Assessment Of Clinical Outcomes Research Articles

Clinician/Patient-Reported Outcomes and Their Association Following Root Canal Treatment

IntroductionThe relationship between clinician-reported outcome measures and patient-reported outcome measures after root canal treatment is poorly understood. Oral health–related quality of life (OHRQOL) is a crucial patient-reported outcome measure. Determination of the minimal important difference (MID) is critical for determining patients’ perspective of treatment effectiveness, but the MID required to perceive any meaningful change in the OHRQOL after root canal treatment remains unclear. The aim of this prospective study was to investigate the relationship between the clinical outcome and OHRQOL after root canal treatment and to determine the corresponding MID values. MethodsPatients (N = 64) requiring primary nonsurgical root canal treatment were recruited. Clinical and radiographic (cone-beam computed tomography) assessment of treatment outcomes was performed at the 12-month follow-up. OHRQOL and pain were evaluated preoperatively and at the 12-month follow-up using the Oral Health Impact Profile-14 and visual analog scale, respectively. P < .05 was considered statistically significant. MID was assessed using distribution- and anchor-based approaches. ResultsThe final analysis included 47 patients. The clinical outcome was favorable for 92.6% of teeth. OHRQOL and pain showed significant improvement after treatment (P < .001). No significant association was found between clinical outcome and OHRQOL (P > .05). The mean Oral Health Impact Profile-14 score change (ie, 13.6) was greater than the range of MID values determined. ConclusionsRoot canal treatment significantly improves OHRQOL. Improvement in the OHRQOL score was greater than the MID values determined, implying a clinically significant change. OHRQOL does not appear to be correlated with clinician-reported outcome measures.

Development of a signs and symptoms outcome measure for caregivers of patients with methylmalonic acidemia and propionic acidemia (MMAPAQ)

Background and objectiveMethylmalonic acidemia (MMA) and propionic acidemia (PA) are rare inborn errors of metabolism with shared signs and symptoms that are associated with significant morbidity and mortality. No disease-specific clinical outcomes assessment instruments for MMA and/or PA currently exist to capture the patient perspective in clinical trials. Because patients with these conditions are generally young and have cognitive impairments, an observer-reported outcome (ObsRO) instrument is crucial. We report results from qualitative research supporting development of the Methylmalonic Acidemia and Propionic Acidemia Questionnaire (MMAPAQ), a signs and symptoms ObsRO measure for caregivers of patients with MMA and/or PA. MethodsConcept elicitation (CE) interviews were conducted with 35 participants across 2 studies who were aged ≥18 years and caregivers of patients with a confirmed diagnosis of MMA or PA, and an additional 5 patients aged ≥6 years with MMA or PA in Study 1, to identify core signs/symptoms for inclusion in the MMAPAQ. All interviews were conducted in English. Study 2 included cognitive interviews (CI) with caregivers and clinical experts to further assess content validity. CE and a conceptual framework review were also conducted with clinical experts to further support findings. ResultsA consistent set of signs/symptoms of MMA and PA were reported by eligible caregivers interviewed in study 1 (n = 21) and study 2 (n = 14), representing 11 patients with MMA and 20 with PA. Based on concepts reported in study 1, a draft instrument was constructed and compared with the Pediatric Quality of Life Inventory™ (PedsQL™) and Family Impact module, demonstrating face validity for measuring key signs/symptoms important to patients and caregivers. The PedsQL™ and Family Impact modules were preferred to assess patient and caregiver impacts. Two waves of CE and CIs were conducted in study 2, with wave 1 resulting in removal of 7 items and other revisions to improve clarity, and wave 2 resulting in modification of examples used for 2 items. The final instrument consisted of the following 7 items assessed over the past 7 days using a Likert-type response scale ranging from “never” to “very often”: uncontrollable or involuntary movements, dehydration, rapid breathing at rest, appearing lethargic, appearing disinterested in eating, refusing to eat, and vomiting. ConclusionsThis study establishes the content validity of the MMAPAQ as the first ObsRO questionnaire for measuring core signs and symptoms of MMA and PA in clinical trials and community research. Scoring and psychometric measurement properties of the MMAPAQ will be established in future studies. The PedsQL™ was found to have face validity in measuring concepts that affect the MMA and PA patient populations and should also be considered for use in clinical trials in MMA and PA.

