ATF1 promotes ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2.

BACKGROUND: Ferroptotic proteins are promising therapeutic targets for lung cancer. The PROM2 is upregulated in lung cancer and known to suppress ferroptosis. This study examined the molecular mechanisms for PROM2-induced ferroptosis resistance in lung cancer. METHODS: Ferroptosis in lung cancer was assessed by iron kit, and transmission electron microscopy was applied to observe the changes in mitochondrial morphology. BODIPY™ was applied to test the lipid ROS, and MeRIP was performed to test the m6A modification of PROM2. RIP assay was employed for confirming the binding between METTL3 and PROM2. In addition, dual luciferase assay was employed for exploring the transcriptional regulation of ATF1 to METTL3, and the binding relation between ATF1 and METTL3 promoter region was explored by ChIP assay. RESULTS: Expression levels of PROM2 were significantly higher in lung cancer cell lines than a noncancerous control line, and PROM2 knockdown significantly reduced both cancer cell viability and proliferation rate. In addition, PROM2 knockdown reduced xenograft tumor growth and exacerbated erastin-induced ferroptosis. Compared to PROM2 mRNA from control cells, transcripts in lung cancer cells exhibited enhanced m6A levels, and showed greater binding with METTL3. Further, ATF1 upregulated METTL3 transcription, thereby stabilizing PROM2 mRNA and increasing ferroptosis resistance. CONCLUSION: ATF1 could promote ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2. Thus, our work might shed novel insights on discovering therapeutic strategy for lung cancer.

Patient-Reported Outcome Measures for Patients With CKD: The Case for Patient-Reported Outcomes Measurement Information System (PROMIS) Tools.

Chronic kidney disease (CKD), kidney failure, and kidney replacement therapies are associated with high symptom burden and impaired health-related quality of life (HRQOL). Symptoms change with disease progression or transition between treatment modalities and frequently go unreported and unmanaged. Tools that reliably monitor symptoms may improve the management of patients with CKD. Patient-reported outcome measures (PROMs) assess symptom severity; physical, psychological, social, and cognitive functioning; treatment-related side effects; and HRQOL. Systematic use of PROMs can improve patient-provider communication, patient satisfaction, clinical outcomes, and HRQOL. Potential barriers to their use include a lack of engagement, response burden, and limited guidance about PROM collection, score interpretation, and workflow integration. Well-defined, acceptable, and effective clinical response pathways are essential for implementing PROMs. PROMs developed by the Patient-Reported Outcomes Measurement Information System (PROMIS) address some challenges and may be suitable for clinical use among patients with CKD. PROMIS tools assess multiple patient-valued, clinically actionable symptoms and functions. They can be administered as fixed-length, customized short forms or computer adaptive tests, offering precise measurement across a range of symptom severities or function levels, tailored questions to individuals, and reduced question burden. Here we provide an overview of the potential use of PROMs in CKD care, with a focus on PROMIS.

Effect of Bimekizumab on Patient-Reported Disease Impact in Patients with Psoriatic Arthritis: 1-Year Results from Two Phase 3 Studies.

OBJECTIVES: To evaluate 1-year bimekizumab efficacy in psoriatic arthritis (PsA) from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. METHODS: BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to tumour necrosis factor inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to week 40 in BE COMPLETE). RESULTS: Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at week 4 continued to week 16 and were sustained to 1 year. At 1 year, mean (standard error) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at week 16 (bDMARD-naïve bimekizumab -2.3 [0.1], placebo/bimekizumab -2.2 [0.1]; TNFi-IR bimekizumab -|2.5 [0.1], placebo/bimekizumab -2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems. CONCLUSION: Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA.

Long-term patient-reported outcomes among patients undergoing revascularization vs medical therapy for intermittent claudication.

