The Common Terminology Criteria for Adverse Events (CTCAE) is the established toxicity scoring system that assigns severity grades (G1 = mild to G5 = death) to Adverse Events (AEs). Compared to CTCAE v3.0 (2006), updated versions introduced changes in severity grade definitions. This study evaluated changes between v3.0 and v5.0 (2017) for AEs in gynaecological radiotherapy.

After selecting AEs relevant for gynaecological radiotherapy in v3.0, changes in severity grades were identified using CTCAE v3.0-to-v5.0 mapping tables. Six radiation oncologists (ROs) evaluated severity grade definitions for changes in: clinical interpretation, subjective (patient-reported symptoms) and objective (details on medication/intervention) information, and expected severe (≥G3) events. Agreement was based on at least five (≥5)ROs.

Gastrointestinal, urinary, reproductive, general and injury/musculoskeletal AEs were selected (n = 118). G4 definitions in v5.0 were removed in 22 % of AEs. ≥5ROs agreed on changes affecting clinical interpretation especially for G2 (31 %) and G3 (30 %). For subjective information, 18 % of G2 and 15 % of G3 were judged relying more on patient-reported symptoms. Less objective information was found in 51 % of G3 definitions. Variability in agreement was observed especially for subjective information in G3 and expected ≥G3 events.

This analysis revealed that severity grade definitions in v3.0 and v5.0 for AEs in gynaecological radiotherapy present changes with potential impact on scoring in clinical studies. Notably, 22 % of AEs in v5.0 no longer have G4 defined, and G3 definitions often include fewer details on medication/intervention. Variability in ROs' interpretations is frequently observed, highlighting the need for education to standardise toxicity scoring.

In pediatric palliative care (PPC), patients often are not able to report symptoms so proxy reports from parents are used. Whether psychological distress in the proxies affects reports of patients' symptoms is unknown.

To measure the influence of parents' distress on proxy-reported scores regarding symptoms by analyzing pairs of parents reporting on the same child.

In a large prospective cohort study of PPC patients, we collected parents' reports of child symptoms (Memorial Symptom Assessment Scale) and their own psychological distress (Kessler-6). In this quasi-experimental design study, we examined data from pairs of parents reporting symptoms for the same child. Using regression modelling, we estimated the association between parental distress scores and patient total symptom scores across the entire sample accounting for clustering within families, and then measured the association within-families of the absolute differences of the two parents' distress and the difference in their symptom scores.

Among 152 parents in 76 families, 50.0% were female, 80.9% were White, and the mean age was 36.4 (SD 9.0) years. Across the sample, each 1-point increase in reported parental distress was associated with a 1.07 (95% CI, 0.87-1.28; P < 0.001) increase in proxy-reported patient symptom score. Within families, relative to the other parent, each 1-point increase in the difference of the distress scores was associated with a 0.33-point (95% CI, 0.32-0.35; P = 0.006) increase in the difference in symptom scores.

Psychological distress appears to influence proxy reports of symptoms which has implications for future research and clinical practice.

This work evaluated and validated the translation and cross-cultural adaptation of 4-Domain Sport PROM (4-DSP) into Chinese, assessing its understandability and reproducibility in all questionnaire domains for Chinese-speaking patients.

Cross-sectional study, level of evidence II. Twenty patients with sports injuries who underwent surgical treatment and postoperative rehabilitation in the Sports Medicine Surgery Department of Huashan Hospital were selected to evaluate whether the translation was understandable. Then, the 4-DSP was applied to 120 patients who had undergone trauma surgical procedures. The translation and cross-cultural adaptation of 4-DSP involved 6 steps: (1) Translation, (2) Synthesis of translation, (3) Back Translation, (4) Testing of the Prefinal Version-Expert committee review, (5) Prefinal testing among the patients, and Reliability and Consistency Testing. The questionnaire was self-administered by 120 patients (53 males and 67 females; mean age: 30.41 ± 6.8 years.) who had undergone arthroscopic surgery or conservative therapy from a sports physical therapist and had 3-month to 1-year follow-up. All patients filled in the 4-DSP questionnaire without direct supervision of their trainer/coach or researcher. All data were collected and processed anonymously.

97% of the experts (n = 10) considered the translation accuracy understandable; each item and overall content validity showed 96% agreement, and the bilingual translation accuracy was rated as 98.5%, presenting a global Cronbach's alpha of 0.72.

The Chinese cross-cultural adaptation and validation of the original English version of the 4-DSP questionnaire proved reproducible and properly understandable in all four domains. It can safely and reliably assess treatment outcomes for sports injuries in Chinese-speaking patients and is a helpful tool to collect and assess athletic population data.

Understanding and integrating patients' preferences into clinical practice can enhance personalized care, improve patient's adherence to treatment, and lead to better therapeutic outcomes. The aim of this scoping review was to map the existing literature investigating patients' preferences in periodontal and implant therapy while identifying key areas for future research and development.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines, an electronic search was conducted in four databases (PubMed, Google Scholar, Cochrane Library, and ScienceDirect) in July 2024 to identify studies evaluating patients' preferences for periodontal and implant therapy.

The literature search yielded 384 studies, of which eight articles met the inclusion criteria. These studies were conducted between 2003 and 2019 in Brazil, China, Austria, Italy, Germany, Canada, USA, Chile, France, Spain, and Portugal. A total of 1642 patients were included. Preferences were assessed using various quantitative and mixed methodologies. Results indicate a strong preference for treatments aimed at preserving teeth, favoring conservative approaches. When teeth cannot be restored, most patients prefer an implant-supported fixed partial denture to avoid damaging adjacent teeth with a conventional tooth-supported fixed partial denture. In this context, treatment predictability is ranked as the most important factor. While no sociodemographic factors appeared to be associated with preferences in periodontal treatments, several predictors were identified for dental implant therapy. Younger patients, women, individuals with higher education levels, and those with high perceived dental health showed a higher willingness to pay for dental implants.

The literature on patients' preferences in periodontal and implant therapies is scarce. Several trends are identified but further longitudinal studies are needed to explore patients' preferences over time and the role of sociodemographic and cultural segmentation criteria.

Exercising at a specific time of day has the potential to mitigate the negative effects of disrupted circadian rhythms caused by irregular work and sleep schedules on the development of chronic diseases. Afternoon/evening exercise is postulated to be superior to morning exercise for various health outcomes, but patient acceptance of timed exercise remains unclear. The aim of this systematic review was to assess the impact of exercise timing on patient-reported outcomes (PROMs).