A framework for best practices in clinical outcome assessment (COA) concept mapping: a case study.

Mapping or matching the items in a clinical outcome assessment (COA) to concepts that define a condition is a common method for evaluating a COA's concept coverage. The purpose of this research was to address the lack of formal guidance for conducting this task by developing a framework for best practices in COA concept mapping and applying it to a case study. To develop the framework, we examined the literature and created a draft set of best practices which was then reviewed by experienced researchers through focus groups before being finalized. To conduct the case study, we extracted data from a systematic review of knee osteoarthritis (KO) symptoms and impacts and used the framework to map relevant concepts to items in the SF-36v2® Health Survey (SF-36v2). The framework guides researchers in defining the purpose of and data sources for the mapping, establishing guiding principles and decision-making thresholds, and conducting the mapping exercise. The results of the case study demonstrate the usefulness of the framework in identifying 27/36 items (75%) in the SF-36v2 that addressed concepts that define KO. This case study illustrates how the framework for best practices in COA concept mapping may be used, highlighting how establishing clear concept definitions and guiding principles and following a structured process throughout can help produce consistent, reliable, and reproducible results. The results from this rigorous approach can provide valuable evidence to support decisions about the appropriateness of a COA for the intended patient population.

Quantitative Comparisons of Progressive Supranuclear Palsy Rating Scale Versions Using Item Response Theory.

Progressive supranuclear palsy (PSP) is a neurodegenerative, late-onset disease that is challenging in terms of assessment. The Progressive Supranuclear Palsy Rating Scale (PSPRS), a 28-item clinician-reported scale, is the most established clinical outcome assessment method. Recently, the U.S. Food and Drug Administration (FDA) has proposed a subscale of 10 items as an alternative to full PSPRS. To quantitatively evaluate and compare the properties of full PSPRS and the FDA subscale using item response theory. To develop a progression model of the disease and assess relative merits of study designs and analysis options. Data of 979 patients from four interventional trials and two registries were available for analysis. Our investigation was divided into: (1) estimating informativeness of the 28 items; (2) estimating disease progression; and (3) comparing the scales, trial designs, and analysis options with respect to power to detect a clinically relevant treatment effect. PSPRS item scores had a low pairwise correlation (r = 0.17 ± 0.14) and the items irritability, sleep difficulty, and postural tremor were uncorrelated with the other items. The FDA-selected items displayed higher correlation (r = 0.35 ± 0.14) and were the basis for a longitudinal item response model including disease progression. Trial simulations indicated that identification of a disease-modifying treatment effect required less than half the study size if the analysis was based on longitudinal item information compared with total scores at end-of-treatment. A longitudinal item response model based on the FDA-selected PSPRS items is a promising tool in evaluating treatments for PSP. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

114. Assessment of clinical outcomes and pain management of single-level lumbar laminectomy between unilateral biportal endoscopic, tubular, and open approaches

114. Assessment of clinical outcomes and pain management of single-level lumbar laminectomy between unilateral biportal endoscopic, tubular, and open approaches

An interdisciplinary integrated specialized one-stop outpatient clinic for idiopathic intracranial hypertension-a comprehensive assessment of clinical outcome.

