Assessment Of Clinical Outcomes Research Articles

Patient-reported disease burden in the Accelerate Clinical Trials in Charcot-Marie-Tooth Disease Study.

The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden. Two hundred and fifteen participants underwent serial COAs including the CMT-HI, CMT Functional Outcome Measure (CMT-FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES-R). Correlations between the total and subscale scores for the CMT-HI and other COAs were determined. Changes in the CMT-HI scores over 12 months were assessed using paired t-tests. The minimum clinically important difference (MCID) for the CMT-HI and its subscales were calculated by anchoring to a participant global impression of change scale. At baseline, CMT1A participants were 44.5 ± 15 years old (range: 18-75) and 58% were women. The mean CMT-HI was 25.7 ± 18.8 (range: 0-91.9; 100 reflecting maximal disease burden). The CMT-HI correlated with the CMT-FOM (r = .54, p < .0001), CMTNSv2R (r = .48, p < .0001), and CMTES/CMTES-R (r = .52/r = .54, p < .0001). Disease burden was greater in women than in men (CMT-HI 29.1 ± 19.1 vs. 21.2 ± 17.3, p = .001). Over 12 months, there was a nonsignificant mean increase in CMT-HI of 0.40 ± 10.0 (n = 189, p = .89). The MCID for the CMT-HI total score was 3.8 points (95% CI: 1.7-5.9). Patient-reported disease burden in CMT1A as measured by the CMT-HI is associated with measures of neurologic impairment and physical functioning. Women reported a higher disease burden than men. These data will inform the design of clinical trials in CMT1A.

The Development and Content Validation of the Sjögren's Related Quality of Life Instrument (SRQoL).

Several clinical outcome assessment (COA) instruments assess Sjögren's disease (Sjögren's) symptoms, but do not provide comprehensive assessment of the health-related quality of life (HRQoL) impact of Sjögren's. This study aimed to develop a patient-reported outcome (PRO) instrument for the assessment of HRQoL, intended for use in clinical trials and clinical practice in the assessment of treatment benefit. Review of study sponsor proprietary data and qualitative interviews informed the development of a conceptual model, the Sjögren's Related Quality of Life (SRQoL) and patient global impression of severity (PGI-S) and change (PGI-C) items. Combined concept elicitation and cognitive debriefing interviews with patients with Sjögren's explored their HRQoL impact experience and content validity of the SRQoL and PGI items. Twenty participants were interviewed about their Sjögren's experience. Following inductive analysis of interviews, concepts were categorized into eight domains: emotional well-being (e.g., worry and stress; n = 20/20; 100%), sleep (e.g., daytime sleepiness and waking up during the night; n = 20/20; 100%), activities of daily living (e.g., difficulty looking at screens and difficulty driving; n = 20/20; 100%), cognition (e.g., concentration difficulties and word finding difficulties; n = 19/20; 95.0%), physical functioning (e.g., difficulty walking and difficulty exercising; n = 19/20; 95.0%), social and family functioning (e.g., dependent on others and relationship difficulties; n = 17/20; 85.0%), work (n = 15/20; 75.0%), and sexual functioning (n = 12/20; 60.0%). SRQoL and PGI items, instructions, response options, and recall period were well understood and relevant to participants. The SRQoL is a new PRO instrument to assess Sjögren's impact on HRQoL, developed in accordance with regulatory guidance. This study provides considerable insight into the patient experience of Sjögren's and evidence to support the content validity of the SRQoL. Future research should evaluate the psychometric properties of the SRQoL to support its use in clinical trials and clinical practice and further validate its use as an assessment of treatment benefit.

Conceptualizing meaningful between-group difference in change over time: a demonstration of possible viewpoints.

Determining if group-level differences in health outcomes are meaningful has recently been neglected in favour of determining if individuals have experienced a meaningful change. We explore interpretation of a meaningful between-group difference (MBGD) in clinical outcome assessment scores, primarily in the context of randomized clinical trials. We constructed a series of possible 'viewpoints' on how to conceptualize MBGD thresholds. Each viewpoint is discussed critically in terms of potential advantages and disadvantages, with simulated data to facilitate their consideration. Five viewpoints are presented and discussed. The first considers whether thresholds for meaningful within-individual change over time can be equally applied at the group-level, which is shown to be untenable. Viewpoints 2-4 consider what would have to be observed in treatment groups to conclude a meaningful between-group difference has occurred, framed in terms of the proportion of patients perceiving that they had meaningfully improved. The final viewpoint considers an alternative framework where stakeholders are directly questioned on the meaningfulness of varying magnitudes of between-group differences. The choice of a single threshold versus general interpretative guidelines is discussed. There does not appear to be a single method with clear face validity for determining MBGD thresholds. Additionally, the notion that such thresholds can be purely data-driven is challenged, where a degree of subjective stakeholder judgement is likely required. Areas for future research are proposed, to move towards robust method development.

