ENhANCE trial protocol: A multi-centre, randomised, phase IV trial comparing the efficacy of oxycodone/naloxone prolonged release (OXN PR) versus oxycodone prolonged release (Oxy PR) tablets in patients with advanced cancer.

Background: Oxycodone is a frequently used opioid in cancer. Opioid-induced constipation (OIC) is common. Oxycodone/Naloxone Prolonged Release (OXN PR) contains naloxone, which mitigates OIC. Trials have either focused on non-cancer pain, or conducted before significant experience of using OXN PR. This trial aims to: demonstrate (1) analgesic equivalence between OXN PR and Oxycodone Prolonged Release (Oxy PR), and (2) superiority of constipation outcomes in OXN PR compared to Oxy PR in cancer pain. Unlike other trials, it will only include patients with at least moderate pain scores (≥4/10), allow usual laxatives, and exclude potential liver dysfunction. Methods: This is a multi-centre, open-label, randomised, phase IV study of OXN PR vs Oxy PR in patients with cancer-related pain. The primary outcome is pain difference on Brief Pain Inventory-Short Form (BPI-SF) at 5 weeks. Secondary outcomes are comparison of other pain outcomes (BPI-SF) and neuropathic pain measures (Leeds Assessment of Neuropathic Symptoms & Signs (S-LANNS)), constipation (Bowel Function Index (BFI)), quality of life (EORTC-QLQ-C30), rescue analgesia use, total opioid dose, and total laxative dose over 5 weeks. Conclusion: The comparison of analgesic efficacy between both arms, and superiority of constipation in the OXN PR arm will add new knowledge on the comparisons of both agents, and oxycodone independently. This trial will extend knowledge of the effectiveness, safety, and adverse effect profiles of both drugs in terms of pain, constipation, quality of life outcomes for patients with cancer pain, and provide clinicians with high quality data to guide decision making. Trial registration: Name of the registry: ANZCTR. Trial registration number: ACTRN12619001282178. Date of registration: 17/09/2019. URL of trial registry record: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377673&isReview=trueProtocol version 2.1_28 August 2020.

Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis.

Background & Aims: The safety, tolerability, and efficacy of the non-bile acid farnesoid X receptor agonist tropifexor were evaluated in a phase II, double-blind, placebo-controlled study as potential second-line therapy for patients with primary biliary cholangitis (PBC) with an inadequate ursodeoxycholic acid response. Methods: Patients were randomised (2:1) to receive tropifexor (30, 60, 90, or 150 µg) or matched placebo orally once daily for 28 days, with follow-up on Days 56 and 84. Primary endpoints were safety and tolerability of tropifexor and reduction in levels of γ-glutamyl transferase (GGT) and other liver biomarkers. Other objectives included patient-reported outcome measures using the PBC-40 quality-of-life (QoL) and visual analogue scale scores and tropifexor pharmacokinetics. Results: Of 61 enrolled patients, 11, 9, 12, and 8 received 30-, 60-, 90-, and 150-µg tropifexor, respectively, and 21 received placebo; 3 patients discontinued treatment because of adverse events (AEs) in the 150-µg tropifexor group. Pruritus was the most frequent AE in the study (52.5% [tropifexor] vs. 28.6% [placebo]), with most events of mild to moderate severity. Decreases seen in LDL-, HDL-, and total-cholesterol levels at 60-, 90-, and 150 µg doses stabilised after treatment discontinuation. By Day 28, tropifexor caused 26-72% reduction in GGT from baseline at 30- to 150-µg doses (p <0.001 at 60-, 90-, and 150-µg tropifexor vs. placebo). Day 28 QoL scores were comparable between the placebo and tropifexor groups. A dose-dependent increase in plasma tropifexor concentration was observed, with 5- to 5.55-fold increases in AUC0-8h and Cmax between 30- and 150-µg doses. Conclusions: Tropifexor showed improvement in cholestatic markers relative to placebo, predictable pharmacokinetics, and an acceptable safety-tolerability profile, thereby supporting its potential further clinical development for PBC. Lay summary: The bile acid ursodeoxycholic acid (UDCA) is the standard-of-care therapy for primary biliary cholangitis (PBC), but approximately 40% of patients have an inadequate response to this therapy. Tropifexor is a highly potent non-bile acid agonist of the farnesoid X receptor that is under clinical development for various chronic liver diseases. In the current study, in patients with an inadequate response to UDCA, tropifexor was found to be safe and well tolerated, with improved levels of markers of bile duct injury at very low (microgram) doses. Itch of mild to moderate severity was observed in all groups including placebo but was more frequent at the highest tropifexor dose. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT02516605).