We conducted a systematic review, following Cochrane and PRISMA guidelines (PROSPERO: CRD42022322646). We systematically searched databases including MEDLINE, SCOPUS, Embase, APA PsycInfo, CINAHL, and Web of Science, to identify studies which reported on PROMs related to timed exercise interventions: either acutely after a bout of exercise or following extended training (>1 month). Studies were included if they reported primary data from randomized or non-randomized experiments of timed exercise interventions (against any comparator), published in English until August 2023 and reporting on any PROM. Machine-learning software (AR Reviews) was used to aid in abstract screening. Subsequently, two independent reviewers reviewed the included full texts, extracted study details (participants, interventions, outcomes), and evaluated the risk of bias using Cochrane tools (ROB-2 and ROBINS-I). Exercise interventions were summarized using the TIDieR reporting method and results were presented in accordance with the Synthesis Without Meta-analysis (SWiM) guidelines for systematic reviews.

Seventeen studies with 403 participants were included in the review. The interventions varied widely in exercise modality, duration, and participant characteristics, contributing to substantial heterogeneity in the findings. Most studies found no significant impact of exercise timing on PROMs. There was some inconsistency between studies for certain outcomes.

The review suggests that there are no clear detrimental effects of afternoon or evening exercise on PROMs compared to morning exercise. However, the lack of homogeneity in study populations and small sample sizes resulting in low power for PROM outcomes are major limitations of the research in this field. If future research confirms the metabolic advantages of afternoon/evening exercise, this may be an acceptable alternative for individuals.

In SURMOUNT-2, a phase 3, randomized clinical trial, tirzepatide treatment resulted in clinically meaningful reduction in bodyweight among people with obesity or overweight and T2D. The current analysis evaluated the effects of tirzepatide treatment on self-reported health-related quality of life (HRQoL) outcomes among SURMOUNT-2 participants.

SURMOUNT-2 participants were randomly assigned (1:1:1) to receive either tirzepatide 10 mg (n = 312), tirzepatide 15 mg (n = 311), or placebo (n = 315) for 72 weeks as an adjunct to diet and exercise. Self-reported HRQoL was assessed in terms of changes from baseline to week 72 in Short Form-36 Version 2 Health Survey acute form (SF-36v2), Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), EQ-5D 5-level Version (EQ-5D-5L) Health State Index (UK) and associated EQ visual analog scale (VAS), and Patient Global Impression of Status (PGIS) for Physical Activity. Post hoc analyses evaluated changes in HRQoL outcomes by categorical percent weight reduction targets (> 0 to < 5%, ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%) and by self-reported baseline physical function limitations (based on PGIS) among tirzepatide-treated participants.

At week 72, tirzepatide treatment was associated with significantly larger improvements than placebo in the SF-36v2 Physical Component Summary score, SF-36v2 physical functioning, bodily pain, general health, vitality, and social functioning domain scores, all IWQOL-Lite-CT scores, and EQ VAS score. Tirzepatide-treated participants who achieved greater weight reduction targets showed numerically larger improvements in HRQoL scores relative to those with lower percent weight reduction. For all HRQoL measures, participants with physical function limitations at baseline showed greater improvements than those without limitations.

Tirzepatide treatment was associated with improved self-reported HRQoL outcomes compared with placebo among people with obesity or overweight with T2D. Participants achieving greater bodyweight reductions and those with physical function limitations at baseline showed greater improvements in HRQoL. CLINICAL TRIAL REGISTRATION NUMBER FOR SURMOUNT-2: NCT04657003.

Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients.

To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6.

We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls. Participants were seen every 6 months for 2 years. Mixed models were used to estimate change over 12- and 24-months of follow-up. Changes on the FARS-FS and PGI-C were used as anchors to estimate meaningful changes.

Among persons with SCA, mean age was 48.7 years and mean SARA score was 9.3. Few measures showed statistically significant changes at 12 months. At 24-months, the FARS-ADL, PROM-Ataxia total, PROM-Ataxia physical, and PROM-Ataxia ADL scores showed the strongest associations of change.

Patient reported or derived outcome measures, such as FARS-ADL and ADL sub domain of the PROM-Ataxia, can capture longitudinal change in patients' symptom experience over a 2-year period and its impact on daily activities, even in those with early disease. More work is needed to identify outcomes that reliably capture change earlier.

Poly (ADP-ribose) polymerases (PARPs) are enzymes essential for detecting and repairing DNA damage through poly-ADP-ribosylation. In cancer, cells with deficiencies in homologous recombination repair mechanisms often become more dependent on PARP-mediated repair mechanisms to effectively repair dsDNA breaks. As such, PARP inhibitors (PARPis) were introduced into clinical practice, serving as a key targeted therapy option through synthetic lethality in the treatment of cancers with homologous recombination repair deficiency (HRD). Though PARPis are currently approved in the adjuvant setting for several cancer types such as ovarian, breast, prostate and pancreatic cancer, their potential role in the neoadjuvant setting remains under investigation. This review outlines the rationale for using PARPi in the neoadjuvant setting and evaluates findings from early and ongoing clinical trials.

Our analysis indicates that numerous studies have explored PARPi as a neoadjuvant treatment for HRD-related cancers. The majority of neoadjuvant PARPi trials have been performed in breast and ovarian cancer, while phase II/III evidence supporting efficacy in prostate and pancreatic cancers remains limited. Studies are investigating PARPi in the neoadjuvant setting of HRD-related cancers. Future research should prioritize combination strategies with immune checkpoint inhibitors and expand outcome measures to include patient satisfaction and quality-of-life metrics.

Despite recent improvements in treatment modalities for cystic fibrosis (CF), there is currently limited evidence and a lack of consensus regarding optimal treatment strategies for the different aspects of CF, including pulmonary exacerbations (PEx). We aimed to establish a prospective cohort of people with CF (pwCF) to evaluate alternative approaches to managing CF in the era of modulator therapies.

We prospectively enrolled children and adults with CF receiving care at specialist CF centres across Australia. Participant data were systematically collected on demography, clinical signs and symptoms, comorbidities, spirometry, participant reported outcomes, microbiology and treatments received. Here we describe the demographic, microbiological and clinical characteristics of the participants at enrolment, to understand the representativeness of the cohort for planning future nested studies.

Between October 14, 2020 and December 31, 2023, 927 pwCF were enrolled across eleven Australian CF centres. Of these, 51% (n=472) were male, 77% (n=709) were <18 years old, 90% (n=831) had a highest ppFEV1 (percent predicted forced expiratory volume exhaled in the first second) of ≥70% in the preceding year, and 35% (n=322) reported detection of Pseudomonas aeruginosa in their airway specimens.

We have established a contemporary cohort of pwCF with granular clinical and treatment data for PEx. This cohort will enable future nested studies focused on PEx management and other aspects of CF care. Understanding the baseline characteristics of these participants, as presented here, is critical for interpreting subsequent outcomes and for identifying factors that may influence disease progression and response to therapies.

