appointments), avoiding the worry about having "loose wires" in the two-stage procedure, having only one period of recovery, and saving NHS resources. Participants' rated preferences show similar support for a one-stage procedure without a screening trial. Conclusions Our findings indicate an overwhelming preference among participants for a one-stage SCS procedure both before and after the implant, regardless of which procedure they had undergone. The qualitative study findings further support the TRIAL-STIM RCT results.

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM).

BACKGROUND: Therapy choices in relapsed/refractory multiple myeloma (RRMM) should consider patient satisfaction with treatment, because it is associated with adherence to therapy, health outcomes, and medical safety. The primary objective of this pilot cross-sectional observational study was to ascertain factors associated with patient-reported treatment satisfaction in RRMM. PATIENTS AND METHODS: Patients with a self-reported diagnosis of RRMM recruited from PatientsLikeMe, MyelomaCrowd, and Facebook were administered an electronic survey that included questions on demographics and clinical history, treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication, Eastern Cooperative Oncology Group performance status (ECOG PS) measure, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Univariable and multivariable analyses were used to identify predictors of patient-perceived treatment satisfaction. RESULTS: One hundred sixty patients with RRMM participated in the study, with a median of two prior relapses and 66.3% reporting the most recent relapse within the last 12 months. ECOG PS ≥2 was associated with lower patient-reported global satisfaction and perceived effectiveness of current treatment. In addition to shorter time spent receiving therapy, orally administered treatment was the strongest predictor of higher satisfaction with treatment convenience. For patients receiving an injectable drug-containing regimen versus an all-oral regimen, respectively, time spent receiving multiple myeloma-directed therapy was higher (12.6 vs. 4.0 hours per month), and total monthly indirect costs were $1,033 and $241. CONCLUSION: Poor ECOG PS was linked to reduced treatment satisfaction and perceived effectiveness of current therapy, whereas an all-oral regimen was associated with increased treatment convenience satisfaction. IMPLICATIONS FOR PRACTICE: This study suggests that attributes including better Eastern Cooperative Oncology Group performance status, less time spent receiving treatment, and oral route of treatment administration lead to higher patient-perceived satisfaction with relapsed/refractory multiple myeloma (RRMM) treatment. Oral route of administration was also associated with less time spent receiving treatment and reduced economic burden for patients. Increased attention to these factors in shared treatment decision making is warranted to help identify individual patient needs, preferences, and expectations for RRMM treatments, to resolve dissatisfaction issues, and to improve the experience of patients with RRMM.

Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA.

AIM: To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS: First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS: A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION: These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.

Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.

Use of the SF-36v2 Health Survey as a Screen for Risk of Major Depressive Disorder in a US Population-based Sample and Subgroup With Chronic Pain.

STUDY OBJECTIVES: To assess the feasibility of using the SF-36v2 mental health (MH) and mental component summary (MCS) scores for classification of risk for major depressive disorder (MDD), and to determine cut-off scores based on the sensitivity and specificity in a general US representative sample, and a chronic pain subpopulation. METHODS: Data were analyzed from the 2013 US National Health and Wellness Survey (adults 18 y old and above; N=75,000), and among a chronic pain subpopulation (n=6679). Risk of MDD was a score ≥10 on the Patient Health Questionnaire (PHQ-9). Logistic regression modeling was used to predict at risk for MDD and receiver operating characteristic curves were produced. RESULTS: The total sample had MH scores of 48.8 and MCS scores of 48.9, similar to the normative US population mean. Percent of respondents with a PHQ-9≥10 were 15.0% and 29.1% for the total sample and chronic pain subpopulation, respectively. Cut-off scores (PHQ-9≥10) in the total sample for the MH and MCS were 43.0 and 46.0, respectively. Specificities for the MH and MCS were 77.8% and 76.1%; sensitivities were 84.9% and 88.1%, respectively. Among the subpopulation with chronic pain, cut-off scores for the MH and MCS were 40.4 and 43.1, respectively. Corresponding specificities for the MH and MCS were 77.9% and 73.9%; sensitivities were 78.3% and 83.4%, respectively. CONCLUSIONS: The SF-36v2 was found to have sufficient specificity and sensitivity to categorize participants at risk for MDD. If no depression questionnaire is available, it is feasible to use the SF-36v2 to characterize the MH of populations.

Illustrating the impact of mild/moderate and severe haemophilia on health-related quality of life: hypothesised conceptual models.