The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes.

Background & Aims: Non-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients' health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research. Methods: Medline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH. Results: Twenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients' ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated 'moderate' at quality assessment, and all evaluable studies had inadequate control of confounders. Conclusions: NASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes. Lay summary: Non-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals' relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.

Itch as a critical factor in impaired health-related quality of life in patients with plaque psoriasis achieving clear or almost-clear skin: Analysis of the single-arm, open-label, multicenter, prospective ProLOGUE study.

Background: Patients with psoriasis report impaired health-related quality of life (HRQoL; Dermatology Life Quality Index score ≥ 2) even after achieving clear or almost-clear skin with biologic treatment. Objective: To assess the effectiveness of brodalumab in HRQoL improvement and the factors associated with incomplete HRQoL improvement in Japanese patients with psoriasis. Methods: As a part of the single-arm, open-label, multicenter, prospective ProLOGUE study (Japan Registry of Clinical Trials identifier: jRCTs031180037), patients were treated with 210 mg of subcutaneous brodalumab in daily clinical practice until week 48. The absolute Psoriasis Area and Severity Index scores and patient-reported outcomes were assessed at baseline and weeks 12 and 48. Results: Seventy-three patients (male, 82.2%; median age, 54.0 years) were enrolled. The Dermatology Life Quality Index and European Quality of Life 5-Dimension 5-Level Utility Index scores significantly improved from baseline to weeks 12 and 48. At week 48, all 13 patients with a Dermatology Life Quality Index score of ≥2 and an absolute Psoriasis Area and Severity Index score of 0 to ≤2 reported itching. Limitations: Unclear generalizability of the results to other biologics. Conclusion: Treatment with brodalumab improved HRQoL in patients with psoriasis. Itching may contribute to incomplete HRQoL improvement in patients who have achieved clear or almost-clear skin.

Understanding and modifying Fabry disease: Rationale and design of a pivotal Phase 3 study and results from a patient-reported outcome validation study.

The use of available treatments for Fabry disease (FD) (including enzyme replacement therapy [ERT]) may be restricted by their limited symptom improvement and mode of administration. Lucerastat is currently being investigated in the MODIFY study as oral substrate reduction therapy for the treatment of FD. By reducing the net globotriaosylceramide (Gb3) load in tissues, lucerastat has disease-modifying potential to improve symptoms and delay disease progression. MODIFY is a multicenter, double-blind, randomized, placebo-controlled, parallel-group Phase 3 study (ClinicalTrial.gov: NCT03425539); here we present the rationale and design of this study. Eligible adults with a genetically confirmed diagnosis of FD and FD-specific neuropathic pain entered screening. Patients were randomized (2:1) to receive either oral lucerastat twice daily or placebo for 6 months; treatment allocation was stratified according to sex and ERT treatment status. The main objectives of MODIFY are to assess the effects of lucerastat on neuropathic pain, gastrointestinal (GI) symptoms, FD biomarkers, and determine its safety and tolerability. Neuropathic pain and GI symptoms are key features of FD that have a significant impact on quality of life. Despite various tools available to assess pain and GI symptoms, there are currently limited tools available to assess neuropathic and GI symptoms in FD, validated according to health authority guidelines. Based on FDA recommendations, we undertook a patient-reported outcome (PRO) validation study, using a novel eDiary-based PRO tool to assess the validity of evaluating neuropathic pain as a primary efficacy endpoint in MODIFY. Results from the PRO validation study are included. To date, MODIFY is the largest Phase 3 clinical study conducted in patients with FD. Enrollment to MODIFY is now complete, with 118 patients randomized. Results will be presented in a separate publication. Long-term effects of lucerastat are being assessed in the ongoing open-label extension study (NCT03737214).

Quantitative preoperative patient assessments are related to survival and procedure outcome for osseous metastases.