OBJECTIVE: Society for Vascular Surgery guidelines recommend revascularization for patients with intermittent claudication (IC) if it can improve patient function and quality of life. However, it is still unclear if patients with IC achieve a significant functional benefit from surgery compared with medical management alone. This study examines the relationship between IC treatment modality (operative vs nonoperative optimal medical management) and patient-reported outcomes for physical function (PROMIS-PF) and satisfaction in social roles and activities (PROMIS-SA). METHODS: We identified patients with IC who presented for index evaluation in a vascular surgery clinic at an academic medical center between 2016 and 2021. Patients were stratified based on whether they underwent a revascularization procedure during follow-up vs continued nonoperative management with medication and recommended exercise therapy. We used linear mixed-effect models to assess the relationship between treatment modality and PROMIS-PF, PROMIS-SA, and ankle-brachial index (ABI) over time, clustering among repeat patient observations. Models were adjusted for age, sex, diabetes, Charlson Comorbidity Index, Clinical Frailty Score, tobacco use, and index ABI. RESULTS: A total of 225 patients with IC were identified, of which 40% (n = 89) underwent revascularization procedures (42% bypass; 58% peripheral vascular intervention) and 60% (n = 136) continued nonoperative management. Patients were followed up to 6.9 years, with an average follow-up of 5.2 ± 1.6 years. Patients who underwent revascularization were more likely to be clinically frail (P = .03), have a lower index ABI (0.55 ± 0.24 vs 0.72 ± 0.28; P < .001), and lower baseline PROMIS-PF score (36.72 ± 8.2 vs 40.40 ± 6.73; P = .01). There were no differences in patient demographics or medications between treatment groups. Examining patient-reported outcome trends over time; there were no significant differences in PROMIS-PF between groups, trends over time, or group differences over time after adjusting for covariates (P = .07, P = .13, and P =.08, respectively). However, all patients with IC significantly increased their PROMIS-SA over time (adjusted P = .019), with patients managed nonoperatively more likely to have an improvement in PROMIS-SA over time than those who underwent revascularization (adjusted P = .045). CONCLUSIONS: Patient-reported outcomes associated with functional status and satisfaction in activities are similar for patients with IC for up to 7 years, irrespective of whether they undergo treatment with revascularization or continue nonoperative management. These findings support conservative long-term management for patients with IC.

Person-reported outcomes in registered randomised diabetes trials: A mapping review of constructs.

AIM: Recently, efforts have been made to use and report person-reported outcomes (PROs) in randomised clinical trials (RCTs). Here, we aim to (1) assess the status of inclusion of PROs in registered RCTs over 5 years in people with type 1 or 2 diabetes, and (2) map the PRO measures (PROMs) onto predefined domains. METHODS: The largest trial registries (Clinicatrials.gov, International Clinical Trial Platform and ISRCTN) were systematically searched for RCTs in people with type 1 and/or type 2 diabetes of all ages between 2018 and 2023. Coding of PROs comprised: (1) PRO measure(s) included yes or no; if yes: (2) PRO(s) as primary outcome yes or no; and (3) mapping PROMs onto predefined PRO domains and per type of intervention. RESULTS: N = 1543 trials met our inclusion criteria, of which n = 673 (44%) included PROs, assessed by 545 different measures. Twenty per cent of drug trials (n = 112) and 71% of behavioural interventions (n = 405) included PROs. In 149 trials (9.6%), a PRO was the primary outcome. The psychological functioning domain was most often assessed across all trials (21.6%), specifically in behavioural (44.8%) and medical device interventions (29.7%). In drug trials, the physical functioning and functional health domain was most included (9%). Across all trials, the social and family functioning domain was least assessed (3%). CONCLUSIONS: We noticed an increase in the inclusion of PROs in diabetes RCTs. However, PROs are rarely included as primary outcomes in the majority of studies, particularly in drug trials. The heterogeneity of PROMs used in RCTs underscores the need for standardisation of PROs.

The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia.