INTRODUCTION/AIMS: Haemophilia and its treatment have a significant impact on patients' lives. The study objectives were to understand the impacts of haemophilia and its treatment from the patient perspective and to inform the development of comprehensive health-related quality-of-life (HRQL) conceptual models to illustrate these impacts. METHODS: The study included two phases. Phase I involved a review of literature published from 1995 to 2010, qualitative analysis of six patient (N = 31) and three healthcare provider (N = 15) focus group transcripts, and interviews with two experts to inform draft conceptual models of mild/moderate and severe haemophilia. Phase II involved interviews with 20 haemophilia patients and qualitative analysis of transcripts to confirm the concepts and structure of the conceptual models. RESULTS: The literature search resulted in 66 publications assessing HRQL, four of which were qualitative studies on the impact of haemophilia from the patient perspective. Results from Phase I indicated that acute bleeding events result in pain, swelling, bruising and restricted joint movement; repeated joint bleeds result in chronic symptoms, such as pain and arthropathy. Acute bleeds cause interruptions in daily activities and interfere with work/school. Patients have fears about having bleeds, which can affect their participation in activities, such as sports or crowded events. Patients also expressed feelings of depression, frustration, isolation and embarrassment. Results of Phase II corroborated findings from Phase I. CONCLUSIONS: The conceptual models illustrate the substantial impact of haemophilia and its treatments on patients' lives and can help inform clinical study design and the selection of endpoints to assess treatment benefit.

The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) by racial/ethnic group and age: results from OAB-POLL.

AIMS: To estimate the prevalence of LUTS and OAB in a large, ethnically diverse US study. METHODS: This cross-sectional, population-representative survey was conducted via the Internet in the US among 10,000 men and women aged 18-70 (2,000 African-Americans [AA], 2,000 Hispanics, 6,000 whites). The LUTS tool assessed how often participants experienced LUTS during the past 4 weeks on a five-point Likert scale. OAB was defined by the presence of urinary urgency ≥ "sometimes" or ≥ "often," and/or the presence of urgency urinary incontinence (UUI). Descriptive statistics were used to evaluate group differences. Logistic regression analyses were conducted to examine the impact of racial/ethnic group on OAB. RESULTS: Response rate, 56.7%. Prevalent LUTS included terminal dribble and nocturia across gender, post-micturition leaking (men), and stress incontinence (women). Prevalence of OAB ≥ "sometimes" and ≥ "often" were 17% and 8% in men and 30% and 20% in women--with significantly higher rates among AA men and women. A similar trend was found for UUI among men (AA, 10%; Hispanic and whites, 6%), while AA and white women had higher prevalence of UUI (19%) as compared to Hispanic women (16%). In logistic regression analyses, AA and Hispanic men and women were significantly more likely than whites to have OAB despite having lower prevalence of self-reported comorbid conditions and risk factors. CONCLUSIONS: LUTS and OAB are highly prevalent in both men and women and increase with advancing age. Further, racial/ethnic group is a robust predictor of OAB in men and women.

Identifying symptomatic adverse events using the patient-reported outcomes version of the common terminology criteria for adverse events in patients with non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations.

OBJECTIVE: Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient-reported symptomatic adverse events (AEs) to measure in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. METHODS: This study selected relevant symptomatic AEs from 78 AEs available in the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews. RESULTS: During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25-item PRO-CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO-CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience. CONCLUSIONS: The 25-item PRO-CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision-making for patients, caregivers, healthcare providers, and regulators.

Does a Screening Trial for Spinal Cord Stimulation in Patients With Chronic Pain of Neuropathic Origin Have Clinical Utility (TRIAL-STIM)? 36-Month Results From a Randomized Controlled Trial.

BACKGROUND: Screening trials before full implantation of a spinal cord stimulation device are recommended by clinical guidelines and regulators, although there is limited evidence for their use. The TRIAL-STIM study showed that a screening trial strategy does not provide superior patient pain outcome at 6-month follow-up compared with not doing a screening trial and that it was not cost-effective. OBJECTIVE: To report the long-term follow-up results of the TRIAL-STIM study. METHODS: The primary outcome of this pragmatic randomized controlled trial was pain intensity as measured on a numerical rating scale (NRS) and secondary outcomes were the proportion of patients achieving at least 50% and 30% pain relief at 6 months, health-related quality of life, and complication rates. RESULTS: Thirty patients allocated to the "Trial Group" (TG) and 36 patients allocated to the "No Trial Group" (NTG) completed outcome assessment at 36-month follow-up. Although there was a reduction in NRS pain and improvements in utility scores from baseline to 36 months in both groups, there was no difference in the primary outcome of pain intensity NRS between TG and NTG (adjusted mean difference: -0.60, 95% CI: -1.83 to 0.63), EuroQol-5 Dimension utility values (adjusted mean difference: -0.02, 95% CI: -0.13 to 0.10), or proportion of pain responders (33% TG vs 31% NTG). No differences were observed between the groups for the likelihood of spinal cord stimulation device explant or reporting an adverse advent up to 36-month follow-up. CONCLUSION: The long-term results show no patient outcome benefit in undertaking an SCS screening trial.