Power training has gained attention as a method for enhancing functional performance and mitigating fall risk in older adults, yet its long-term feasibility and safety, particularly in ballistic resistance training, remain underexplored in postmenopausal women. We evaluated the feasibility of 8-month ballistic resistance training compared with conventional resistance training in postmenopausal women.

The Resistance Exercise Programme on Risk of Osteoporosis and Osteoarthritis in Females (REPROOF) study was a three-arm parallel group randomised controlled trial at a university lab in the UK. Healthy postmenopausal women (n = 109) were randomised to 30 weeks (2 sessions/week) of lower-body ballistic resistance training, conventional resistance training, or a non-exercising control group.

The primary outcomes, collected by questionnaire, were process feasibility, acceptability, perceived exercise efficacy, and adverse events.

Eighty-two participants completed the trial (75.2 % retention). Both ballistic resistance training and conventional resistance training were well accepted, with most participants rating the intervention positively. No differences in the perceived improvements in physical function and psychological well-being were found between the resistance training groups. Similarly, there was no significant difference in the rate of muscle-related adverse events between the resistance training groups (ballistic, 2.7 per 100 person-weeks; conventional, 2.3 cases per 100 person-weeks), but the rate was significantly lower in the control group (0.9 cases per 100 person-weeks). No serious adverse events occurred during or within 24 h of exercise sessions.

The absence of serious adverse events and the observed positive outcomes confirm the safety, satisfaction, and perceived effectiveness of ballistic resistance training, suggesting its potential for broader application in healthy postmenopausal women.

gov registry ID NCT05889598.

The aim of this scoping review was to identify validated instruments measuring Patient-Reported Outcome Measures (PROMs) used in research and clinical practice that are deigned to measure the health-related quality of life (HRQoL) of people with chronic wounds.

Scoping literature review.

A search of the electronic databases MEDLINE, PubMed, CINAHL, Web of Science, and Scopus that spanned the years 1990 to April 2024 was conducted. The initial search resulted in 13 094 records. Removal of duplicates, title and abstract searches, and final selection of elements that were read in full yielded 30 records, along with 2 records identified from reference lists of critical articles.

Twelve validated instruments measuring PROMs assessing HRQoL were identified; 6 were generic and 6 were specific to chronic wounds. The most frequently used generic instruments were the Short Form 36 Health Survey Questionnaire and the EuroQol-five Dimensions-Five levels; they were used in 6 (18.8%) and 3 (9.4%) studies, respectively. The Cardiff Wound Impact Schedule and the Wound-Qol were the most frequently wound-specific instruments; both were applied in 5 (15.6%) studies each. Both condition-specific and generic instruments measure 1 or more conceptual domains that cover the multidimensionality of HRQoL. Generic instruments allow comparison of persons with chronic wounds to populations with other chronic conditions and the general population; however, generic instruments may underestimate changes in QoL in populations with chronic wounds. Condition-specific instruments provide additional information about HRQoL and they are more likely to be responsive to the effects of specific interventions.

Research related to instruments that measure PROMs for HRQoL for patients with chronic wounds is limited. Additional research such as longitudinal and randomized studies are needed to strengthen the evidence regarding the applicability and dissemination of PROMS to assess HRQoL in this population.

The objective of this systematic review and meta-analysis (SRMA) was to evaluate the impact of electronic patient-reported outcomes (ePROs) on health-related quality of life (HRQoL) in patients with cancer.

We performed SRMA of randomised controlled trials (RCTs) comparing ePRO interventions with usual care in patients with cancer. The primary outcome was HRQoL. We used a random effects model a priori due to the anticipated clinical heterogeneity. Subgroup analyses and meta-regressions were performed to explore sources of heterogeneity. After assessing the risk of bias using risk-of-bias tool (RoB V.2), we rated the evidence certainty using the Grading of Recommendations, Assessment, Development and Evaluations framework.

We included studies meeting the following criteria: (1) RCTs; (2) patients diagnosed with any type of cancer, undergoing or having completed treatment; (3) comparing ePROs with usual care without ePRO interventions; (4) assessing the effect on HRQoL.

We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to April 2024.

We screened 7706 records to include 36 RCTs with 9608 patients. ePRO interventions showed a standardised mean difference (SMD) of 0.35; 95% CI 0.18 to 0.51 compared with usual care. Patients receiving ongoing therapy had an SMD of 0.39 (95% CI 0.21 to 0.58), while those who had completed therapy had an SMD of 0.12 (95% CI 0.01 to 0.22), with a significant subgroup difference (p=0.01). No statistically significant differences were observed across the method of ePRO assessment, cancer site, metastasis status, therapy status, average age or duration of ePRO use. The results remained consistent with Bayesian and other sensitivity analyses.

ePRO interventions improve HRQoL more than usual care in patients with cancer, with greater effect in those currently undergoing therapy. This improvement is independent of cancer type, duration of ePRO use or patient age. Future research should address sources of heterogeneity, explore long-term impacts and develop strategies to increase patient engagement and adherence to ePRO systems.

CRD42024531708.

Heart failure (HF) is one of today's leading public health issues worldwide. The sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin recently received a label expansion. It is now approved for treatment of HF across the entire spectrum of ejection fraction (EF) in Germany. However, real-world data are limited. EVOLUTION-HF DEallEF aims to complement existing data in Germany under the multinational umbrella EVOLUTION-HF study protocol.

EVOLUTION-HF DEallEF (NCT06336330) is a non-interventional, prospective, longitudinal cohort study. It is planned to enrol a total of 1000 (700 evaluable) patients with HF in Germany. Distribution is planned as 40% patients with preserved (HFpEF), 20% with mildly reduced (HFmrEF), and 40% with reduced EF (HFrEF). Patients ≥18 years of age, who started dapagliflozin treatment 14-90 days prior to enrolment according to the local product label, are eligible to participate. Among reasons for exclusion are previous SGLT2i treatment (including dapagliflozin), type 1 diabetes, and hypersensitivity to dapagliflozin or its excipients. Data on medical history, HF status and medication before dapagliflozin treatment will be collected retrospectively at baseline. Follow-up data will concern clinical symptoms, healthcare utilization, HF and concomitant medication, as well as dapagliflozin usage. These data will be extracted from real-world data sources like patient charts, discharge letters, and electronic medical records. They will be collected prospectively every 3 months for up to 12 months. In addition, patient-reported outcomes (PROs) on health-related quality of life (HRQoL), medication adherence, work productivity, and patient's needs, expectations, and satisfaction with medical care will be collected using standardized and unstandardized questionnaires. Primary objectives include demographic and clinical characterization of patients and the assessment of treatment patterns of dapagliflozin, other HF medications, and glucose-lowering medications. Secondary objectives are to describe HRQoL, medication adherence, and work productivity. Exploratory objectives are to describe depression, healthcare utilization, and patient's needs, expectations, and satisfaction with medical care. EVOLUTION-HF DEallEF has included its first patient in April 2024 and is currently open for enrolment.