Aims: Our objective was to determine if preoperative patient-reported assessments are associated with survival after surgery for stabilization of skeletal metastases. Patients and Methods: All patients with metastatic cancer to bone and indications for skeletal stabilization surgery were approached to participate in a prospective cohort study at a tertiary care center from 2012 to 2017. Of the 208 patients who were eligible, 195 (94%) completed the 36-item Short Form Health Survey (SF-36) preoperatively and underwent surgical treatment of skeletal metastases with complete or impending fractures; the sample encompassed a range of cancer diagnoses and included cases of both internal fixation and endoprosthetic replacement. Cox proportional hazards models were used to identify associations between SF-36 scores and survival. Results: In a model adjusted for clinical factors, patients' mental and physical SF-36 component summary scores were significantly associated with survival, as was their SF-36 composite score (P = 0.004, P = 0.015, and P < 0.001, respectively). Scores in the general health, vitality, and mental health domains were each strongly associated with survival (P < 0.001). Conclusions: Patients' preoperative assessments of their health status are associated with their survival after surgery for skeletal metastases. Patient-reported assessments have the potential to contribute unique information to models that estimate patient survival, as part of efforts to provide optimal, individualized care and make informed decisions about the type and magnitude of surgery for metastatic bone disease that will last the patient's lifetime.

Expanding Personalized, Data-Driven Dermatology: Leveraging Digital Health Technology and Machine Learning to Improve Patient Outcomes.

The current revolution of digital health technology and machine learning offers enormous potential to improve patient care. Nevertheless, it is essential to recognize that dermatology requires an approach different from those of other specialties. For many dermatological conditions, there is a lack of standardized methodology for quantitatively tracking disease progression and treatment response (clinimetrics). Furthermore, dermatological diseases impact patients in complex ways, some of which can be measured only through patient reports (psychometrics). New tools using digital health technology (e.g., smartphone applications, wearable devices) can aid in capturing both clinimetric and psychometric variables over time. With these data, machine learning can inform efforts to improve health care by, for example, the identification of high-risk patient groups, optimization of treatment strategies, and prediction of disease outcomes. We use the term personalized, data-driven dermatology to refer to the use of comprehensive data to inform individual patient care and improve patient outcomes. In this paper, we provide a framework that includes data from multiple sources, leverages digital health technology, and uses machine learning. Although this framework is applicable broadly to dermatological conditions, we use the example of a serious inflammatory skin condition, chronic cutaneous graft-versus-host disease, to illustrate personalized, data-driven dermatology.

Real-world patient-reported outcomes of breast cancer or prostate cancer patients receiving antiresorptive therapy for bone metastases: Final results of the PROBone registry study.

Background: In breast cancer and prostate cancer patients, bone metastases (BM) present the main cause of morbidity and often cause debilitating pain, impaired functioning and subsequent deterioration of quality of life (QoL). The management of BM is still challenging. Maintenance or improvement in QoL is the main goal of treatment. Antiresorptive treatment, such as denosumab and bisphosphonates, can help to reduce the frequency of skeletal complications, to control bone pain and potentially to improve QoL. The optimal time point for initiation of antiresorptive therapy is still discussed controversially. In patients with BM, bone pain can be used as a surrogate measure of QoL. However, limited data exist on health-related QoL in patients with BM under antiresorptive treatment. The PROBone registry study evaluated complaints and limitations caused by BM of breast and prostate cancer patients using patient-reported outcomes (PROs) in real-world in Germany. Methods: Between 2014 and 2019, 500 patients with histological confirmation of advanced breast or prostate cancer, diagnosed with BM at start of their first antiresorptive therapy were prospectively enrolled in 65 outpatient-centers specialized in medical oncology across Germany. Changes of QoL were assessed monthly from baseline until a maximum of 12 months using the validated pain score Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) supplemented by questions on general pain and on the impact of time spent for treatment of illness on patients' daily activities. Statistical analysis was performed descriptively by relative and absolute frequencies. Results: In total, 486 patients were eligible for final analysis, of these 310 were diagnosed with breast cancer and 176 with prostate cancer. Median age was 67 years for breast cancer and 76 years for prostate cancer patients. 79.7% of breast cancer and 59.7% of prostate patients started antiresorptive treatment within 3 months after diagnosis of BM. More than 75% of patients suffered from bone pain at study inclusion. In total 52% of breast cancer patients and 47.9% of prostate cancer patients reported to take pain medication during the observation period. In breast and prostate cancer patients an initial pain reduction after start of BTA was observed: General pain and bone pain levels as well as the median FACT-BP score showed a constant improvement over the first months and maintained stable at a constant level afterwards. Subgroup analysis showed that patients without pain at baseline reported distinctly better FACT-BP scores throughout the whole observation period than patients with pain at baseline. Looking at time-stress (M)-scores, younger breast cancer patients (<65 years) showed highest burden especially during the first months of treatment. Conclusions: Our results indicate overall good adherence to current guideline recommendation, with most breast and prostate cancer patients starting antiresorptive therapy within the first 3 months after diagnosis of BM. This point gains even more importance as our data support current recommendations by ESMO guidelines as well as by German evidence-based S3-guidelines for diagnosis and treatment of breast and prostate cancer to initiate bone-targeted agents (BTA) as soon as BM are diagnosed, to keep pain levels at the lowest level possible, to minimize the debilitating effects of metastatic bone pain and maintain a good QoL. Bone pain management by an early use of BTA following BM diagnosis might improve patient care.