BACKGROUND: Appropriately defining and using the minimal important change (MIC) and the minimal clinically important difference (MCID) are crucial for determining whether the results are clinically significant. The aim of this study is to survey the status of randomized controlled trials (RCTs) for insomnia interventions to assess the inclusion and interpretation of MIC/MCID values. METHODS: We conducted a cross-sectional study to survey the status of RCTs for insomnia interventions to assess the inclusion and appropriate interpretation of MIC/MCID values. A literature search was conducted by searching the main sleep medicine journals indexed in PubMed, the Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify a broad range of search terms. We included RCTs with no restriction on the intervention. The included studies used the Insomnia Severity Index (ISI) or the Pittsburgh Sleep Quality Index (PSQI) questionnaire as the outcome measures. RESULTS: 81 eligible studies were identified, and more than one-third of the included studies used MIC/MCID (n = 31, 38.3%). Among them, 21 studies with ISI as the outcome used MIC defined as a relative decrease ranging from 3 to 8 points. The most frequently used MIC value was a 6-point decrease (n = 7), followed by 8-point (n = 6) and 7-point decrease (n = 4), a 4 to 5-points decrease (n = 3), and a 30% reduction from baseline; 6 studies used MCID values, ranging from 2.8 to 4 points. The most frequently used MCID value was a 4-point decrease in the ISI (n = 4). 4 studies with PSQI as the outcome used a 3-point change as the MIC (n = 2) and a 2.5 to 2.7-point difference as MCID (n = 2). 4 non-inferiority design studies considered interval estimation when drawing clinically significant conclusions in their MCID usage. CONCLUSIONS: The lack of consistent MIC/MCID interpretation and usage in outcome measures for insomnia highlights the urgent need for further efforts to address this issue and improve reporting practices.

What should be next in lifelong posterior hypospadias: Conclusions from the 2023 ERN eUROGEN and EJP-RD networking meeting.

BACKGROUND: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life. AIM: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients. METHODS: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon. RESULTS: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary. CONCLUSIONS: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research.

The development of a cryptoglandular anal fistula quality of life scale (AF-QoL).

AIM: Quality of life (QoL) is a crucial and core outcome in assessing the effectiveness of treatments for cryptoglandular anal fistula. Despite its extensive impact, there is a lack of patient-centred, disease-specific QoL measurement instruments of adequate quality. The aim of this study is to develop a disease-specific measurement instrument that can accurately measure QoL for patients with cryptoglandular anal fistula. METHOD: Semi-structured qualitative patient interviews and a systematic review of current instruments were used to generate items for the draft instrument. This underwent successive rounds of cognitive interviews to refine its wording and structure. Individual item and overall scale content validity were determined by asking experts to rate the relevance of each item and those deemed irrelevant were removed. The final instrument then underwent psychometric testing and test-retest analysis to determine its sensitivity and stability. RESULTS: A total of 148 patients were involved in item generation, scale development and psychometric testing. A 22-item measurement instrument has been developed; it is scored on a scale of 0-100, where 0 indicates the worst QoL and 100 demonstrates perfect QoL. The scale demonstrates excellent internal consistency (Cronbach-α = 0.927), strong content and construct validity [correlation with Perianal Disease Activity Index = -0.713, Hospital Anxiety and Depression Anxiety (-0.659) and Depression (-0.673) subscales and Short Form-12 physical (0.609) and mental (0.589) component scales] and strong reliability and responsiveness. CONCLUSION: We have developed a cryptoglandular Anal Fistula Quality of Life scale (AF-QoL), a comprehensive, disease-specific patient reported outcome measure assessing QoL in patients with cryptoglandular anal fistula.

Malnutrition prevalence in cancer patients in Belgium: The ONCOCARE study.

RATIONALE: Unintentional weight loss and malnutrition are common among cancer patients. Malnutrition has been associated with impaired health-related quality of life, less well-tolerated chemotherapy regimens and shorter life duration. In Belgium there is a lack of epidemiological data on malnutrition in oncology patients at advanced stages of the disease. METHODS: Malnutrition assessment data was collected through a prospective, observational study in 328 patients who started a neoadjuvant anticancer therapy regimen or who started 1st, 2nd or 3rd line anticancer therapy for a metastatic cancer via 3 visits according to regular clinical practice (baseline visit (BV) maximum 4 weeks before start therapy, 1st Follow up visit (FUV1) ± 6 weeks after start therapy, FUV2 ± 4 months after start therapy). Malnutrition screening was evaluated using the Nutritional Risk Screening score 2002 (NRS-2002)and the diagnosis of malnutrition by the GLIM criteria. In addition, SARC-F questionnaire and Fearon criteria were used respectively to screen for sarcopenia and cachexia. RESULTS: Prevalence of malnutrition risk at BV was high: 54.5% of the patients had a NRS ≥ 3 (NRS 2002) and increased during the study period (FUV1: 73.2%, FUV2: 70.1%). Prevalence of malnutrition based on physician subjective assessment (PSA) remained stable over the study period but was much lower compared to NRS results (14.0%-16.5%). At BV, only 10% of the patients got a nutrition plan and 43.9% received ≤ 70% of nutritional needs, percentage increased during FU period (FUV1: 68.4%, FUV2: 67.6%). Prevalence of sarcopenia and cachexia were respectively 12.4% and 38.1% at BV and without significant variation during the study period, but higher than assessed by PSA (11.6% and 6.7% respectively). Figures were also higher compared to PSA. There were modifications in cancer treatment at FUV1 (25.2%) and at FUV2 (50.8%). The main reasons for these modifications at FUV1 were adverse events and tolerability. Patient reported daily questionnaires of food intake showed early nutritional deficits, preceding clinical signs of malnutrition, and therefore can be very useful in the ambulatory setting. CONCLUSIONS: Prevalence of malnutrition and cachexia was high in advanced cancer patients and underestimated by physician assessment. Earlier and rigorous detection of nutritional deficit and adjusted nutritional intake could lead to improved clinical outcomes in cancer patients. Reporting of daily caloric intake by patients was also very helpful with regards to nutritional assessment.