EVOLUTION-HF DEallEF will deliver relevant insights into real-world dapagliflozin treatment for HF focusing on clinical and patient perspective in Germany.

GP2015 is an etanercept biosimilar. Equivalent efficacy and comparable safety of GP2015 to reference etanercept (ref-ETN) was demonstrated in two phase III studies, one in patients with moderate-to-severe chronic plaque-type psoriasis (PsO; EGALITY study) and the other in patients with rheumatoid arthritis (RA; EQUIRA study). EGALITY also included patients with reported psoriatic arthritis (PsA). Here, patient-reported outcome (PRO) data from both studies are presented.

EGALITY included 531 patients with PsO and EQUIRA included 376 patients with RA. In EGALITY, patients who had achieved ≥ 50% improvement in Psoriasis Area and Severity Index (PASI) at week 12 either continued the initial treatment or underwent three treatment switches between GP2015 and ref-ETN starting at week 12. In EQUIRA, patients with at least moderate European League Against Rheumatism response at week 24 received GP2015 up to week 48. Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in EGALITY, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score in EQUIRA, and Health Assessment Questionnaire-Disability Index (HAQ-DI) in both studies.

In EGALITY, mean DLQI decreased from baseline in the GP2015 and ref-ETN groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at week 12 (GP2015, - 67.7 [40.7]; ref-ETN, - 67.3 [30.6]), and were sustained after the switch at week 52 ('continued GP2015,' - 77.3 [36.5]; 'continued ref-ETN,' - 72.8 [33.7]; 'switched GP2015,' - 73.9 [37.0]; 'switched ref-ETN,' - 78.1 [30.9]). The proportion of patients with EQ-5D-5L scores of 1 ('no problems') improved from baseline to week 52 for all five dimensions and was comparable between treatment groups. In EGALITY, in patients with reported PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline, and scores were comparable between treatment groups at week 12 (GP2015, 0.6 [0.7]; ref-ETN, 0.6 [0.6]) and after switching at week 52 ('continued GP2015,' - 0.4 [0.6]; 'continued ref-ETN,' - 0.4 [0.6]; 'switched GP2015,' - 0.4 [0.6]; 'switched ref-ETN,' - 0.1 [0.4]). In EQUIRA, the proportion of patients achieving HAQ-DI in normal range (≤ 0.5) was comparable between treatment groups up to week 48 ('continued GP2015,' 36.7%; 'switched to GP2015,' 39.9%). The mean FACIT-Fatigue scores increased from baseline and the mean (SD) percent change from baseline in FACIT-Fatigue score at week 24 was 9.6 (9.5) in the 'continued GP2015' and 11.4 (9.7) in the 'switched to GP2015' groups; the scores were sustained after switching until week 48.

Treatment with GP2015 and ref-ETN resulted in similar improvements in PROs and quality-of-life scores across the three diseases, namely RA, PsA, and PsO. These improvements were sustained after switching, with consistent benefit on PROs during the treatment period.

ClinicalTrials.gov identifiers: NCT01891864, NCT02638259.

Patient-reported outcome measures (PROMs), the gold standard for outcome assessment in spine surgery, exhibit variability over time. Incomplete PROM collection, however, introduces nonresponse bias and limits the generalizability of time-based analyses of outcomes.

This study compared PROM-respondents and nonrespondents in spine surgery to characterize survey nonresponse and improve equitable patient representation in time series PROM analyses.

Retrospective study.

Patients undergoing surgery at a large, tertiary care center in the United States between July 2009 and February 2023 for lumbar spinal stenosis without spondylolisthesis (LSS), lumbar spinal stenosis with spondylolisthesis (LSP), or cervical spondylotic myelopathy (CSM).

The primary outcome was completeness of available PROM records, which was defined as having Patient-Reported Outcomes Measurement Information System (PROMIS)-Global Health scores once within 2 years preoperatively and twice within 2 years postoperatively.

Demographic variables of age, sex, race, marital status, employment, insurance, body mass index (BMI), smoking, and Area Deprivation Index (ADI) were obtained from the electronic medical record. These characteristics were compared by PROM-completeness within each pathology group. Comparative analyses between the PROM-complete and PROM-incomplete patients within each pathology group were conducted using the Satterthwaite t-test for continuous variables, Pearson's chi-square test for categorical variables, and Mann-Whitney U test for ordinal variables. Among patients with complete PROMs, availability of PROMIS-Global Health within 2 years pre- and postoperatively was plotted in bins of 84- and 168-days width to characterize the distribution of time points represented in PROM data for these patients. To visualize geographic variation in likelihood of representation in time series PROMs analyses, census block-level heatmaps were generated for each pathology group showing predicted probability of PROM-completeness by logistic regression with age, sex, race, marital status, employment status, insurance category, BMI, and smoking status as predictor variables.

About 4,938 patients (1,751 LSS, 1,711 LSP, 1,476 CSM) were analyzed. PROM-complete patients varied significantly from PROM-incomplete patients in demographic distributions. PROM-complete patients were more likely of White race, married, retired, and less likely to be current smokers. LSS and CSM PROM-complete patients were more likely to have Medicare insurance than PROM-incomplete patients.

Patients completing PROMs for spine surgery may differ from those who do not, with greater representation of White race, being married, retiree status, and Medicare insurance among those with complete PROMs. As PROMs are further incorporated into physician evaluation, value-based reimbursement, and predictive analytics for surgical outcomes, understanding survey nonresponse will be critical for generating equitable, individualized, and informed applications to support healthcare decisions.

To externally validate the PMR impact scale (PMR-IS).

We conducted a prospective cohort study at the University Hospitals Leuven, Leuven, Belgium. Recently diagnosed PMR patients were included between July 2022 and December 2023 and followed until 1 year after diagnosis. All patients completed the PMR-IS, HAQ Disability Index, 36-item Short Form and a visual analogue scale for pain at every visit. Internal consistency, floor and ceiling effects, construct validity, responsiveness and discriminatory power for detecting relapse on the PMR-IS were assessed.

Fifty-five PMR patients (mean age 71 years, 47% female) were included, who had a total of 246 visits. Internal consistency, construct validity and responsiveness met the quality criteria for the symptoms, function and emotional and psychological well-being subdomains. The internal consistency of the glucocorticoid side effects subdomain was insufficient and only one of the three hypotheses for construct validity were met. The function and emotional and psychological well-being subdomains showed a floor effect, while no ceiling effect was observed. The symptoms, function and emotional and psychological well-being subdomains had a good discriminatory power for detecting relapse [area under the curve (AUC) 0.89, 0.86 and 0.72, respectively], but the PMR activity score performed better (AUC 0.94, P < 0.05 for all subdomains).