Feasibility, usability and acceptance of weekly electronic patient-reported outcomes among patients receiving pelvic CT- or online MR-guided radiotherapy - A prospective pilot study.

INTRODUCTION: The potential of patient symptoms being monitored longitudinally in radiotherapy (RT) is still unexploited. When novel technologies like online adaptive MR-guided radiotherapy (MRgRT) are evaluated, weekly electronic patient-reported outcomes (ePROs) may add knowledge about the symptom trajectory. This study aimed at evaluating feasibility, usability and acceptance of weekly ePRO among patients receiving pelvic radiotherapy. MATERIALS AND METHODS: In a mixed-methods convergent design, a prospective pilot study enrolled patients referred to pelvic radiotherapy with curative intent. Patients used their own device at home to self-report PRO weekly during and four weeks following radiotherapy and week 8, 12, and 24 (paper-questionnaire as an alternative). Feasibility was extracted from the ePRO software. The Patient Feedback Form and patient interviews were used to explore usability and patient acceptance. Patients were informed that clinicians had no access to PRO responses. RESULTS: In total, 40 patients were included; 32 patients with prostate cancer and 8 with cervical cancer (consent rate 87%), median age 68 (36-76). The majority did digital reporting (93%). 85% of patients responded to ≥80% of the weekly questionnaires with 91% average adherence to weekly completion (60% for follow-up), although lower for patients ≥age 70. Time spent on ePRO (97%) and frequency of reporting (92%) was considered appropriate. Interviews (n = 14) revealed the application was usable and the patients requested real-time feedback from the clinicians. CONCLUSION: Recruitment for ePRO during radiotherapy was feasible and adherence to weekly self-reporting high. The digital application was usable and weekly frequency and time spent acceptable. Real-time feedback from the clinicians is requested by the patients.

Understanding the Relationship Between Patient-Reported Function and Actual Function in the Upper Limb Prosthesis User Population: A Preliminary Study.

OBJECTIVE: To understand how perceived function relates to actual function at a specific stage in the rehabilitation process for the population using upper limb prostheses. DESIGN: Quantitative clinical descriptive study. SETTING: Clinical offices. PARTICIPANTS: A sample of 61 participants (N=61; mean age, 43.0±12.8y; 51 male/10 female) with upper limb amputation who use a prosthetic device and were in the definitive stage of a prosthesis fitting process. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A patient-reported outcome measure, the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH), and 2 performance-based outcome measures, Box and Blocks Test (BBT) and Capacity Assessment of Prosthesis Performance for the Upper Limb (CAPPFUL), were used as variables in multiple linear regression models. RESULTS: The multiple linear regression models, which controlled for prosthesis type and amputation level, did not show evidence that changes in the independent variable (DASH) are significantly associated with changes in the dependent variables (log(BBT) (B=-0.007; 95% confidence interval [CI], -0.015 to 0.001; P=.0937) and CAPPFUL (B=-0.083, 95% CI, -0.374 to 0.208; P=.5623)). In both models, individuals with elbow, transhumeral (above elbow), and shoulder disarticulation showed a significant negative association with the dependent variable (CAPPFUL or logBBT). In the CAPPFUL model, there was a significant negative association with individuals using a hybrid prosthesis (B=-20.252; 95% CI, -36.562 to -3.942; P=.0170). In the logBBT model, there was a significant positive association with individuals using body-powered prostheses (B=0.430; 95% CI, 0.089-0.771; P=.0157). CONCLUSIONS: Although additional data and analyses are needed to more completely assess the association between self-reported measures and performance-based measures of functional abilities, these preliminary results indicate that patient-reported outcomes alone may not provide a complete assessment of an upper limb prosthesis users' functional ability and should be accompanied by population-specific performance-based measures.

Complexity of design in early phase respiratory clinical trials; evaluating impact of primary endpoints and sponsor size.