Validation of the brain injury associated visual impairment - impact questionnaire (BIVI-IQ).

PURPOSE: The Brain Injury associated Visual Impairment - Impact Questionnaire (BIVI-IQ) was developed to assess the impact of post-stroke visual impairment. The development of the questionnaire used robust methods involving stroke survivors and clinicians. The aim of this study was to assess the validity of the BIVI-IQ in a stroke population. METHODS: Stroke survivors with visual impairment were recruited from stroke units, outpatient clinics and non-healthcare settings. Participants were asked to complete questionnaire sets on three separate occasions; the BIVI-IQ at each visit with additional questionnaires at baseline and visit 2. Vision assessment and anchor questions from participants and clinicians were collected. The analysis included assessment of missing data, acceptability, Rasch model analysis, test-retest reliability, construct validity (NEI VFQ-25, EQ-5D-5L) and responsiveness to change. RESULTS: 316 stroke survivors completed at least one questionnaire of the 326 recruited. Mean age was 67 years and 64% were male. Adequate fit statistics to the Rasch model were reached (χ2 = 73.12, p = 0.02) with two items removed and thresholds of two adjusted, indicating validity and unidimensionality. Excellent test-retest reliability was demonstrated (ICC = 0.905) with a 3-month interval. Construct validity was demonstrated with a strong significant correlation to the NEI VFQ-25 (r = 0.837, p < 0.01). The BIVI-IQ also demonstrated responsiveness to change with significant differences identified between groups based on participant and clinician anchor questions (X2 = 23.29, p < 0.001; X2 = 24.56, p < 0.001). CONCLUSION: The BIVI-IQ has been shown to be valid and practical for 'everyday' use by clinicians and researchers to monitor vision-related quality of life in stroke survivors with visual impairment.

A Real-World Study of Nusinersen Effects in Adults with Spinal Muscular Atrophy Type 2 and 3.

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive genetic disorder characterized by muscle weakness ultimately leading to pulmonary impairments that can be fatal. The recent approval of nusinersen, a disease-modifying therapy, substantially changed the prognosis for patients, particularly in children. However, real-world evidence about its long-term effectiveness in adults remains limited. This study aimed to document longitudinal data on motor function, pulmonary function and patient-reported outcome measures of Canadian adults with SMA type 2 and 3 treated with nusinersen. METHODS: Outcomes from 17 patients were collected at the Institut de réadaptation en déficience physique de Québec during routine clinical visits over 36 months post nusinersen treatment, using the Hammersmith Functional Motor Scale Expanded for SMA (HFMSE), Revised Upper Limb Module (RULM), 6-Minute Walk Test (6MWT), Children's Hospital of Philadelphia Adult Test of Neuromuscular Disorders (CHOP-ATEND), SMA functional rating scale (SMAFRS), pulmonary function testing and subjective changes reported by patients. RESULTS: After 36 months, 9 patients showed motor function improvement. Changes beyond the minimal clinically important difference were seen for four patients on the HFMSE, four patients on the RULM and five patients on the 6MWT. Pulmonary function remained stable for most subjects. Subjective positive changes were reported in 88% of patients and five patients showed improvement in the SMAFRS. CONCLUSION: This real-world study demonstrates the positive effects of nusinersen in adults with SMA types 2 and 3. Although stabilizing the patient's condition is considered therapeutic success, this study shows an improvement in motor function and subjective gains in several patients.