This study validates the good measurement properties of the symptoms, function and emotional and psychological well-being subdomains of the PMR-IS. In contrast, the glucocorticoid side effects subdomain did not show adequate internal consistency and construct validity, necessitating further validation and possibly refinement of its items prior to application in clinical trials or daily practice.

Background/Objectives: Muscle power, estimated from the sit-to-stand (STS) test, is an important indicator of physical function (PF) in aging adults. Therefore, its assessment may be implemented into future clinical practice. The agreement between different STS power assessments is unknown, and the associations between methods and PF outcomes have not been compared. Methods: A total of 49 aging adults (mean age = 60.9 ± 10.9; 67% female) participated in this cross-sectional study. STS power from a validated equation (EQ) and a linear position transducer (LPT) were estimated. Handgrip strength (HGS), timed up-and-go (TUG), usual gait speed (UGS), fast gait speed (FGS), the 400-m walk test (400MWT), and self-reported total, basic lower-body, and advanced lower-body PF were assessed. The agreement of STS power methods was assessed with an intraclass correlation coefficient (ICC) and a Bland-Altman plot. Multiple linear regression evaluated the associations between STS power and PF outcomes. Results: EQ and LPT STS power demonstrated only moderate agreement (ICC = 0.69). EQ STS power was independently associated with TUG (β = -0.45), UGS (β = 0.37), FGS (β = 0.48), 400MWT (β = -0.55), self-reported total (β = 0.30), basic lower-body (β = 0.30), and advanced lower-body PF (β = 0.30), but not HGS (β = 0.14). LPT STS power was independently associated with HGS (β = 0.44), FGS (β = 0.40), 400MWT (β = -0.51), self-reported total (β = 0.31), basic lower-body (β = 0.29), and advanced lower-body PF (β = 0.32), but neither TUG (β = -0.26) nor UGS (β = 0.28). Conclusions: EQ and LPT STS power demonstrate limited agreement, and EQ STS power may be a superior indicator of PF in aging adults. Future research should examine the feasibility of implementing STS power tests in clinical settings to screen and refer patients with low muscle power to effective therapeutic interventions.

Information about a medicine published in the Summary of Product Characteristics (SmPC) and the product's package leaflet by the European Medicines Agency (EMA) is key to communicate its value to prescribers and patients. The aim of this study was to examine the inclusion of statements related to patient-reported outcomes (PROs) in these documents to communicate patients' perspectives and experiences of new nononcology medicines.

Nononcology therapeutic indications recommended for approval by the EMA between 2018-2022 were identified. The Public Assessment Report(s) (PAR), SmPC, and package leaflet published for each indication were examined. Information about the indication and characteristics relating to how the PROs were assessed in confirmatory studies was extracted.

Most nononcology therapeutic indications (n = 98/140, 70%) contained PRO trial data but less than 50% (n = 64/140, 46%) had PRO-related statements in the SmPC and/or package leaflet. Most statements described treatment benefit (n = 60/64, 94%). Statements were most likely to be included in the SmPC and/or package leaflet if supported by at least 1 randomized controlled trial (n = 52/71, 73%), the endpoint assessed patient-reported symptoms or symptom burden (n = 56/71, 79%), and/or the PRO(s) were assessed as a primary endpoint (n = 24/24, 100%).

Although trial data pertaining to PROs are reviewed when evaluating nononcology drugs, shortfalls persist in the inclusion of PROs when describing treatment benefit in critical documents used to inform treatment decision-making.

Item response theory (IRT) models are an increasingly popular method choice for evaluating clinical outcome assessments (COAs) for use in clinical trials. Given common constraints in clinical trial design, such as limits on sample size and assessment lengths, the current study aimed to examine the appropriateness of commonly used polytomous IRT models, specifically the graded response model (GRM) and partial credit model (PCM), in the context of how they are frequently used for psychometric evaluation of COAs in clinical trials.

Data were simulated under varying sample sizes, measure lengths, response category numbers, and slope strengths, as well as under conditions that violated some model assumptions, namely, unidimensionality and equality of item slopes. Model fit, detection of item local dependence, and detection of item misfit were all examined to identify conditions where one model may be preferable or results may contain a degree of bias.

For unidimensional item sets and equal item slopes, the PCM and GRM performed similarly, and GRM performance remained consistent as slope variability increased. For not-unidimensional item sets, the PCM was somewhat more sensitive to this unidimensionality violation. Looking across conditions, the PCM did not demonstrate a clear advantage over the GRM for small sample sizes or shorter measure lengths.

Overall, the GRM and the PCM each demonstrated advantages and disadvantages depending on underlying data conditions and the model outcome investigated. We recommend careful consideration of the known, or expected, data characteristics when choosing a model and interpreting its results.

Patient-reported outcomes (PROs) assessments arguably provide the most accurate description of the patient experience, as they are directly derived from the patient without the filter of a provider. Utilizing instruments to assess PROs in radiation oncology enables a provider to measure pretreatment, on-treatment, and posttreatment symptoms. In the clinic, PROs are supplemental to physician-derived ratings that help create a complete clinical picture of a patient at a given time point to inform shared decision-making. A compilation of PROs that arise within trials, specific for given treatment regimes, will be invaluable for patients faced with choosing between options.

Tumours of the appendix - a vestigial digestive organ attached to the colon - are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity - wherein the potential misclassification of appendiceal tumours as malignancies of the colon and ovaries also increases. Notwithstanding these diagnostic difficulties, our understanding of appendix carcinogenesis has advanced in recent years. However, there persist considerable challenges to accelerating the pace of research discoveries towards the path to improved treatments and cures for patients with this group of orphan malignancies. The premise of this Expert Recommendation article is to discuss the current state of the field, to delineate unique challenges for the study of appendiceal tumours, and to propose key priority research areas that will deliver a more complete picture of appendix carcinogenesis and metastasis. The Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation Scientific Think Tank delivered a consensus of core research priorities for appendiceal tumours that are poised to be ground-breaking and transformative for scientific discovery and innovation. On the basis of these six research areas, here, we define the first 'cells to society' research framework for appendix tumours.