Management of idiopathic intracranial hypertension (IIH) is complex requiring multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges for healthcare professionals and patients. Thus, an interdisciplinary integrated outpatient clinic for IIH (comprising neurology, neuroophthalmology, neuroradiology, neurosurgery and endocrinology) was established with central coordination and a one-stop concept. Here, the aim was to evaluate the effects of this one-stop concept on objective clinical outcome. In a retrospective cohort study, the one-stop era with integrated care (IC) (1 July 2021 to 31 December 2022) was compared to a reference group receiving standard care (SC) (1 July 2018 to 31 December 2019) regarding visual impairment/worsening and headache improvement/freedom 6 months after diagnosis. Multivariate binary logistic regression models were used to adjust for confounders. Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female 90.6% vs. 90.1%; mean age 33.6 vs. 32.8 years; median body mass index 31.8 vs. 33.0; median cerebrospinal fluid opening pressure 32 vs. 34 cmH2O; at diagnosis, visual impairment was present in 71.8% vs. 69.1% and chronic headache in 55.3% vs. 56.8% in IC vs. SC). IC was associated with a higher likelihood of achieving both headache improvement (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.52-4.33, p < 0.001) and headache freedom (OR 1.75, 95% CI 1.11-3.09, p = 0.031). Regarding the risk of visual impairment and visual worsening IC was superior numerically but not statistically significantly (OR 0.87, 95% CI 0.69-1.16, p = 0.231, and OR 0.67, 95% CI 0.41-1.25, p = 0.354). Interdisciplinary integrated care of IIH is favourably associated with headache outcomes and potentially also visual outcomes.

Regulatory Pathways for Qualification andAcceptance of Digital Health Technology-Derived Clinical Trial Endpoints: Considerations for Sponsors.

Despite widespread interest and substantial investment in the adoption of sensor-based digital health technologies (sDHTs) for remote data capture in drug development trials, no drug has been approved based on an sDHT-derived primary endpoint in the United States (US). One reason for this lack of advancement is the complexity of obtaining regulatory endorsement for those endpoints within current US regulatory pathways. The goal of our review is to describe the two choices currently available to pharmaceutical study Sponsors: (i) they may navigate the traditional route of compiling the evidence to support the sDHT-derived endpoint in their investigational new drug (IND) application, requiring specific expertise and substantial resources; or (ii) they may navigate the drug development tool (DDT) pathway with the goal of qualifying their sDHT-derived endpoint as a biomarker or clinical outcome assessment applicable to a broader context of use (COU), either alone or as part of a partnership or consortium. We describe the nuances of each pathway; the evidentiary requirements for supporting an sDHT-derived endpoint and the technology used to capture it; and the impact that an sDHT's regulatory status may have on a Sponsor's decision to use it for data capture. By systematically comparing the IND and DDT pathways, our over-arching goals are to support the increasing deployment of sDHTs within the clinical research setting and help advance regulatory science in the field of digital medicine.

Pozelimab for CHAPLE disease: results from in-trial interviews and clinical outcome assessments

BackgroundCD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634).MethodsInterviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change.ResultsTen patients (aged 3–19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (≥ 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from “mild” to “very severe” at baseline to “no signs or symptoms” at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores.ConclusionsPatients with CHAPLE disease treated with pozelimab for 24 weeks experienced complete resolution of core signs and symptoms. Mixed-methods approaches can contextualize the patient experience (how patients feel and function) in rare disease trials.Trial registrationClinicaltrials.gov, NCT04209634, registered December 24, 2019, https://classic.clinicaltrials.gov/ct2/show/NCT04209634.

Assessment of clinical profile and outcome of upper gastrointestinal bleed in patients with liver cirrhosis: a prospective study in a tertiary care hospital in Northeast India

Assessment of clinical profile and outcome of upper gastrointestinal bleed in patients with liver cirrhosis: a prospective study in a tertiary care hospital in Northeast India

Preparation and Rationale for a Patient-Centered Clinical Outcome Assessment Set of Fluid Overload for Drug Development in Nephrotic Syndrome