Patient adherence and response time in electronic patient-reported outcomes: insights from three longitudinal clinical trials.

PURPOSE: Patient-reported outcome measures (PROMs) are used to collect data on disease symptoms in support of clinical trial endpoints. Clinical studies can last a year or more, and the patients' adherence and response time to daily at-home questionnaires may vary significantly over time. The aim of this study was to understand patterns and changes in patients' completion of daily PROMs during longitudinal clinical studies. METHODS: Data were collected from 1342 patients randomized into three respiratory clinical trials (NCT03401229, NCT03347279, and NCT03406078). PROMs were completed by patients using electronic handheld devices that collected the starting and completion times. A Bayesian generalized linear mixed-effects model was used to identify unbiased coefficients associated with PROM adherence and response time using patient, site, and calendar features as covariates. RESULTS: Adherence decreased over time after randomization, and the rate of decrease was higher in younger patients. The 14-day pre-randomization adherence was correlated with adherence throughout the study. Patients were also more adherent during working days compared to non-working days. Oldest patients took twice as long to complete PROMs throughout the study; however, the response time for all patients decreased during the first month of the study regardless of age. Response time increased 7 days before and after the date of a scheduled clinic visit and when a patient-reported higher symptom burden. CONCLUSION: Detailed analyses of adherence and response time for daily PROMs in clinical trials can provide significant insights about trends of patient behavior in longitudinal clinical studies with high baseline adherence.

Psychoeducational group interventions for adults diagnosed with attention-deficit/ hyperactivity disorder: a scoping review of feasibility, acceptability, and outcome measures.

INTRODUCTION: Although psychoeducational group interventions are increasingly used for adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), a comprehensive review focused on the feasibility and acceptability indicators of these interventions remains lacking. Furthermore, although previous research has explored various aspects of psychoeducation for ADHD, such as its definition and approaches, limited research has focused on the synthesis for outcome measures and patients' experiences related to these interventions. Therefore, this scoping review aims to map the existing evidence reported on psychoeducational group interventions for adults diagnosed with ADHD. The objective is to provide a comprehensive overview of feasibility indicators, acceptability, and outcome measures used in psychoeducational group interventions. METHOD: A comprehensive structured literature search on the topic was performed in seven bibliographic databases, and the resulting records were independently screened, and their data extracted by two reviewers. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-S) to ensure the transparency and rigor of this scoping review. RESULTS: The searches yielded 7510 records. Eight studies met the inclusion criteria. These included studies were conducted in European countries and the United States. Among these, six studies used a randomized control design, one an open feasibility trial, and one a pre-post intervention design. All the studies reported some feasibility and acceptability indicators. While all the studies reported on the severity of symptoms of ADHD as an outcome measure, some also reported on outcomes related to psychological or mental-health problems, quality of life, changes in knowledge regarding ADHD, or the level of self-esteem, functioning, and impairment. CONCLUSION: This scoping review revealed that psychoeducational group interventions are generally acceptable for patients in terms of patient satisfaction with the group intervention. All included studies reported some feasibility indicators, with some reporting good attendance and relatively low dropout rates. Most studies reported positive effects on ADHD and mental health symptoms, suggesting that these interventions are beneficial for adults with ADHD. However, several gaps exist regarding the reporting on the feasibility indicators, acceptability, and outcome measures employed across studies.

Text message questionnaires for Patient-Reported Outcome Measures after Cesarean section-A feasibility study.