Asthma and COPD represent most of the clinical trials in the respiratory area. The Primary Endpoint (PE) defines how trials are conducted. We hypothesised that small and mid-sized pharmaceutical companies may be innovative in the selection of their trial endpoints, to be time- and cost-effective. To test this, a record of industry-sponsored phase II trials in asthma, COPD and Asthma/COPD over 11 years was obtained. The type of PE and the influence these had on length, number of subjects and investigational trial sites were evaluated for the different disease categories. Differences in the type of PE used by large versus small/mid-sized companies were found for both asthma and COPD trials (p = 0.011 and 0.025), with sponsorship influencing the conduction of these. In asthma, studies sponsored by large companies were significantly longer than those from smaller companies (p = 0.0001). Additionally, large companies intended to recruit more subjects (asthma: p = 0.0048, COPD: p ≤ 0.0001) and use more investigational sites (asthma: p = 1 × 10-7, COPD: p = 1 × 10-5) than those from small and mid-size companies. A sub-analysis of the time and subject requirements associated with each type of PE did not provide an explanation for the differences observed. In conclusion, this exploratory analysis indicates differences in study size, duration and type of PE used by small/mid-sized and large companies. For some types of endpoints, differences in length and study size were found. However, it wasn't possible to attribute these differences between sponsors solely to the choice of PE, pointing out to the complexity of running clinical trials.

Exercise Training and Revascularization in the Management of Symptomatic Peripheral Artery Disease.

Exercise therapy and lower extremity revascularization both improve walking performance in symptomatic patients with peripheral artery disease. The combination of therapies provides greater benefit than either alone and may reduce the need for subsequent revascularization procedures, but further trials with longer follow-up are needed for the outcome of subsequent revascularization.

Chronic urticaria treatment patterns and changes in quality of life: AWARE study 2-year results.

BACKGROUND: A Worldwide Antihistamine-Refractory Chronic Urticaria (CU) patient Evaluation (AWARE) is a non-interventional, multicenter study including patients from Europe, Central and Latin America, Asia-Pacific, and the Middle East. AWARE describes real-world evidence for CU, including clinical characteristics, treatment patterns and the impact on quality of life. METHODS: Over the 2-year study, therapy changes, angioedema occurrence, and patient-reported outcomes (PROs) were recorded over 9 visits, including dermatology life quality index (DLQI) and 7-day urticaria activity score (UAS7). Data were stratified into subgroups: chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), or CSU + CIndU. RESULTS: Out of 4838 patients analyzed, 9.9% were receiving no treatment for their CU symptoms at baseline, and 20.4% were receiving first-line non-sedating H1-antihistamine at approved doses. The predominant baseline therapy was up-dosed non-sedating H1-antihistamines (25.5%). By Visit 2, omalizumab was the overall most commonly used therapy (29.6%), increasing to 30.1% by the end of the study. Baseline DLQI scores for patients with CSU, CIndU and CSU + CIndU were 8.3, 7.6 and 9.1, respectively; scores decreased over the study for CSU and CSU + CIndU patients, but fluctuated for CIndU patients. Baseline angioedema occurrence was higher in CSU and CSU + CIndU patients, reported in 45.4% and 45.5% of patients, respectively, compared to 17.0% in CIndU patients. By the final visit, angioedema had decreased to 11.9% and 11.2% for CSU and CSU + CIndU, respectively, and 9.6% for CIndU. CONCLUSION: CU patients are undertreated at baseline; after entering the AWARE study, more patients received appropriate treatment. However, over two thirds are not escalated to third-line treatments.

A prospective study of oral 5-aminolevulinic acid to prevent adverse events in patients with localized prostate cancer undergoing low-dose-rate brachytherapy: Protocol of the AMBER study.