Rare diseases affect over 400 million people worldwide, with approved treatment available for less than 6 % of these diseases. Drug repurposing is a key strategy in the development of therapies for rare disease patients with large unmet medical needs. The process of repurposing drugs compared to novel drug development is a time-saving and cost-efficient method potentially resulting in higher success rates. To accelerate and ensure sustainability in therapy development for rare neurometabolic, neurological, and neuromuscular diseases, an international consortium SIMilarities in clinical and molecular PATHology (SIMPATHIC) has been established where we move away from the one drug one disease concept and move towards one drug targeting a pathomechanism shared between diseases, by applying parallel preclinical and clinical drug development. Here the consortium describes accelerators of drug repurposing pursued by the consortium, including 1) co-creation, 2) patient empowerment, 3) use of standardized induced pluripotent stem cell (iPSC)-derived disease models and cellular and molecular profiling, 4) high-throughput drug screening in neurons, 5) innovative clinical trial design, and 6) selection of appropriate exploitation and patient access models. In this way, a fast and effective drug repurposing pathway for several rare diseases will be established to reduce time from discovery to patient access.

Non-small cell lung cancer (NSCLC) remains a highly symptomatic with a rapidly increasing incidence. The treatment options are for most patients limited to adjuvant immunotherapy and best supportive care. Therefore, patient-reported outcomes (PROs) are increasingly becoming an essential component in evaluating healthcare quality from the patient's perspective.

We aimed to assess differences in the use of PROs measurement tools and their reporting quality in NSCLC randomized controlled trials (RCTs).

We searched for reports of PROs in NSCLC RCT studies in PubMed, Embase, Web of Science, and Scopus before June 6, 2024. The quality of PRO reporting was assessed using criteria recommended by the International Society for Quality-of-Life Research. Multivariate linear regression was performed to examine the relationship between report quality and influencing factors.

A total of 252 RCTs were included in the analysis, with 23% of these studies reporting PROs as primary endpoints. Overall, studies with PROs as primary endpoints demonstrated higher adherence to the reporting checklist (76%). The results of multivariate linear regression indicated a significant improvement in PRO reporting quality over time (β = 5.35, 95% CI [1.05, 9.64], p < 0.05). However, substantial shortcomings were identified in PRO reporting, including incomplete reporting of missing data and a lack of details on PRO data management modes (e.g., telephone, computer, etc.).

The deficiencies observed in PRO reporting underscore the need for improved design and implementation of PRO endpoints in future NSCLC trials. Enhancing the quality of PRO reporting could improve the relevance and applicability of research findings to clinical practice.

Health-related quality of life (HRQoL) in pulmonary arterial hypertension (PAH) is valued as an outcome measure by patients, clinicians and regulators. The selection of patient-reported outcome measures (PROMs) for measurement of HRQoL in PAH clinical trials lacks systematic evaluation of their suitability, accuracy and reliability.

We report a systematic review (PROSPERO ID: CRD42024484021) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of PROMs selected in PAH clinical trials. PROM measurement properties were then evaluated according to the 10-step COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and graded by recommendation for use. Finally, HRQoL was modelled into a conceptual framework using patient interviews and surveys.

Screening of 896 records identified 90 randomised controlled trials. 43 trials selected PROMs, of which 20 were sufficiently validated to detect meaningful change. Of these, eight trials were adequately powered, using either EuroQol-five dimensions-five levels (EQ-5D-5L), Short-Form-36 (SF-36) or the Living with Pulmonary Hypertension Questionnaire (LPHQ). The COSMIN evaluation recommended EmPHasis-10 and the LPHQ for use (grade A); whereas, SF-36 and EQ-5D-5L require further study (grade B). A conceptual framework of HRQoL was developed from literature comprising 8045 patients. This framework can be used to visualise the different HRQoL concepts measured by different PROMs.

To improve patient-centred research, greater consistency in PROM selection is required. Three of 90 randomised controlled trials have selected COSMIN-recommended PROMs. Whilst the PROMs evaluated require development across the 10 areas of psychometric property measurement, EmPHasis-10 and the LPHQ can be recommended for use. The ratified conceptual framework can further support PROM selection by identifying the HRQoL concepts they are likely to capture.

The Global Leadership Initiative in Sarcopenia (GLIS) aims to standardize the definition and diagnostic criteria for sarcopenia into one unifying, common classification. Among other actions to achieve this objective, the GLIS has organized three different working groups (WGs), with the WG on outcomes of sarcopenia focusing on reporting its health outcomes to be measured in clinical practice once a diagnosis has been established. This includes sarcopenia definitions that better predict health outcomes, the preferred tools for measuring these outcomes, and the cutoffs defining normal and abnormal values. The present article synthesizes discussions and conclusions from this WG, composed of 13 key opinion leaders from different continents worldwide. Results rely on systematic reviews, meta-analyses, and relevant cohort studies in the field. With a high level of evidence, sarcopenia is significantly associated with a reduced quality of life, a higher risk of falls and fractures and a higher risk of mortality. Sarcopenia has been moderately associated with a higher risk of reduced instrumental activities of daily living (IADL). However, the GLIS WG found only inconclusive level of evidence to support associations between sarcopenia and higher risks of hospitalization, nursing home admission, mobility impairments, and reduced basic activities of daily living (ADL). This limitation underscores the scarcity of longitudinal studies, highlighting a barrier to understanding its progression and implications over time.

Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).

To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.

A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.

Patients with rCDI had poor HRQoL, which improved following FMT.

Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.

The rarity of capitellum fractures makes them a thorny problem in orthopedic practice, as fracture reduction and repair to restore joint function within a complex elbow joint are difficult. Properly treated, these fractures can avoid complications such as stiffness, instability, and posttraumatic arthritis. Several surgical techniques optimize patient outcomes, including open reduction with internal fixation using Herbert screws, buttress plating, and headless compression screws (HCS). The choice of technique, however, is determined by many factors, including fracture type, patient characteristics, and surgeon preference. This systematic review compares the clinical and functional outcomes of surgical techniques for capitellar fracture repair. Factors influencing the selection of surgical approach are also reviewed, including fracture complexity, patient demographics, and bone quality. To perform a systematic literature search, we followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched the major databases, including PubMed, Cochrane Library, Embase, and Web of Science. Search terms included "capitellar fracture", "elbow fracture", and "surgical fixation techniques". Clinical or biomechanical outcomes of capitellar fracture fixation using different surgical techniques were included, including fixation stability, range of motion, healing rates, and complication rates. In detail, three foundational studies were analyzed in depth, with the use of Herbert screws, Kirschner wires, and buttress plating. Clinical trials suggest that Herbert screws enable earlier mobilization and improved functional outcomes, particularly in younger patients with Type I fractures. Biomechanical studies, such as those using HCS with buttress plating, indicate enhanced stability, especially in osteoporotic bone conditions. Factors such as patient age, bone quality, and fracture pattern appear to influence the choice of surgical technique. Herbert screws provide effective fixation and support early mobilization, making them suitable for stable fractures in healthier patients. However, in cases of osteoporotic or complex fractures, augmented techniques, such as buttress plating, may be more appropriate to improve stability and reduce the risk of fixation failure. The selection of surgical techniques for capitellar fractures should take into account patient-specific factors to optimize clinical outcomes, and this review emphasizes the need for a tailored approach in selecting surgical techniques for capitellar fractures.