BACKGROUND: Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed assessment on the timing of severe pain, opioid consumption, influence on activities such as mobilization, breastfeeding, and caring for the infant are difficult to conduct, especially after discharge. Short message services (SMS)-based questionnaires may offer a low-cost way of providing such data but with the risk of insufficient response rates. We assessed the feasibility of collecting detailed, prospective data on postoperative pain and recovery during the initial hours and days following cesarean section using SMS-based questionnaires. METHODS: Prospective Danish single-center cohort study involving elective cesarean sections under spinal anesthesia with fentanyl and bupivacaine. The postoperative pain regimen consisted of paracetamol, NSAID and oral morphine by request. Patients received an SMS-based questionnaire at 6, 12, 18, 24, and 48 h postoperatively, as well as on days 7 and 30. PRIMARY OUTCOME: Response rate and time from receiving the SMS to completion of the questionnaires. SECONDARY OUTCOMES: Opioid consumption and Patient Reported Outcomes Measures on pain and recovery. RESULTS: From December 2022 to June 2023; 100 patients were included. The response rate was 78% at 6 h postoperatively, decreasing to 63% at 24 h. The median response time from receiving to answering the SMS-based questionnaire at 6 h after cesarean section was 23 min (IQR 2-72), decreasing to 20 min (IQR 2-78) after 24 h. Severe pain, corresponding to a Numeric Rating Scale (NRS) score >6, was reported by 57% (95% CI 65-84) at 6 h, decreasing to 28% (95% CI 34-58) at 24 h. Median opioid consumption within the first 24 h was 30 mg (IQR 20-50). CONCLUSION: SMS-based questionnaires on Patient Reported Outcome Measures are a feasible and cost-effective way of prospectively collecting frequent data with acceptable response rates, even shortly after cesarean section. Secondarily 66% of patients reported severe pain during the first 24 h following cesarean section, with the highest pain scores within the initial 12 h. Future studies should focus on optimizing pain-management within this timeframe.

Effect of Context Specificity on Response to the Shortened WOMAC Function Scale in Patients Undergoing Total Knee Arthroplasty.

OBJECTIVE: To determine, in patients undergoing total knee arthroplasty (TKA), whether increasing context specificity of selected items of the shortened version of the Western Ontario and McMaster Universities Osteoarthritis Index function (WOMAC-F) scale (ShortMAC-F) (1) enhanced the convergent validity of the ShortMAC-F with performance-based mobility measures (ii) affected mean scale score, structural validity, reliability, and interpretability. DESIGN: Secondary analysis of randomized clinical trial data. SETTING: A tertiary teaching hospital. PARTICIPANTS: Patients undergoing TKA (N=114). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The ShortMAC-F was modified by specifying the "ascending stairs" and "rising from sitting" items to enquire about difficulty in performing the tasks without reliance on compensatory strategies, whereas the modified "level walking" item enquired about difficulty in walking 400 m. Before and 12 weeks after TKA, patients completed the WOMAC-F questionnaire, modified ShortMAC-F questionnaire, knee pain scale questionnaire, sit-to-stand test, fast gait speed test, and stair climb test. Interpretability was evaluated by calculating anchor-based substantial clinical benefit estimates. RESULTS: The modified ShortMAC-F correlated significantly more strongly than ShortMAC-F or WOMAC-F with pooled performance measures (differences in correlation values, 0.12-0.14). Increasing item context specificity of the ShortMAC-F did not influence its psychometric properties of unidimensionality (comparative fit and Tucker-Lewis indices, >0.95; root mean square error of approximation, 0.05-0.08), reliability (Cronbach's α, 0.75-0.83), correlation with pain intensity (correlation values, 0.48-0.52), and substantial clinical benefit estimates (16 percentage points); however, it resulted in lower mean score (4.5-4.8 points lower). CONCLUSIONS: The modified ShortMAC-F showed sufficient measurement properties for clinical application, and it seemed more adept than WOMAC-F at correlating with performance-based measures in TKA.

Measurement properties of the Foot Function Index (FFI) questionnaire: A systematic review.

OBJECTIVE: Large numbers of people are subject to alterations and pathologies in the foot. To quantify how these problems of foot function affect the quality of life, clinicians and researchers have developed measures such as the Foot Function Index (FFI). Our aim is to determine the methodological quality of the FFI including adaptations to other languages. DATA SOURCES: The studies considered in this review were extracted from the PubMed, Embase and CINAHL databases. The inclusion criteria were followed: (1) studies of patients with no previous foot or ankle pathology and aged over 18 years; (2) based on English-language patient-reported outcome measures that assess foot function; (3) the patient-reported outcome measures should present measurement properties based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria. REVIEW METHODS: The systematic review was conducted following the COSMIN criteria to establish the methodological quality of the original FFI, together with its variants and adaptations. The last search was carried out in May 2024. RESULTS: Of the 1994 studies obtained in the preliminary search, 20 were eligible for inclusion in the final analysis. These results are the validations and cross-cultural adaptations to the following languages: the original FFI has cross-cultural adaptation in 13 languages and the FFI-Revised Short Form has been adapted and validated for use in 2 languages. CONCLUSION: In terms of methodological quality, the FFI-Revised Short Form questionnaire is a valuable instrument for evaluating ankle and foot function and could usefully be expanded to be available in more languages.