BACKGROUND: Radiotherapy is one of the most frequently selected treatment options for patients with prostate cancer. However, adverse effects related to the irradiated surrounding normal organs are significant clinical concerns. Specifically, genitourinary and gastrointestinal toxicities can lead to a dramatically reduced quality of life. The aim of this clinical trial is to determine the efficacy of oral 5-aminolevulinic acid (ALA) phosphate with sodium ferrous citrate (SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. METHODS: The AMBER study is a prospective, single-center trial in patients with localized prostate cancer undergoing LDR-BT. Patients who undergo supplementary extra-beam radiotherapy are excluded, whereas those who undergo pre-implantation short-term (4-6 months) androgen deprivation therapy to decrease the prostate volume and/or improve oncological outcomes are included. After the screening and registration, the patients will be instructed to take capsules of ALA-SFC twice a day (200 mg and 229.42 mg per day) for 6 months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data will be collected before the implantation; during oral ALA-SFC treatment; and 1, 3, 6, 9, and 12 month(s) after seed implantation. The primary endpoint of this trial is the urinary frequency 3 months after seed implantation. At each visit, the 24-h urinary frequency, total voided volume, and mean voided volume on a frequency volume chart and other patient-reported outcomes are recorded. The data of the trial cases will be compared with those of historical controls, who are consecutive patients undergoing LDR-BT without supplementary extra-beam radiotherapy between January 2016 and January 2019. The number of subjects has been set to be 50 for trial cases and 150 for the historical control cases. Pre- and post-treatment clinicopathologic factors are compared between two groups. DISCUSSION: The goal of this trial is to determine the potential benefit of ALA-SFC in patients who undergo LDR-BT. To the best of our knowledge, this is the first study investigating the potential clinical benefit of oral ALA-SFC after radiotherapy. More evidence from a further randomized controlled trial is needed to change the standard of care and lead to better post-radiotherapy management. TRIAL REGISTRATION: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 5 December 2019. The reference number is jRCTs051190077, nara0013 (Certified Review Board of Nara Medical University).

Health-related quality of life and patient-reported outcome measures in NASH-related cirrhosis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is known to have a negative impact on patients' health-related quality of life (HRQoL), even before progression to cirrhosis has occurred. The burden of NASH-related cirrhosis from the patient perspective remains poorly understood. Herein, we aimed to identify the burden of disease and HRQoL impairment among patients with NASH-related compensated cirrhosis. METHODS: This targeted literature review sought first to identify the humanistic burden of disease from the perspective of patients with diagnosed NASH-cirrhosis and, secondly, to identify generic or disease-specific patient-reported outcome measures (PROMs) used to assess the impact of NASH-cirrhosis. Searches were conducted in bibliographical databases, grey or unpublished literature, liver disease websites, support group websites and online blogs. A quality assessment of specific PROMs was conducted. RESULTS: Patients with NASH-cirrhosis are reported to suffer from lower HRQoL than patients with non-cirrhotic NASH and the general population with respect to physical health/functioning, emotional health and worry, and mental health. Thirteen PROMs were identified, of which 4 were liver-disease specific: CLDQ, CLDQ-NAFLD, LDQoL and LDSI. The most commonly used measures do not comply with current industry or regulatory standards for PROMs and/or are not validated for use in a cirrhotic NASH population. CONCLUSIONS: Patients with NASH-cirrhosis have lower HRQoL and poorer physical health than patients with non-cirrhotic NASH. However, the literature lacked detail of the everyday impact on patients' lives. Currently, a number of PROMs are available to measure the impact of the disease in patients with chronic liver conditions. The lack of studies that include qualitative insights in this population mandates further exploration and research. LAY SUMMARY: It is not well understood how having non-alcoholic fatty liver disease (NAFLD)-related cirrhosis affects a person's everyday wellbeing and quality of life. Some research has been done with patients who have early stages of liver disease but not people with cirrhosis. We found that patients with NAFLD-related cirrhosis tended to have poorer health than patients without cirrhosis. But there was not very much information from patients themselves and there were no tools or questionnaires just for this group of patients.

Identifying organs at risk for radiation-induced late dysphagia in head and neck cancer patients.

BACKGROUND AND PURPOSE: Dysphagia is a common, severe and dose-limiting toxicity after oncological treatment of head and neck cancer (HNC). This study aims to investigate relationships between radiation doses to structures involved in normal swallowing and patient-reported as well as clinically measured swallowing function in HNC patients after curative (chemo-) radiation therapy (RT) with focus on late effects. MATERIALS AND METHODS: Patients (n = 90) with HNC curatively treated with RT ±â€¯chemotherapy in 2007-2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific symptom score was used to determine patient-reported dysphagia. The Penetration-Aspiration Scale (PAS) was applied to determine swallowing function by VFS (PAS ≥ 4/ ≥ 6 = moderate/severe dysphagia). Thirteen anatomical structures involved in normal swallowing were individually delineated on the patients' original planning CT scans and associated dose-volume histograms (DVHs) retrieved. Relationships between structure doses and late toxicity were investigated through univariable and multivariable logistic regression analysis (UVA/MVA) accounting for effects by relevant clinical factors. RESULTS: Median assessment time was 7 months post-RT (range: 5-34 months). Mean dose to the contralateral parotid gland and supraglottic larynx as well as maximum dose to the contralateral anterior digastric muscle predicted patient-reported dysphagia (AUC = 0.64-0.67). Mean dose to the pharyngeal constrictor muscle, the larynx, the supraglottic larynx and the epiglottis, as well as maximum dose to the contralateral submandibular gland predicted moderate and severe dysphagia by VFS (AUC = 0.71-0.80). CONCLUSION: The patients in this cohort were consecutively identified pre-treatment, and were structurally approached and assessed for dysphagia after treatment at a specific time point. In addition to established dysphagia organs-at-risk (OARs), our data suggest that epiglottic and submandibular gland doses are important for swallowing function post-RT. Keeping DVH thresholds below V60 = 60% and V60 = 17%, respectively, may increase chances to reduce occurrence of severe late dysphagia. The results need to be externally validated in future studies.