Q-TWiST analysis of ixabepilone in combination with capecitabine on quality of life in patients with metastatic breast cancer.

BACKGROUND: Combination therapy with ixabepilone and capecitabine (cape) is approved for use in patients with locally advanced/metastatic breast cancer that is resistant to treatment with anthracyclines or taxanes. The current study evaluated the trade-off between quality and quantity of life using quality-adjusted time without symptoms or toxicity (Q-TWiST) outcomes. METHODS: Within the trial, 752 women were randomly assigned to receive either the combination of ixabepilone and cape (once every 21 days) or cape alone (on days 1-14). The area under the survival curve was partitioned into 3 health states: toxicity (TOX), time without symptoms of disease progression or toxicity, and recurrence (relapse [REL]). The mean time in each health state was weighted by a range of utilities and summed to estimate quality-adjusted survival (QAS). Patient-reported outcomes were also evaluated using the Functional Assessment of Cancer Therapy (FACT)-Breast Symptom Index (FBSI). RESULTS: A statistically significant difference between groups with regard to change from baseline FBSI scores favoring the cape group was observed (P = .0002), but no differences were observed after adjusting for deaths in the analysis. All combinations of utilities for REL and TOX resulted in an observed difference in QAS favoring combination therapy. Differences were found to be statistically significant for comparisons, with higher tolerance for TOX. QAS was found to be greater for the combination therapy group (42.2 weeks vs 38.4 weeks), assuming the base case scenario of utility equal to 0.5 for both TOX and REL (P = .0227). CONCLUSIONS: The Q-TWiST analysis supports a positive benefit-risk ratio for the combination of ixabepilone plus cape in patients with advanced/metastatic breast cancer that is refractory to anthracyclines and taxanes versus cape alone, despite the potential for added toxicities with combination therapy.

What do we know about asthma triggers? a review of the literature.

OBJECTIVE: For patients with asthma, exacerbations and poor control can result from exposure to environmental triggers, such as allergens and air particulates. This study reviewed the international literature to determine whether a global checklist of common asthma triggers might be feasible for use as a research or management tool in clinical practice. METHODS: Literature published from 2002 to 2012 was identified through PubMed and EMBASE using the following search terms: asthma, asthma triggers, prevalence, among others. A total of 1046 abstracts were found; 85 articles were reviewed covering six continents (number of articles): Africa (1), Asia (22), Australia (1), Europe (27), North America (22), and South America (4). RESULTS: The literature consistently pointed to asthma triggers as one contributor to poor asthma control. Frequently cited triggers were similar across countries/regions and included allergens (particularly pollens, molds, dust, and pet dander), tobacco smoke, exercise, air pollutants/particulates, weather patterns/changes, and respiratory infections. Definitions of asthma triggers, how triggers are taken into account in definitions of asthma control, and scientific inquiry into optimal management techniques for triggers were inconsistent and sparse. CONCLUSIONS: Given the apparent importance of triggers in attaining and maintaining asthma control, empirical research concerning optimal trigger management is needed. Results demonstrate that asthma triggers are similar across continents, suggesting a global checklist of triggers for use in research and clinical practice would be feasible.

Screening trials of spinal cord stimulation for neuropathic pain in England-A budget impact analysis.

Screening trials of spinal cord stimulation (SCS) prior to full implantation of a device are recommended by expert guidelines and international regulators. The current study sought to estimate the budget impact of a screening trial of SCS and the costs or savings of discontinuing the use of a screening trial. A budget impact analysis was performed considering a study population that reflects the size and characteristics of a patient population with neuropathic pain in England eligible for SCS. The perspective adopted was that of the NHS with a 5-year time horizon. The base case analysis indicate that a no screening trial strategy would result in cost-savings to the NHS England of £400,000-£500,000 per year. Sensitivity analyses were conducted to evaluate different scenarios. If ≥5% of the eligible neuropathic pain population received a SCS device, cost-savings would be >£2.5 million/year. In contrast, at the lowest assumed cost of a screening trial (£1,950/patient), a screening trial prior to SCS implantation would be cost-saving. The proportion of patients having an unsuccessful screening trial would have to be ≥14.4% for current practice of a screening trial to be cost-saving. The findings from this budget impact analysis support the results of a recent UK multicenter randomized controlled trial (TRIAL-STIM) of a policy for the discontinuation of compulsory SCS screening trials, namely that such a policy would result in considerable cost-savings to healthcare systems.