Phenotypic and Genetic Alterations in Adult-Onset Cone and Cone-Rod Dystrophy.

INTRODUCTION: The objective of this study was to investigate the clinical characteristics and genetic spectrum of adult-onset cone/cone-rod dystrophy (AOCD/AOCRD) in Korean individuals. METHODS: This is a single-center, retrospective cross-sectional study. We analyzed 22 individuals with genetically confirmed cone dystrophy, with symptoms beginning after 30 years of age. All patients underwent comprehensive ophthalmic and electrophysiological examinations. Exome sequencing of 296 genes associated with inherited retinal disease was performed. The clinical features of patients with AOCD/AOCRD and the causative genes and variants detected by exome sequencing were analyzed. RESULTS: The median age at the first visit was 52 years (range, 31-76 years), and the most common initial symptom was reduced visual acuity. In most cases, fundus photography showed a bull's eye pattern with foveal sparing, consistent with perifoveal photoreceptor loss on optical coherence tomography. We identified disease-causing variants in six genes: RP1, CRX, CDHR1, PROM1, CRB1, and GUCY2D. Pathogenic variants in RP1, CRX, and CDHR1 were identified in 77% of the AOCD/AOCRD cases, including p.Cys1399LeufsTer5, p.Arg1933Ter, and p.Ile2061SerfsTer12 in RP1; p.Ter300GlnextTer118 in CRX; and p.Glu201Lys in CDHR1. No characteristic imaging differences were observed for any of the causative genes. Most of the RP1-related AOCD/AOCRD cases showed a decreased amplitude only in the photopic electroretinogram (ERG), whereas CRX-related AOCD/AOCRD cases showed a slightly decreased amplitude in both the scotopic and photopic ERGs. CONCLUSION: In case of visual impairment with bull's eye pattern of RPE atrophy recognized after the middle age, a comprehensive ophthalmic examination and genetic test should be considered, with the possibility of AOCD/AOCRD in East Asians.

Previous cartilage surgery is associated with inferior patient-reported outcomes after knee arthroplasty.

PURPOSE: The hypothesis of the present study assumed that a history of focal cartilage lesions would not affect Knee Injury and Osteoarthritis Outcome scores (KOOSs) following knee arthroplasty compared to a matched national cohort of knee arthroplasty patients. METHODS: Fifty-eight knee arthroplasty patients with previous surgery for focal cartilage lesions (cartilage cohort) were compared to a matched cohort of 116 knee arthroplasty patients from the Norwegian Arthroplasty Register (control group). Age, sex, primary or revision arthroplasty, type of arthroplasty (total, unicondylar or patellofemoral), year of arthroplasty surgery and arthroplasty brand were used as matching criteria. Demographic data and KOOS were obtained through questionnaires. Regression models were employed to adjust for confounding factors. RESULTS: Mean follow-up post knee arthroplasty surgery was 7.6 years (range 1.2-20.3) in the cartilage cohort and 8.1 (range 1.0-20.9) in the control group. The responding patients were at the time of surgery 54.3 versus 59.0 years in the cartilage and control group, respectively. At follow-up the control group demonstrated higher adjusted Knee Injury and Osteoarthritis Outcome subscores than the previous focal cartilage patients with a mean adjusted difference (95% confidence interval in parentheses): Symptoms 8.4 (0.3, 16.4), Pain 11.8 (2.2, 21.4), Activities of daily living (ADL) 9.3 (-1.2, 18.6), Sport and recreation 8.9 (-1.6, 19.4) and Quality of Life (QoL) 10.6 (0.2, 21.1). The control group also demonstrated higher odds of reaching the patient-acceptable symptom state threshold for the Knee Injury and Osteoarthritis Outcome subscores with odds ratio: Symptoms 2.7 (1.2, 6.4), Pain 3.0 (1.3, 7.0), ADL 2.1 (0.9, 4.6) and QoL 2.4 (1.0, 5.5). CONCLUSION: Previous cartilage surgery was associated with inferior patient-reported outcomes after knee arthroplasty. These patients also exhibited significantly lower odds of reaching the patient-acceptable symptom state threshold for the Knee Injury and Osteoarthritis Outcome subscores. LEVEL OF EVIDENCE: Level III.