Patient-reported outcomes after breast reconstructive surgery: A prospective cross-sectional study.

BACKGROUND: With advancements in and the evolution of the medical field, several methods and surgical techniques have been developed for breast reconstruction after mastectomy. Generally, we can categorize these strategies into two broad groups: autologous reconstruction and implant-based reconstruction. This study aimed to analyze the satisfaction rate between these groups, considering age, timing of breast reconstruction, body mass index (BMI), major complications, and the need for radiotherapy or chemotherapy. MATERIALS AND METHODS: All the patients who underwent a mastectomy and subsequent breast reconstruction surgery at our institution between August 1, 2013, and August 31, 2017, were invited to complete a BREAST-Q questionnaire. To compare the quality of life and complication rate between the autologous and implant-based reconstruction groups, data were collected from specific patients. All participants completed the Arabic version of the postoperative reconstruction module. RESULTS: Among 61 patients, 43 (70.5%) completed the two domains of the BREAST-Q questionnaire, about the satisfaction with the implanted breast and satisfaction with the surgical outcome. These patients were divided into two groups: autologous (n = 21) and implant-based (n = 22) groups. The mean score of satisfaction with the implanted breast was 43.5 for the autologous group and 39.6 for the implant-based group. For the surgical outcome, the scores for the autologous and implant-based groups were 45.4 and 56.0, respectively. However, there was neither a statistical significance in the satisfaction with the implanted breast nor the surgical outcome between the two groups. CONCLUSION: Although there are many different surgical techniques to reconstruct a breast after mastectomy, there is still no specific surgical method that is perfect or well-suited for all patients undergoing breast reconstruction surgery. In our study, we found that there was no significant difference in satisfaction between the ABR and IBR group.

A real-world study assessing the use of bone-targeted agents and their impact on bone metastases in patients with prostate cancer treated in clinical practice in Europe.

BACKGROUND: Bone metastases (BMs) are common in patients with prostate cancer and can lead to skeletal-related events (SREs), which are associated with increased pain and reduced quality of life (QoL). Bone-targeted agents (BTAs), such as zoledronic acid and denosumab, reduce the incidence of SREs and delay progression of bone pain. METHODS: We evaluated the management of BMs and pain in six European countries (Belgium, France, Germany, Italy, Spain and the UK) using the Adelphi Prostate Cancer Disease Specific Programme. Patient-reported outcomes (PROs) were used to assess the impact of BMs on pain and QoL. RESULTS: In total, 358 physicians completed Patient Record Forms, of whom 246 were oncologists and 112 were urologists. Data were collected on 3667 patients with prostate cancer, including 1971 with BMs and 551 with metastases at sites other than bone (non-BMs). PROs were assessed in 573 patients with BMs and 220 with non-BMs. Most patients with BMs (74%) received a BTA and 53% received treatment within 3 months of BM diagnosis. Patients treated by oncologists were more likely than those treated by urologists to receive a BTA (78% vs. 60%) and to have treatment initiated within 3 months of BM diagnosis (56% vs. 43%). For patients who did not receive a BTA, the main reasons for not treating were very recent BM diagnosis and a perceived low risk of bone complications. Data collected by physicians showed that most patients with BMs (97%) were taking analgesics, with 30% receiving strong opioids. Despite this, 70% were currently experiencing bone pain and 28% were experiencing moderate to severe pain. PRO pain measures showed that 70% of patients with BMs were experiencing moderate to extreme pain, suggesting a disparity between pain levels reported by physicians and by patients. CONCLUSIONS: Although most patients with BMs receive a BTA, there remain a proportion of patients who are not receiving adequate treatment to prevent SREs or manage pain. Oncologists are more likely to adhere to clinical guidelines than urologists for the prescription of BTAs. Bone pain is common and undertreated. Increasing awareness of SRE prevention and bone pain management might improve patient care.