Introduction: Fluid overload is a source of substantial morbidity for adults and children with nephrotic syndrome (NS). Preparation and Rationale for a Fluid Overload in Nephrotic Syndrome Clinical Outcomes Assessment Set for Drug Development (Prepare-NS, 5UG3FD007308) was funded by the US Food and Drug Administration to develop a core set of patient-reported and observer-reported (for young children) outcome measures of fluid overload for use in pharmaceutical trials across the lifespan. Methods: The Prepare-NS study team developed the proposed context of use with input from stakeholders. We conducted a scoping review to assess the available literature on relevant patient- and observer-reported measures and performed secondary analyses of existing qualitative and quantitative data. Results: The outcome set will aim to serve individuals 2 years of age and older with primary NS conditions (specifically focal segmental glomerulosclerosis, minimal change disease, IgM nephropathy, membranous nephropathy, and childhood-onset NS not biopsied). The existing literature describing patient-reported outcomes in NS largely relies on nonspecific measures of health-related quality of life; fluid overload has been associated with lower scores on these measures. Conclusion: To address the gap in measure availability and fluid overload content, the Prepare-NS team has launched a set of qualitative studies for concept elicitation from the population of interest to inform development of new measures. The resulting measures subsequently will undergo psychometric evaluation and validation in a survey study.

Effect of preoperative autologous platelet-rich plasmapheresis on postoperative bleeding in patients undergoing heart valve surgery.

Cardiovascular surgeries often require deep hypothermic circulatory arrest and cardiopulmonary bypass (CPB), which can disrupt blood clotting and lead to excessive bleeding. Traditional treatments involve transfusing blood and blood products, which can have adverse effects and place significant strain on the global blood supply. Research suggests that autologous platelet-rich plasmapheresis (aPRP) may reduce the need for transfusions by preserving blood components. However, the impact of aPRP on postoperative blood loss and clinical outcomes in cardiovascular surgery remains controversial. This study aimed to examine the effects of aPRP on postoperative blood loss and recovery in patients undergoing heart valve surgery. A total of 183 patients were divided into either aPRP or control groups. The aPRP group received aPRP before CPB, whereas the control group did not. The primary endpoint was postoperative bleeding between the groups. The secondary endpoints were postoperative bleeding risk factors and clinical outcome assessment. Logistic regression analysis with covariate adjustment was used to calculate these risk factors. A total of 76 patients (41.5%) in the aPRP group and 107 patients (58.5%) in the control group were included in the analysis. No significant difference was found in the occurrence of postoperative bleeding [odds ratio (OR) =0.53, 95% confidence interval (CI): 0.28-1.00, P=0.05], and the aPRP group had fewer complications than the controls (OR =0.28, 95% CI: 0.10-0.68, P=0.009). However, after adjusting for the New York Heart Association (NYHA) classification, diabetes, arrhythmology, mean activated clotting time (ACTmean), CPB, bleeding, thoracotomy, and body mass index (BMI), there was a significant difference in postoperative bleeding (adjusted OR =0.47, 95% CI: 0.22-0.98, P=0.04) and complications (adjusted OR =0.23, 95% CI: 0.07-0.64, P=0.008) between the two groups. Preoperative aPRP can improve postoperative outcomes and reduce complications in patients undergoing heart valve surgery.

Assessment of Direct Oral Anticoagulant Use and Clinical Outcomes among Patients with Renal Impairment at Faculty of Medicine Siriraj Hospital, Mahidol University

Assessment of Direct Oral Anticoagulant Use and Clinical Outcomes among Patients with Renal Impairment at Faculty of Medicine Siriraj Hospital, Mahidol University

La Crosse virus encephalitis in children.