Minimal important clinical difference values are not uniformly valid in the active duty military population recovering from shoulder surgery.

BACKGROUND: There are multiple methods for calculating the minimal clinically important difference (MCID) threshold, and previous reports highlight heterogeneity and limitations of anchor-based and distribution-based analyses. The Warfighter Readiness Survey assesses the perception of a military population's fitness to deploy and may be used as a functional index in anchor-based MCID calculations. The purpose of the current study in a physically demanding population undergoing shoulder surgery was to compare the yields of 2 different anchor-based methods of calculating MCID for a battery of PROMs, a standard receiver operating characteristic (ROC) curve-based MCIDs and baseline-adjusted ROC curve MCIDs. METHODS: All service members enrolled prospectively in a multicenter database with prior shoulder surgery that completed pre- and postoperative PROMs at a minimum of 12 months were included. The PROM battery included Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Patient Reported Outcome Management Information System (PROMIS) physical function (PF), PROMIS pain interference (PI), and the Warfighter Readiness Survey. Standard anchor-based and baseline-adjusted ROC curve MCIDs were employed to determine if the calculated MCIDs were both statistically and theoretically valid (95% confidence interval [CI] either completely negative or positive). RESULTS: A total of 117 patients (136 operations) were identified, comprising 83% males with a mean age of 35.7 ± 10.4 years and 47% arthroscopic labral repair/capsulorrhaphy. Using the standard, anchor-based ROC curve MCID calculation, the area under the curve (AUC) for SANE, ASES, PROMIS PF, and PROMIS PI were greater than 0.5 (statistically valid). For ASES, PROMIS PF, and PROMIS PI, the calculated MCID 95% CI all crossed 0 (theoretically invalid). Using the baseline-adjusted ROC curve MCID calculation, the MCID estimates for SANE, ASES, and PROMIS PI were both statistically and theoretically valid if the baseline score was less than 70.5, 69, and 65.7. CONCLUSION: When MCIDs were calculated and anchored to the results of standard, anchor-based MCID, a standard ROC curve analysis did not yield statistically or theoretically valid results across a battery of PROMs commonly used to assess outcomes after shoulder surgery in the active duty military population. Conversely, a baseline-adjusted ROC curve method was more effective at discerning changes across a battery of PROMs among the same cohort.

The Effect of Waiting for a Primary Total Hip Arthroplasty on the Overall Hip Function and Quality of Life.

BACKGROUND: The primary aim was to determine whether time spent awaiting primary total hip arthroplasty (THA) affects patient-reported outcome measures (PROMs) using the Oxford Hip score, Harris Hip Score, and visual analogue scale (VAS) pain. The secondary aim was to assess whether patients have worsening HRQoL, while awaiting THA using the European Quality of Life Five Dimension (EQ-5D) index and EQ-5D health VAS. METHODS: This was a single center cross-sectional study of 190 patients awaiting THA. Patients were divided into waiting "more than 6 months" and "less than 6 months." Baseline and current scores were compared. Multivariate regression analyses were performed to identify predictors of PROM change. RESULTS: No significant intergroup differences were observed for change in preoperative Oxford Hip score, Harris Hip Score, and VAS pain from index consultation to time of study. The EQ-5D index and EQ-5D health VAS decreased significantly further in patients waiting more than 6 months (P = .043, P = .004). Time awaiting THA was significantly associated with a decrease in EQ-5D index and EQ-5D health VAS in multivariate regression (P = .013, P < .001). CONCLUSIONS: Waiting more than 6 months is not associated with a decrease in hip-specific PROMs and longer waiting times are not associated with changes in hip-specific PROMs. Waiting time was associated with a decrease in health-related quality of life and patients waiting more than 6 months had significantly higher decreases in EQ-5D scores. This suggests that living longer with hip osteoarthritis leads to a decrease in QoL, not necessarily through perceived osteoarthritis progression. LEVEL OF EVIDENCE: Level III cross-sectional study.