Bone-targeted agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in real-world practice in six European countries.

BACKGROUND: Bone metastases (BMs) are common in patients with breast cancer and can lead to skeletal-related events (SREs), which are associated with increased pain and reduced quality of life (QoL). Bone-targeted agents (BTAs), like zoledronic acid and denosumab, reduce the incidence of SREs and delay progression of bone pain. MATERIALS AND METHODS: We evaluated the management of BMs and pain in six European countries (Belgium, France, Germany, Italy, Spain, and UK) using the Adelphi Breast Cancer Disease Specific Programme, which included a physician survey and patient-reported outcomes (PROs) to assess the impact of BMs on pain and QoL. RESULTS: 301 physicians completed patient record forms for 2984 patients with advanced breast cancer; 1408 with BMs and 1136 with metastases at sites other than bone (non-BMs). Most patients with BMs (88%) received a BTA, with 81% receiving treatment during 3 months following BM diagnosis. For those who did not receive a BTA, the main reasons given were: very recent BM diagnosis, perceived low risk of bone complications, and short life expectancy. Most patients with BMs (68%) were experiencing bone pain and, of these, 97% were taking analgesics (including 28% receiving strong opioids). Despite this, moderate to severe pain was reported in 20% of patients who were experiencing pain. PROs were assessed in 766 patients with advanced breast cancer (392 with BMs, 374 with non-BMs). Overall, patients with BMs reported worse pain and QoL outcomes than those with non-BMs, those not receiving a BTA reported worse pain. CONCLUSION: Despite the large proportion of patients receiving BTAs in this study, some patients with BMs are still not receiving early treatment to prevent SREs or to manage pain. Improving physicians' understanding of the role of BTAs and the importance of early treatment following BM diagnosis has the potential to improve patient care.

Inadequacy of 3-month Oswestry Disability Index outcome for assessing individual longer-term patient experience after lumbar spine surgery.

OBJECTIVE Prospective longitudinal outcomes registries are at the center of evidence-driven health care reform. Obtaining real-world outcomes data at 12 months can be costly and challenging. In the present study, the authors analyzed whether 3-month outcome measurements sufficiently represent 12-month outcomes for patients with degenerative lumbar disease undergoing surgery. METHODS Data from 3073 patients undergoing elective spine surgery for degenerative lumbar disease were entered into a prospective multicenter registry (N(2)QOD). Baseline, 3-month, and 12-month follow-up Oswestry Disability Index (ODI) scores were recorded. The absolute differences between actual 12- and 3-month ODI scores was evaluated. Additionally, the authors analyzed the absolute difference between actual 12-month ODI scores and a model-predicted 12-month ODI score (the model used patients' baseline characteristics and actual 3-month scores). The minimal clinically important difference (MCID) for ODI of 12.8 points and the substantial clinical benefit (SCB) for ODI of 18.8 points were used based on the previously published values. The concordance rate of achieving MCID and SCB for ODI at 3-and 12-months was computed. RESULTS The 3-month ODI scores differed from 12-month scores by an absolute difference of 11.9 ± 10.8, and predictive modeling estimations of 12-month ODI scores differed from actual 12-month scores by a mean (± SD) of 10.7 ± 9.0 points (p = 0.001). Sixty-four percent of patients (n = 1982) achieved an MCID for ODI at 3 months in comparison with 67% of patients (n = 2088) by 12 months; 51% (n = 1731) and 61% (n = 1860) of patients achieved SCB for ODI at 3 months and 12 months, respectively. Almost 20% of patients had ODI scores that varied at least 20 points (the point span of an ODI functional category) between actual 3- and 12-month values. In the aggregate analysis of achieving MCID, 77% of patients were concordant and 23% were discordant in achieving or not achieving MCID at 3 and 12 months. The discordance rates of achieving or not achieving MCID for ODI were in the range of 19% to 27% for all diagnoses and treatments (decompression with and without fusion). The positive and negative predictive value of 3-months ODI to predict 12-month ODI was 86% and 60% for MCID and 82% and 67% for SCB. CONCLUSIONS Based on their findings, the authors conclude the following: 1) Predictive methods for functional outcome based on early patient experience (i.e., baseline and/or 3-month data) should be used to help evaluate the effectiveness of procedures in patient populations, rather than serving as a proxy for long-term individual patient experience. 2) Prospective longitudinal registries need to span at least 12 months to determine the effectiveness of spine care at the individual patient and practitioner level.