La Crosse virus encephalitis (LACV-E) is among the most common neuroinvasive arthropod-borne viral infections of childhood in North America. Children are uniquely predisposed to symptomatic disease, whereas symptomatic adult infections remain uncommon. Infection results frequently in neurologic symptomatology including headaches, seizures, and altered mentation, often necessitating hospitalization and significant diagnostic evaluation. The purpose of this review is to provide a contemporary assessment of clinical, laboratory, and neurobehavioral outcomes of children with LACV-E. Common clinical manifestations at presentation, specifically seizure activity and altered mental status, are independent predictors of disease severity. Epileptiform discharges on electroencephalogram (EEG) during hospitalization may predict long-term epilepsy diagnosis. Lastly, long-term neurologic sequelae from acute infection is persistent and likely under-recognized among children with LACV-E. As climate change alters the geographic distribution of mosquito borne illnesses, a possibility of regional expansion of La Crosse virus (LACV) endemicity exists. The above data highlight readily identifiable features and testing modalities for clinicians who may encounter this viral infection. Importantly, an emphasis on long term neurobehavioral follow up is necessary to better identify and provide support of affected individuals. Future research in identifying host immune responses to LACV infection, as well as therapeutic options, are needed.

Assessment of Hepatocellular Carcinoma Patients Infected with Covid-19 Infection during the Pandemic

Hepatocellular carcinoma (HCC) patients are more susceptible to decompensation if they get Coronavirus disease 2019 (COVID-19) infection that leads to significant reduction in HCC related health services, reduction in surveillance activities and progression of HCC. On the other hand, symptoms of covid-19 infection are usually severe in HCC patients. Assessment of severity of covid-19 infection in HCC patients. And assessment of clinical course and outcome of HCC patients when they get infected by Covid-19. This is a retrospective case control study including 100 HCC patients (50 of them were infected by covid-19 while the other 50 were not infected). All patients were Egyptians presented to HCC clinic in national hepatology &amp; tropical research institute (NHTMRI) from 1/2022 to 1/2023 assessed for covid-19 infection (by typical CT chest, covid swab and covid symptoms) and assessed for HCC staging (by Barcelona clinic liver cancer BCLC), clinical course over six months (by Child Pugh score) and mortality rates. Most of Covid-19 infected HCC patients had severe covid symptoms and progressive HCC course with mortality 72%, while low percentage of covid-19 HCC infected group were mild with stationary course. On the other hand, high percentage of non-infected HCC group have stationary HCC course with low mortality 24%. COVID-19 infection seems to have a significant effect on clinical course and outcome of HCC. Also, HCC patients are vulnerable to have more severe COVID-19 symptoms.

Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort

BackgroundFunctional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. ObjectiveTo evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. Patients and methodsThe Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016–2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores – both before and after treatment – as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents’ assessments. ResultsThe median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. ConclusionThis is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

Clinical outcome assessment of colistin sulphate in children with carbapenem-resistant organism infections: First data from China

ObjectivesColistin sulphate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese paediatric patients with carbapenem-resistant organism infections. The purpose of this short communication is to provide a brief overview of the findings to date. MethodsWe reviewed the electronic medical records of paediatric patients (aged 9–17 y) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions. ResultsA total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment. ConclusionsIn this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of carbapenem-resistant organism infections in Chinese children.

Development of the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA): A De Novo IGA of Cutaneous Manifestations of Dermatomyositis.

Dermatomyositis (DM) is a rare systemic autoimmune disease characterized by a distinctive debilitating skin rash and skeletal muscle weakness. It is unclear if existing clinical outcome assessment (COA) measures include the concepts of priority to patients and those necessary to fully capture improvements in the active cutaneous manifestations of DM. This study aimed to develop the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA), a de novo IGA, for use in clinical trials of adult DM. Eight DM clinical experts participated in 60-min qualitative interviews consisting of concept elicitation and cognitive debriefing methodologies. Concept elicitation comprised open-ended questions with follow-up probes to explore clinicians' experiences of treating patients with DM, the impact of symptoms on patients' quality of life, and the severity levels of disease characteristics to explore DM progression. Cognitive debriefing required the clinical experts to perform a review of the CDM-IGA, designed to assess the severity of cutaneous disease activity of DM. After the interviews, a consensus meeting with three clinical experts was held to agree on any outstanding issues relating to the CDM-IGA. The CDM-IGA was iteratively developed using the opinions of nine clinical experts. Feedback provided by all clinicians agreed that erythema was the main active cutaneous manifestation of DM and should be the primary characteristic on the CDM-IGA, split by erythema color and extent. To determine cutaneous disease severity, experts suggested adding a metric called secondary changes, which combined erosion/ulceration and lichenification, which could modify the patient's final score. Three clinical experts suggested that a photo-guide to support assessments of erythema across different skin tones could be beneficial. A novel CDM-IGA was developed for use with adult patients with DM in clinical trials, based on an iterative development process that combined qualitative feedback from clinical experts of DM and importantly adult patients living with DM.