Periodontal diseases could cause halitosis and may impair taste and smell. While non-surgical periodontal therapy is known to reduce halitosis, its effects on taste and smell are less studied. This study aims to investigate the factors influencing self-perceived halitosis, taste, and smell, as well as the changes in these perceptions after periodontal therapy.

A total of 183 participants were divided into three groups: 61 patients with periodontitis, 61 with gingivitis, and 61 who were gingivally healthy. Periodontal parameters and self-perceived halitosis, taste, and smell were evaluated at baseline and four weeks after non-surgical periodontal treatment using a visual analog scale (VAS). Robust regression analysis was used to assess independent variables influencing baseline VAS ratings.

The periodontitis group had the lowest taste perception and the highest self-perceived halitosis scores (p < 0.05). Taste perception was negatively associated with ≥ 4 mm pockets (p = 0.002). A positive relationship was also observed between the plaque index and self-perceived halitosis (p = 0.030). Post-treatment, taste perception improved significantly in all groups (p < 0.05), in parallel with improvements in periodontal parameters. Additionally, self-perceived halitosis showed a significant decrease (p < 0.05). The improvement in smell perception was statistically significant in the gingivally healthy and periodontitis groups (p < 0.05).

Periodontal disease may contribute to the development of chemosensory disorders. While the main goal of periodontal treatment is disease management, it can also improve taste and smell function. Oral hygiene practices play an essential role in the development of these improvements. However, further research is needed on the subject.

The study was registered as "Investigation of Halitosis, Taste, and Smell in Terms of Periodontal Condition Stated by Patients and Periodontal Diagnosis by Dentists, and Then Evaluation of Change Before and After Treatment" with the registration number NCT06063460 (13/09/2023) at https://www.

gov Protocol Registration and Results System.

This clinical trial was registered prior to participant recruitment on ClinicalTrials.gov (NCT06063460,13.09.2023).

Virtual reality (VR) has promise as an innovative nonpharmacologic treatment for improving a patient's quality of life. VR can be used as an adjunct or treatment for many acute and chronic conditions, including serious illnesses.

This systematic review aims to assess the current state of the literature of randomized controlled trials that use VR in patients with serious illnesses. Two secondary aims include assessing intervention components associated with improved quality of life and functional outcomes among older adults, as well as evaluating how well the randomized controlled trials adhere to consensus standards for VR research.

We searched PubMed, Embase, and CINAHL for randomized controlled studies published at any time. We screened and accepted studies that reported outcomes related to patients' quality of life, provided an immersive VR intervention, and included patients with serious illness. We narratively summarized key attributes of publications that shed light on study efficacy, generalizability, replicability, and clinical utility. All studies were assessed for study quality with the Cochrane Risk of Bias tool and for concordance with 8 recent consensus standards for VR research.

From the 12,621 articles searched in May 2024, a total of 24 (0.19%) studies met the inclusion criteria, and of these, 88% (21/24) reported an improvement in at least 1 patient quality of life outcome and 67% (16/24) had a high risk of bias. In 7 (n=24, 29%) studies, VR was used to provide distraction therapy to reduce pain. In total, 5 (n=24, 21%) studies included training, supervision, and assistance in VR use, which demonstrated improvements in patient quality of life-related outcomes. Of 24 studies, 9 (38%) included patients with stroke, 9 (38%) included patients with cancer, 4 (17%) included patients with cardiovascular disease, 1 (4%) included patients with chronic obstructive pulmonary disease, and 1 (4%) included patients who reported pain in hospital. In all 9 studies that included patients with stroke, the main purpose of VR was to improve mobility and strength; these studies had higher frequency and longer durations of VR use, ranging from 2 to 9 weeks, as compared to a VR use duration of <2 weeks for studies aiming to reduce pain or anxiety. Regarding consensus standards for VR research, 29% (7/24) of the studies adhered to all 8 criteria, and all studies (24/24, 100%) adhered to ≥5 criteria.

Nascent evidence suggests VR's potential in mitigating pain, anxiety, and depression and improving mobility among persons with serious illnesses. Most studies did not provide detailed information about unassisted or assisted use, suggesting that VR for older adults is currently most appropriate for observed settings with assistance available.

PROSPERO CRD42022346178; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346178.

Guillain-Barré syndrome (GBS) is an autoimmune neurological disorder characterized by muscle weakness. In clinical trials, treatment benefit and disease severity are typically measured using clinician-reported outcome measures like the Hughes Functional Grading Scale (HFGS). However, patient-reported outcome measures, such as the Rasch-built Overall Disability Scale (R-ODS) may provide additional insight into the patient experience during treatment. In this study, exploratory analyses of clinical trial data were performed to investigate how existing clinician-reported outcomes and patient-reported outcomes can help to assess disease progression by providing an accurate measurement of functional status.

Data were collected as part of a phase 3 study to assess the safety and efficacy of eculizumab in patients in Japan with severe GBS. The association between HFGS score and R-ODS total centile score (linear measure of limitations; 0, most severe activity and social participation limitations and 100, no limitations) was assessed using the Spearman rank-order correlation coefficient. Threshold values of R-ODS total centile score that could differentiate between patients with an HFGS score of ≤ 1 and > 1 were determined using receiver-operating characteristic curve analyses and mapping (Rasch measurement theory). A triangulation approach was used to establish a proposed value for R-ODS total centile score equivalent to an HFGS score of ≤ 1 or > 1.

Overall, 57 patients were included in this analysis. These exploratory analyses revealed good correlation between R-ODS total centile and HFGS scores. Using the Rasch model, mapping of HFGS to R-ODS scores showed a good fit. Evaluation of the R-ODS threshold that could approximate the functional motor symptom categories based on HFGS (score of 0 or 1) revealed a range of values from 60 to 80. Based on a trial sample, a threshold of 60 was found to have 100% sensitivity and 87% specificity at week 4, and 93.8% sensitivity and 77.8% specificity at week 24.

This study established thresholds for the R-ODS total centile score that could approximate classification of functional impairment in GBS based on the HFGS score. Given that the R-ODS reflects the patient perspective, it may be used to capture a more complete picture of GBS severity.

There is evidence of low completion of patient-reported outcome measures (PROMs) by people from culturally and linguistically diverse (CALD) backgrounds and Indigenous Peoples with chronic health conditions. We aimed to systematically identify ways to support and promote PROM completion by CALD communities and Indigenous Peoples in clinical care settings.