Measuring patient-reported physical functioning and fatigue in myelodysplastic syndromes using a modular approach based on EORTC QLQ-C30.

PURPOSE: Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library. METHODS: The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated. RESULTS: The QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe). CONCLUSION: The modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML.

SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials.

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.

Metabolic profiling of muscle contraction in lean compared with obese rodents.

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs. Predictably, IMTG content was grossly elevated in control muscles from obese rats compared with their lean counterparts. In muscles of obese (but not lean) rats, contraction resulted in marked hydrolysis of IMTG, which was then restored to near resting levels during 25 min of recovery. Despite dramatic phenotypical differences in contraction-induced IMTG turnover, muscle levels of diacylglycerol (DAG) and long-chain acyl-CoAs (LCACoA) were surprisingly similar between groups. Tissue profiles of acylcarnitine metabolites suggested that the surfeit of IMTG in obese rats fueled higher rates of fat oxidation relative to the lean group. Muscles of the obese rats had reduced lactate levels immediately following contraction and higher glycogen resynthesis during recovery, consistent with a lipid-associated glucose-sparing effect. Together, these findings suggest that contraction-induced mobilization of local lipid reserves in obese muscles promotes beta-oxidation, while discouraging glucose utilization. Further studies are necessary to determine whether persistent oxidation of IMTG-derived fatty acids contributes to systemic glucose intolerance in other physiological settings.

The Improved Health Outcomes Program (iHOP): A Unique Model to Promote Provider-Driven Research in a Medicaid Population.

We describe an effort to improve the care of Medicaid and uninsured individuals through a three-way partnership between a Medicaid managed care insurer, front-line providers, and an academic university. The project provided annual funding over eleven years, for research, pilot programs, and demonstration projects. Projects were provider-driven in design and methods. The Medicaid-managed care insurer-funded proposals were vetted by a neutral university team experienced in grant writing and community-based research and scored by a community-based review panel. The grant program ran from 2007 to 2018, funding 41 projects, totaling USD 2,097,842. The partnership of an insurer, a university, and frontline providers was not only viable and sustainable for over a decade, but also flexible, free of project selection issues, and well-received by all stakeholders. Funded providers worked in both urban and rural settings and included hospitals, community non-profits, outpatient clinics, academic and community health partnerships, and public health agencies. The projects generally reflected common issues in the Medicaid and uninsured population needs, such as childhood obesity, and they were consistent with the targeted goals of the program. Broad health foci included child and/or maternal health, chronic conditions, mental health, preventive health, screening, system effectiveness, special populations including refugees, Latinos, and rural individuals, and substance use disorders. Details of the awarded grantee goals, the grants management process, and lessons learned from the partnership are presented. The partnership triad model was effective and stable, with each partner adding unique value. The use of the academic institution to administrate the program provided an arms-length relationship between the insurer and the providers in project selection and allowed assistance to less experienced researchers in community settings.

Treatment Satisfaction and Burden of Illness in Patients with Newly Diagnosed Multiple Myeloma.

OBJECTIVES: This observational study identified attributes of patient-reported satisfaction with therapy for multiple myeloma (MM), described the treatment-related time burden and indirect costs, and investigated the effect of administration route (oral vs. injectable) on these outcomes among patients with newly diagnosed MM (NDMM) and among caregivers. METHODS: Patients residing in the USA with a self-reported diagnosis of NDMM were recruited from PatientsLikeMe, MyelomaCrowd, and Facebook (16 December 2016 and 6 July 2017) to complete an electronic survey including questions on treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication with three domains (global satisfaction, effectiveness, and convenience) and the Work Productivity and Activity Impairment Questionnaire. Univariate and multivariate analyses identified predictors of patient-perceived treatment satisfaction. RESULTS: Among 188 patients, worse Eastern Cooperative Oncology Group performance status (ECOG PS) was correlated with lower patient-perceived effectiveness and convenience of their current treatment. White race and oral administration route were independently correlated with higher patient-perceived convenience of treatment. Injectable therapy use was associated with a trend towards increased activity impairment (43 vs. 34%; p = 0.05) and significantly higher time burden of treatment administration, with threefold higher adjusted indirect costs of MM therapy compared with solely orally administered therapies (monthly mean $US482 vs. 153; 2016 values; p < 0.0001). CONCLUSIONS: Factors associated with patient-perceived satisfaction with NDMM treatment-ECOG PS, race, administration route-warrant increased attention in shared treatment decision making to help identify patient needs and improve the patient's treatment experience. The use of orally administered therapies could improve patients' activity impairment and reduce the time burden associated with therapy.