Determination of Health Concepts in β-Propeller Protein-Associated Neurodegeneration.

β-Propeller protein-associated neurodegeneration (BPAN) is a rare, X-linked condition caused by pathogenic variants in the WDR45 gene that result in a defect of autophagy. Classified as a disorder of neurodegeneration with brain iron accumulation, β-propeller protein-associated neurodegeneration is associated with severe neurologic impairments. With the anticipation of future therapeutic trials, this project characterizes the family's perspective of the impact of disease and defines Health Concepts (HC).Children with a molecularly confirmed diagnosis of β-propeller protein-associated neurodegeneration were enrolled in a prospective natural history study. We administered the Vineland Adaptive Behavior Scales-Third Edition and provided health-related quality of life questionnaires to 42 caregivers. Questionnaires included Pediatric Quality of Life Inventory-Generic Core and Pediatric Quality of Life Inventory-Family Impact modules, Caregiver Priorities and Child Health Index of Life with Disabilities, and Caregiver TBI-CareQoL.The Vineland Adaptive Behavior Scales-Third Edition (n = 42) captured the family's perspective that communication was more affected compared with socialization, activities of daily living (ADL), and motor skills (P < .0001, P < .0001, P = .0053, respectively). Similarly, on the Caregiver Priorities and Child Health Index of Life with Disabilities (n = 26), Pediatric Quality of Life Inventory-Generic Core (n = 27), CareQol (n = 26), and Pediatric Quality of Life Inventory-Family Impact (n = 27), communication abilities, as well as social functioning and activities of daily living, were noted to be most impacted.Through the use of standardized surveys and outcome assessments, we establish the effects of β-propeller protein-associated neurodegeneration on caregiver quality of life. Key health concepts identified by families included overall health, comfort, and communication. The identified HC will inform the future identification of concept of interest and selection of appropriate clinical outcome assessments through the administration of patient-reported outcomes.

Intra-rater agreement of lesion counts in hidradenitis suppurativa.

The heterogeneous presentation of hidradenitis suppurativa (HS) lesions can result in variation in clinical trial outcome assessments when performed by the same rater as well as different raters. In the PIONEER I and II trials of HS patients, there was substantial disagreement between repeated lesion counts by the same rater during a time period in which little true change is expected. Standardization of lesion classification and improved rater training are critical for advancing HS drug development.

7933 Baseline Demographics and Design of the SkybriGHt Registry Study. A US Multi-center, Prospective, Non-interventional, Long-term, Effectiveness and Safety Study of Children and Adolescents with Growth Hormone Deficiency Treated with Lonapegsomatropin