We searched Medline, Embase, Scopus, Web of Science Core Collections and CINAHL databases from 1 January 2000 to 19 September 2024. Primary studies were included if they focused on ways to support and promote PROM completion in the care of CALD and Indigenous populations in clinical care settings. The quality of the included papers was appraised independently by two reviewers, using the Critical Appraisal Skills Programme (CASP) and Mixed Methods Appraisal Tool (MMAT). Data were analysed thematically. PROSPERO registration: CRD42023469317.

Of 13,450 title/abstracts retrieved, five papers met eligibility. Strategies to promote PROM completion by Indigenous Peoples included (1) providing training to patients about what PROMs are (2) offering verbal modes of completion and (3) community consultation during design, development, and implementation of PROMs to ensure culturally appropriate and sensitive PROMs are used. Strategies to promote completion by people who are CALD included (1) providing information about how to use electronic PROMs, (2) facilitating self-completion, (3) offering different modes of completion (paper-based, digital), (4) increasing availability of culturally and linguistically appropriate PROM translations, and (5) system-wide financial and administrative support to use translated PROMs.

Few studies reported strategies to support the completion of PROMs by people from CALD backgrounds and/or Indigenous Peoples. Adequate training, planning (including community consultation), resourcing, and financial support are required to encourage people who are CALD and Indigenous Peoples to participate in PROM initiatives globally.

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance in gastrointestinal cancers (GI), particularly through the pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth and reshape the TME, creating conditions such as nutrient depletion, hypoxia, and acidity that impair antitumor immune responses. Immune cells within the TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes that promote tumor progression and reduce the efficacy of therapies. The competition for essential nutrients, particularly glucose, between cancer and immune cells compromises the antitumor functions of effector immune cells, such as T cells. Additionally, metabolic by-products like lactate and kynurenine further suppress immune activity and promote immunosuppressive populations, including regulatory T cells and M2 macrophages. Targeting metabolic pathways such as fatty acid oxidation and glycolysis presents new opportunities to overcome drug resistance and improve therapeutic outcomes in GI cancers. Modulating these key pathways has the potential to reinvigorate exhausted immune cells, shift immunosuppressive cells toward antitumor phenotypes, and enhance the effectiveness of immunotherapies and other treatments. Future strategies will require continued research into TME metabolism, the development of novel metabolic inhibitors, and clinical trials evaluating combination therapies. Identifying and validating metabolic biomarkers will also be crucial for patient stratification and treatment monitoring. Insights into metabolic reprogramming in GI cancers may have broader implications across multiple cancer types, offering new avenues for improving cancer treatment.

Sensor-based digital health technologies (sDHTs) are increasingly used to support scientific and clinical decision-making. The digital clinical measures they generate offer enormous benefits, including providing more patient-relevant data, improving patient access, reducing costs, and driving inclusion across health care ecosystems. Scientific best practices and regulatory guidance now provide clear direction to investigators seeking to evaluate sDHTs for use in different contexts. However, the quality of the evidence reported for analytical validation of sDHTs-evaluation of algorithms converting sample-level sensor data into a measure that is clinically interpretable-is inconsistent and too often insufficient to support a particular digital measure as fit-for-purpose. We propose a hierarchical framework to address challenges related to selecting the most appropriate reference measure for conducting analytical validation and codify best practices and an approach that will help capture the greatest value of sDHTs for public health, patient care, and medical product development.

Advanced therapy medicinal products (ATMPs) are medicines based on genes, tissues, or cells and can include gene therapy, somatic-cell therapy, and tissue-engineered medicines. Patient-reported outcomes (PROs) are reports on health and well-being that come directly from the individual without external interpretation. Patient-reported outcome measures (PROMs) are questionnaires aimed at assessing the individual and subjective experience with health and other psychosocial aspects. The aim of the present review is to assess the extent and quality of PROs and PROMs used in orphan ATMP trials.

The database from National Health Service Special Pharmacy Service horizon scanning was searched on 27 March 2024 to identify all ATMPs for orphan conditions. Clinical trial protocols were included in this review if they investigated ATMPs for orphan conditions and were published in clinical trial databases.

A total of 100 trials were included. These accounted for 64 conditions. Only 37% (37/100) of the trials included PROs. Overall, 17 different types of PROs were identified across the trials. Quality of life (QoL) and health-related quality of life (HRQoL) were the most frequent PROs found in 18% (18/100) and 13% (13/100) of the trials, respectively. A total of 33 PROMs were identified. Of these, 57% (19/33) were HRQoL (89% [17/19]) or QoL (11% [2/19]) measures. Of the HRQoL measures identified, 71% (12/17) were disease specific and 29% (5/17) were generic. Of the non-QoL PROMs, 29% (4/14) were designed to measure pain and 71% (10/14) PROMs focused on other psychological outcomes, including anxiety and depression.

Our results show that only 37% of the orphan ATMP trials include patient-reported outcomes and measures. This highlights the urgent need for relevant PROs/PROMs that capture benefits and harms and assimilation of existing PROMs for better comparison between or within conditions. It is essential to include and reflect the patients' experience so that those intended to benefit from the research have the opportunity to influence its direction.

Patient-reported outcomes (PROs) can provide useful insights into patient perception of concizumab, an anti-tissue factor pathway inhibitor monoclonal antibody intended for once-daily, subcutaneous prophylaxis for hemophilia A (HA) or hemophilia B (HB), with and without inhibitors.

To evaluate PROs from the phase 3 explorer8 study (NCT04082429).

Male patients aged ≥12 years with HA/HB without inhibitors were enrolled and randomized 1:2 to no prophylaxis/on-demand treatment (arm 1) or concizumab prophylaxis (arm 2) or allocated to concizumab prophylaxis (arms 3 and 4). PRO questionnaires included the 36-item short-form health survey version 2, Haemophilia Quality of Life Questionnaire for Adults, Hemophilia Treatment Experience Measure, and Haemophilia Patient Preference Questionnaire.

Estimated treatment difference for change in 36-item short-form health survey version 2 "bodily pain" and "physical functioning" from baseline to week 24 between patients in arms 1 and 2 was 9.5 points (95% CI, 2.4 to 16.7) and 0.3 points (95% CI, -5.1 to 5.6), respectively. Estimated treatment difference at week 24 between patients in arms 1 and 2 was -18.0 points (95% CI, -26.4 to -9.5) for Haemophilia Quality of Life Questionnaire for Adults "total score" and -16.8 points (95% CI, -32.2 to -1.4) for "physical health." Hemophilia Treatment Experience Measure and Haemophilia Patient Preference Questionnaire results favored concizumab prophylaxis over no prophylaxis or previous treatment.

PRO data from the phase 3 explorer8 study provided additional support for concizumab prophylaxis compared with no prophylaxis as a treatment option for patients with HA/HB.