A - 44 A Comparison of Multi-Domain Clinical Assessment Outcomes in Older Adults Following Concussion

A - 44 A Comparison of Multi-Domain Clinical Assessment Outcomes in Older Adults Following Concussion

Modification of a parent-report sleep scale for individuals with CDKL5 deficiency disorder: a psychometric study.

Sleep difficulties are common in CDKL5 deficiency disorder (CDD), a developmental and epileptic encephalopathy (DEE). This study evaluated the factor structure of the Disorders of Initiating and Maintaining Sleep (DIMS), Disorders of Excessive Daytime Somnolence (DOES) and Sleep Breathing Disorders (SBD) domains of the Sleep Disturbance Scale for Children (SDSC) for CDD. A cross-sectional psychometric study design was used. Data were collected for 125 individuals aged 3 years or older who attended a US Centers of Excellence clinic or registered with the International CDKL5 Disorder Database. The median age was 10.3 years (range 3.2 - 40.7 years) and 105 (84%) were female. Two of the three SBD items related were not observed by most respondents and analysis was restricted to the DIMS and DOES domains. Using all items in the initial confirmatory factor analysis, two items in the DIMS domain and one item in the DOES domain loaded poorly. After deleting these items and repeating the analysis, item loading (0.524-0.814) and internal consistency (DIMS: 0.78, DOES: 0.76) statistics were good. The square of the inter-domain correlation coefficient was 0.17, less than Average Variance Extracted values for both domains and indicating good discriminant validity. The Tucker-Lewis and Comparative Fit indices were slightly lower than the threshold of >0.9 for establishing goodness of fit. The modified DIMS and DOES domains from the SDSC could be suitable clinical outcome assessments of insomnia and related impairments in CDD and potentially other DEE conditions.

RNA mis-splicing in children with myotonic dystrophy is associated with physical function.

Dysregulated RNA alternative splicing is the hallmark of myotonic dystrophy type 1 (DM1). However, the association between RNA mis-splicing and physical function in children with the most severe form of disease, congenital myotonic dystrophy (CDM), is unknown. 82 participants (42 DM1 adults & 40 CDM children) with muscle biopsies and measures of myotonia, motor function, and strength were combined from five observational studies. Data were normalized and correlated with an aggregate measure of alternative splicing dysregulation, [MBNL] inferred in skeletal muscle biopsies. Multiple linear regression analysis was performed to predict [MBNL] inferred using clinical outcome measures alone. Similar analyses were performed to predict 12-month physical function using baseline metrics. Myotonia (measured via vHOT) was significantly correlated with RNA mis-splicing in our cross-sectional population of all DM1 individuals; CDM participants alone displayed no myotonia despite a similar range of RNA mis-splicing. Measures of motor performance and muscle strength were significantly associated with [MBNL] inferred in our cohort of all DM1 individuals and when assessing CDM children independently. Multiple linear regression analyses yielded two models capable of predicting [MBNL] inferred from select clinical outcome assessments alone in all subjects (adjusted R 2 = 0.6723) or exclusively in CDM children (adjusted R 2 = 0.5875). Our findings establish significant correlations between skeletal muscle performance and a composite measure of alternative splicing dysregulation, [MBNL] inferred, in DM1. The strength of these correlations and the development of the predictive models will assist in designing efficacious clinical trials for individuals with DM1, particularly CDM.