Abstract Disclosure: P.F. Backeljauw: Advisory Board Member; Self; Ascendis Pharma, Inc., Novo Nordisk, BioMarin. Consulting Fee; Self; Ascendis Pharma, Inc., Novo Nordisk, BioMarin, Cavalry, Upsher-Smith. Speaker; Self; Ascendis Pharma, Inc., BioMarin. A.K. Maniatis: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMarin, Novo Nordisk, Pfizer, Inc.. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., OPKO, Novo Nordisk, Pfizer, Inc.. Speaker; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMarin, Novo Nordisk, Pfizer, Inc.. Other; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMarin, Novo Nordisk, Pfizer, Inc. M. Abuzzahab: Advisory Board Member; Self; Ascendis Pharma, Inc., Pfizer, Inc.. Consulting Fee; Self; Rhythm. Research Investigator; Self; Ascendis Pharma, Inc., Novo Nordisk, Lumos, Rhythm, Soleno, Medtronic, Inhale. Other; Self; DSMB for LG. S.D. Chernausek: Advisory Board Member; Self; Ascendis Pharma, Inc. T. Lipman: Speaker; Self; Novo Nordisk. A.K. Dewan: Advisory Board Member; Self; Pfizer, Novo Nordisk. Consulting Fee; Self; Novo Nordisk. Research Investigator; Self; Medtronic. Speaker; Self; Ascendis Pharma, Inc., Novo Nordisk. Other; Self; Twistle. G. Prakasam: Advisory Board Member; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &amp;Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Consulting Fee; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &amp;Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Grant Recipient; Self; Mannkind Corporation. Research Investigator; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &amp;Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Speaker; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &amp;Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Other; Self; Ultragenyx, Pfizer, Inc., Mannkind Corporation, Medtronic, Lilly USA, LLC, Johnson &amp;Johnson, AstraZeneca, Novo Nordisk, Ascendis Pharma, Inc. M.B. Kabbani: Employee; Self; The Pediatric Endocrine &amp; Diabetes Clinic, PC. E. Huang: Employee; Self; Ascendis Pharma, Inc. S. Raveendran: Employee; Self; Ascendis Pharma, Inc. C. Zhao: Employee; Self; Ascendis Pharma, Inc. J.N. Caminis: Employee; Self; Ascendis Pharma, Inc. A.D. Rogol: Advisory Board Member; Self; Ascendis Pharma, Inc., Tolmar. Consulting Fee; Self; Ascendis Pharma, Inc., Tolmar. Other; Self; United States Anti-doping Agency, World Anti-doping agency, Tomlar, Ascendis Pharma, Inc., Up To Date. Objectives: Lonapegsomatropin is a prodrug that delivers unmodified somatropin and is approved by the FDA and EC as a once-weekly treatment for pediatric growth hormone deficiency (pGHD). The overall objectives of the observational SkybriGHt study are to assess safety and effectiveness of lonapegsomatropin in the post-marketing setting. The primary objectives are to describe demographics, clinical characteristics, and treatment patterns. Secondary objectives are to describe clinical outcomes assessments (COAs), long-term outcomes of treatment, treatment adherence and persistence, and outcomes in patients transitioning from childhood to adulthood. Exploratory objectives will examine the impact of adherence on clinical outcomes, and assess all cause and GHD-related resource utilization and costs. A preliminary description of the baseline characteristics and demographics of the first 50 patients enrolled is described here. Methods: In the ongoing SkybriGHt study approximately 900 participants from the US, diagnosed with pGHD and prescribed lonapegsomatropin consistent with routine clinical practice, will be invited to enroll by their HCP. The decision to treat with lonapegsomatropin is made prior to and independently of any potential participation in the study. Participants are enrolled over a 5 year period with the study intended to conclude after 10 years. COAs are collected using questionnaires assessing health-related quality of life in functioning and well-being, treatment satisfaction, and patient preference. Safety is assessed via reporting of adverse events and laboratory test results. Results: Of the first 50 patients enrolled, 11 (22%) had participated in previous trials of lonapegsomatropin, 42 (84%) were male, the median age was 9.9 years (range 3.1, 15.0), and median age at diagnosis was 7.2 years. No participants were previously treated with long-acting GH prior to lonapegsomatropin, and 36 (72.0%) were treated previously with daily GH. Conclusions: The SkybriGHt registry will evaluate the long-term safety, effectiveness, and treatment use patterns (including demographics), with lonapegsomatropin in clinical practice. This preliminary baseline data show that patients were predominantly male, consistent with prior treatment patterns of GHD in the United States. Description of baseline characteristics of additional enrolled patients will be presented. Presentation: 6/3/2024

Sympathetic ophthalmia: epidemiology and cohort-based assessment of clinical outcomes

BackgroundThe purpose of this study was to report the incidence, time after inciting event, aetiology and risk after specific intraocular procedures and the visual outcomes associated with sympathetic ophthalmia (SO)...

Clinical and radiographic results of internal fixation of quadrilateral plate fractures of acetabulum.

Quadrilateral plate (QLP) is a relatively thin bony structure located below the pelvic brim proximal to the hip joint, so management of its fractures is challenging. Evaluation of the functional and radiological outcomes of internal fixation of quadrilateral plate acetabular fractures; comparison of two methods of fracture fixation. A prospective multicentric study including 30 patients who underwent open reduction and internal fixation of QLP fractures through modified Stoppa approach. Patients were divided into two groups according to the method of fixation (anatomical QLP plate vs suprapectineal and infrapectineal plates). Post-operative quality of reduction was evaluated using Matta score. Radiographical assessment according Matta's grading criteria and clinical outcome assessment using the Harris Hip Score (HHS) were repeated at follow-up and at one year to assess displacement. Mean age of patients was 34.9 ± 12.1years. After one year follow-up, clinically mean HHS was 88. ± 5.74. Radiologically post-operative reduction quality was anatomical in 21 (70%) patients, satisfactory in eight (26.7%) patients and unsatisfactory in one (3.3%) patient. Matta's grading at the last follow-up was excellent in 21 (70%) patients, good in six (20%), fair in two (6.7%) patients and poor in one (3.3%) patient. No significant difference was recorded between the two groups in terms of radiographical and clinical results and rate of complications. Accurate reduction of quadrilateral plate fracture with secure fixation through modified Stoppa approach provides good and reproducible outcomes with few complications regardless the type of the implant.

357P Correlation between height, weight, and body mass index z-scores and clinical outcome assessments in young boys with Duchenne muscular dystrophy

357P Correlation between height, weight, and body mass index z-scores and clinical outcome assessments in young boys with Duchenne muscular dystrophy

TCT-346 Assessment of Long-Term Clinical Outcomes of De Novo DCB Performance: A Comprehensive, Individual Patient Data Meta-Analysis of Randomized Clinical Trials: Final Results of the ANDROMEDA Study

TCT-346 Assessment of Long-Term Clinical Outcomes of De Novo DCB Performance: A Comprehensive, Individual Patient Data Meta-Analysis of Randomized Clinical Trials: Final Results of the ANDROMEDA Study

Assessment of Clinical and Functional Outcomes of the Proximal Humerus Internal Locking Compression Plate in Different Neer’s Types of Proximal Humeral Fracture: A Prospective Observational Study

Abstract Background: Over the years, various fixation methods have been developed for managing unstable proximal humerus fractures (PHFs), including conservative and surgical approaches like tension band wiring, suture fixation, intramedullary nailing, hemiarthroplasty, fixed-angled locking plates, and proximal humerus internal locking system (PHILOS) plating. Each method claims superior effectiveness as a fixation device. Aims: The study evaluated the functional outcome of the PHILOS in different parts of the PHF using the Constant–Murley score (CMS), which measures post-operative pain, daily activity ability, limb range of motion (ROM), and strength. Materials and Methods: A prospective observational study of 50 participants aged 16 years and above at Rajasthan Hospitals in Ahmedabad, conducted from July 2020 to July 2022, examined the use of the PHILOS for PHF treatment. Results: The results revealed that two-part fractures had a significantly higher mean CMS (72.4 ± 10.8) compared with three-part (60.8 ± 8.1) and four-part (59.3 ± 5.3) fractures. The P value of 0.0003 indicated that the difference in CMS score between two and three or four parts of PHF after fixing them with PHILOS was statistically significant. Conclusion: The study concludes that using a locking plate for PHFs consistently leads to positive clinical and functional outcomes, including improved CMS, daily living activities, and ROM.

Longitudinal Assessment of Clinical Outcomes for Transitional Care Units

Longitudinal Assessment of Clinical Outcomes for Transitional Care Units

Qualitative Findings for Preparing a Clinical Outcomes Assessment Set (COA) for Nephrotic Syndrome (Prepare-NS)

Qualitative Findings for Preparing a Clinical Outcomes Assessment Set (COA) for Nephrotic Syndrome (Prepare-NS)

The Effect of Resistance Training on Markers of Cachexia in Patients with Heart Failure: A Systematic Review and Meta‐Analysis

ABSTRACTBackgroundCachexia is a metabolic syndrome characterised by muscle wasting that is highly prevalent in subjects with heart failure (HF) and negatively affects physical function, quality of life, morbidity and mortality. Resistance training has been recently incorporated into cardiac rehabilitation exercise programmes to increase muscle strength in patients with HF. This systematic review and meta‐analysis aim to assess the effects of resistance training on markers of cachexia in patients with HF.MethodsFour electronic databases (MEDLINE, Embase, CENTRAL and CINAHL) were searched to identify randomised controlled trials (RCTs) evaluating the effects of resistance training‐only programmes on published criteria for cachexia assessment including muscle strength, body composition (e.g. lean mass/muscle mass) or biochemical markers of cachexia (e.g. inflammatory markers) in patients with HF. Studies were selected based on pre‐specified inclusion and exclusion criteria, with a risk of bias assessment carried out. Meta‐analyses of muscle strength outcomes were completed using RevMan 5.4.1.ResultsNine studies were included in this review. Pooled analysis of one repetition‐maximum strength test of the lower [SMD 0.67 (95% Cl – 0.12, 1.22) p‐value = 0.02] and upper extremities [SMD 1.20 (95% Cl – 0.62, 1.79) p‐value &lt;0.0001] showed a significant increase in muscle strength associated with resistance training, which are both important indicators of physical function. Resistance training did not increase muscle strength during rapid movements measured via peak torque at 60, 90 or 180°/s. There were no significant results recorded for changes in body composition and biochemical markers of cachexia. There were inconsistent findings for the effect of resistance training on quality of life. No studies reported findings on measures of anorexia or fatigue.ConclusionsThe findings of this review reveal the potential benefits of resistance training in preserving and enhancing muscle strength in patients with HF who are at risk of cardiac cachexia. Despite inconclusive results on body composition and quality of life, the inclusion of resistance training in cardiac rehabilitation guidelines has the potential to address issues of muscle weakness and frailty. Specific resistance training protocol recommendations to prevent or treat the development of cachexia cannot be made without the publication of more robust RCTs, specifically examining cachectic patients with heart failure with careful assessment of clinical outcomes of markers of cachexia.

Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) encompass a wide spectrum of rare conditions characterized by diverse phenotypes associated with hundreds of genetic variations, often leading to progressive visual impairment and profound vision loss. Multiple natural history studies and clinical trials exploring gene therapy for various IRDs are ongoing. Outcomes for ophthalmic trials measure visual changes in three main categories-structural, functional, and patient-focused outcomes. Since IRDs may range from congenital with poor central vision from birth to affecting the peripheral retina initially and progressing insidiously with visual acuity affected late in the disease course, typical outcome measures such as central visual acuity and ocular coherence tomography (OCT) imaging of the macula may not provide adequate representation of therapeutic outcomes including alterations in disease course. Thus, alternative unique outcome measures are necessary to assess loss of peripheral vision, color vision, night vision, and contrast sensitivity in IRDs. These differences have complicated the assessment of clinical outcomes for IRD therapies, and the clinical trials for IRDs have had to design novel specialized endpoints to demonstrate treatment efficacy. As genetic engineering and gene therapy techniques continue to advance with growing investment from industry and accelerated approval tracks for orphan conditions, the clinical trials must continue to improve their assessments to demonstrate safety and efficacy of new gene therapies that aim to come to market. Here, we will provide an overview of the current gene therapy approaches, review various endpoints for measuring visual function, highlight those that are utilized in recent gene therapy trials, and provide an overview of stage 2 and 3 IRD trials through the second quarter of 2024.

Building consensus on clinical outcome assessments for BCI devices. A summary of the 10th BCI society meeting 2023 workshop.

The 10th International Brain Computer Interface (BCI) Society Meeting, 'Balancing Innovation and Translation', was held from the 6th to 9th of June 2023 in Brussels, Belgium. This report provides a summary of the workshop 'Building Consensus on Clinical Outcome Assessments (COAs) for BCI Devices'. This workshop was intended to give participants an overview of the current state of BCI, future opportunities, and how different countries and regions provide regulatory oversight to support the BCI community to develop safe and effective devices for patients. Five presentations and a panel discussion including representatives from regulators, industry, and clinical research stakeholders focused on how various stakeholders and the BCI community might best work together to ensure studies provide data that is useful for evaluating safety and effectiveness, including reaching consensus on clinical outcome assessments (COAs) that represent clinically meaningful benefits and support regulatory and payor requirements. This report focuses on the regulatory and reimbursement requirements for medical devices and how to best measure safety and effectiveness and summarizes the presentations from five experts and the discussion between the panel and the audience. Consensus was reached on the following items specifically related to BCI: (i) the importance of and need for a new generation of COAs, (ii) the challenges facing the development of appropriate clinical outcome assessments, and (iii) that improvements in COAs should demonstrate obvious and clinically meaningful benefit(s). There was discussion on: (i) clinical trial design for BCIs and (ii) considerations for payor reimbursement and other funding. Whilst the importance of building community consensus on COAs was apparent, further collaboration will be required to reach consensus on which specific current and/or novel COAs could be used for the BCI field to evolve from research to market.

Assessment of Clinical Outcomes in Patients with Oral Lichen Planus and Oral Lichenoid Lesions (OLP &amp; OLL) Following Treatment with Topical Corticosteroids

Objective: To assess the clinical outcomes in patients with oral lichen planus and oral lichenoid lesions (OLP &amp; OLL) following treatment with topical corticosteroids. Methodology: A total of 175 patients diagnosed with OLP and OLL were recruited from the outpatient department. This cross-sectional study was conducted at Institute of Dentistry (IOD) &amp; CMH, Lahore from July 2023 to December 2023. Inclusion criteria included patients aged 18 years and above with clinically and histopathologically confirmed OLP or OLL lesions. All enrolled patients received topical corticosteroid therapy according to a standardized protocol. Patients were instructed on proper application techniques and advised to adhere to the prescribed treatment regimen. Clinical evaluation of the oral mucosal lesions was performed at baseline and at regular follow-up. Outcome measures included changes in lesion size, severity of symptoms (pain, burning sensation), and overall improvement in clinical appearance. Results: The mean age of the patients was 52.4 years (SD: 10.3). In terms of gender distribution, among the included patients 25 patients (28.57%) were male and 25 patients (71.42%) were female. Among the symptoms observed, Pain was reported by 95 patients (54.28%), Burning Sensation by 110 patients (62.85%), Discomfort by 75 patients (42.85%), and Other symptoms by 20 patients (11.42%). In the clinical outcomes observed with topical corticosteroids, reduction in lesion size was noted in 140 patients, accounting for 80.0%, complete resolution of lesions occurred in 60 patients, representing 34.3%, and reduction in symptoms was reported by 155 patients, constituting 88.6%. Oral candidiasis was noted in 7 patients (4.0%), Mucosal atrophy occurred in 13 patients (7.42%), whereas the majority. Conclusion: In conclusion, our study underscores the efficacy of topical corticosteroid therapy in managing oral lichen planus (OLP) and oral lichenoid lesions (OLL). With 80.0% of patients experiencing a reduction in lesion size, 34.3% achieving complete resolution of lesions, and 88.6% reporting a reduction in symptoms, our findings highlight the significant therapeutic benefits of topical corticosteroids.

Cutaneous Manifestations in Patients with Dermatomyositis, Are They Only Skin Deep?

Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments. The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures. Adult (≥ 18 years) patients (N = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients' experiences of DM, including the symptoms and impacts on their daily lives and wellbeing. Patients reported 13 different skin manifestations of DM. The most common were rash (n = 28, 100%), itch (n = 28, 100%), dry skin (n = 23, 82%), and swelling of the skin (n = 17, 61%). The head and face, followed by hands, were perceived as the most bothersome body areas affected by skin manifestations, because they are exposed and visible to themselves and other people. All patients (n = 28, 100%) reported at least one impact of DM, which varied greatly between patients, but included emotional, psychological, cognitive, and physical impacts, and those affecting daily life, such as work and sleep. Over half of the patients (n = 19, 67%) reported that their daily activities were impacted by DM. The qualitative interviews with patients revealed that the presentation of DM manifestations is highly variable but affects patients' emotional wellbeing, physical activities, and daily life significantly.

Characterization of cryptic complex chromosome rearrangements in balanced chromosomal rearrangement carriers and their PGT-SR clinical outcome assessments

Several reports have presented that balanced chromosomal rearrangements (BCRs) carriers with normal phenotypes may be carriers of complex rearrangements. However, the incidence and PGT clinical outcomes of cryptic complex chromosome rearrangements (CCCRs) in individuals with BCRs is remain unknown. We recruited a cohort of 1,264 individuals with BCR carriers from 2016 to 2021 at the Reproductive and Genetic Hospital of CITIC Xiangya. Peripheral blood was collected for karyotyping and genomic DNA extraction and the PGT-SR clinical outcomes of CCCRs carriers were analyzed and compared with those of BCR carriers. Our findings revealed that 3.6% (45/1,264) of BCR carriers had CCCRs, involving 3–25 breakpoints on 1–3 chromosomes. Furthermore, when mate-pair sequencing was employed, 63.3% (19/30) of CCCR carriers were found to have chromosome rearrangements that were different from those identified by the MicroSeq technique. And the transferable embryo rate of CCCR carriers with 3 chromosomes was significantly lower than that of CCCR carriers with only 1–2 chromosomes. In this research, we revealed that some of the BCR carriers were actually CCCR carriers, and the prognosis of PGT in CCCR carriers with one or two chromosomes is better than that of CCCR carriers with three chromosomes.

Symptoms across the phases of the migraine cycle from the patient's perspective: Results of the MiCOAS qualitative study.

To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.