Assessment Of Clinical Outcomes Research Articles

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.

Item performance of the scale for the assessment and rating of ataxia in rare and ultra-rare genetic ataxias.

The Scale for the Assessment and Rating of Ataxia (SARA) is widely used for assessing the severity and progression of genetic cerebellar ataxias. SARA is now considered a primary end point in several ataxia treatment trials, but its underlying composite item measurement model has not yet been tested. This work aimed to evaluate the composite properties of SARA and its items using item response theory (IRT) and to demonstrate its applicability across even ultra-rare genetic ataxias. Leveraging SARA subscores data from 1932 visits from 990 patients of the Autosomal Recessive Cerebellar Ataxias (ARCA) registry, we assessed the performance of SARA using IRT methodology. The item characteristics were evaluated over the ataxia severity range of the entire ataxia population as well as the assessment validity across 115 genetic ARCA subpopulations. A unidimensional IRT model was able to describe SARA item data, indicating that SARA captures one single latent variable. All items had high discrimination values (1.5-2.9) indicating the effectiveness of the SARA in differentiating between subjects with different disease statuses. Each item contributed between 7% and 28% of the total assessment informativeness. There was no evidence for differences between the 115 genetic ARCA subpopulations in SARA applicability. These results show the good discrimination ability of SARA with all of its items adding informational value. The IRT framework provides a thorough description of SARA on the item level, and facilitates its utilization as a clinical outcome assessment in upcoming longitudinal natural history or treatment trials, across a large number of ataxias, including ultra-rare ones.

Abstract PO5-11-12: The use of wearable sensors and patient-reported outcomes in breast cancer research: A literature survey

Abstract Background: Clinical outcome assessments (COAs) related to physical activity, sleep, and functional mobility (gait and balance) are common in breast cancer research as they provide insight into treatment effects and overall quality of life. Wearable sensors offer utility in supplementing traditional COAs by providing objective data by passive, continuous measurement, thereby gaining unique insight on functioning while reducing patient burden. However, a comprehensive understanding of how wearables are being used in breast cancer research and how they correlate with subjective measurement of functioning is lacking. Our aim was to identify how wearable sensors and patient-reported outcomes (PROs) are being utilized in breast cancer research, the common areas of overlap, as well as areas in which expanded use of wearable sensors may be beneficial in clinical breast cancer research. Methods: We conducted a non-systematic survey of breast cancer literature using electronic databases (PubMed, Web of Science, Elsevier and Clinicaltrials.gov) to identify oncology trials using both wearable sensors and PROs. Details such as PROs used, types of sensors used, and the data collected from these were extracted and summarized. There were no restrictions placed on the date and year of publication. Results: A total of 15 breast cancer studies, which used both wearable sensors and PROs to measure patient outcomes, were included in analysis. Accelerometers were implemented most frequently in the studies analyzed (73%) followed by pedometers (40%). The most common outcomes measured using wearable sensors were physical activity (47%) and sleep (47%), with only 1 study (7%) measuring functional mobility(gait and balance). The most common outcomes measured using PROs were sleep (47%), followed by quality of life (40%), physical activity (33%), and “other” parameters (40%; e.g., mood, fatigue, pain). Correlation between PRO and sensor metrics were sparce (20%), yet sensor measures of physical activity, sleep, and gait/balance correlated respectively with PROs of activity, sleep, and quality of life. Conclusions: Sleep, quality of life, and physical activity were the most common outcomes measured by PROs, while physical activity and sleep were the most common outcomes captured using wearable sensors. These results suggest there is alignment in outcomes gathered from wearable sensors and PROs, however additional insight may be gained by incorporating wearable sensors for assessment of functional mobility (e.g. walk or balance tests) as these areas are known to impact quality of life in cancer patients and cancer survivors. Further, few studies analyzed correlations between the two measurement systems, suggesting a greater need in understanding how objective measures via wearable sensors and subjective measurements relate. Citation Format: Kelly Dumais, Adam Jagodinsky, Saima Khakwani, Rebecca Bonaker, Bryan McDowell, Kristen Sowalsky. The use of wearable sensors and patient-reported outcomes in breast cancer research: A literature survey [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-12.

Abstract PO5-12-07: Analyzing Patient Experiences with Adjuvant Hormone Therapy for Early Breast Cancer Treatment via NLP/ML on Social Media: Symptoms and Their Mitigation

Abstract Understanding the early breast cancer (eBC) patient experience of disease and treatment is critical to addressing unmet patient needs, improving outcomes, and informing the next wave of drug development. Traditional approaches, such as interviews or focus group studies, are resource intensive and have limitations in reflecting the diverse experiences of patients with different disease characteristics, treatments, and sociodemographic backgrounds, and in detecting rare severe events that could potentially lead to therapy discontinuation. To overcome these limitations, we have developed a semi-automated approach utilizing Natural Language Processing (NLP) and Machine Learning (ML) methods in application to public patient forums to extract patient insights. Specifically, we analyzed 500,000 anonymized posts from the BreastCancer.org forum, utilizing Transformer-based methods to identify posts related to eBC patient experiences treated with standard hormonal therapies (HT). First, a novel ML-based model identified posts related to eBC adjuvant HT. For those, patient demographics, symptoms and their severity, and symptom management strategies such as exercise and yoga were subject to further analysis. Out of 362,074 relevant eBC posts, 32 symptoms and 9 impacts were significantly associated with at least one of the six hormonal therapies we considered. Hot flushes (relative risk [RR]: 6.70; 95% CI: 3.36–13.36), arthralgia (RR: 6.67; 95% CI: 3.53–12.59), weight increase (RR: 4.83; 95% CI: 3.20–7.28), mood swings (RR: 7.36; 95% CI: 5.75–9.42), insomnia (RR: 4.76; 95% CI: 3.14–7.22), and depression (RR: 3.05; 95% CI: 1.71–5.44) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥1 HT despite their low overall prevalence in eBC posts. Notably, posts contained a wide range of symptoms severity, including rarely seen symptoms in smaller patient pools, such as severe night hot flashes leading to treatment discontinuation. Symptoms/impacts mentioned in association with exercise and yoga as a way for symptom mitigation included hot flashes, arthralgia, fatigue, anxiety, depression, and pain. Of those posts, 53.3% to 82.5% reported positive or neutral sentiments for exercise, and 22.2% to 100.0% for yoga. For posts specifically mentioning the management of side effects of HT, between 50.0% and 63.5% had a positive sentiment associated with exercise concerning each of the symptoms/impacts with a lower positive impact related to yoga (between 11.1% and 43.0% of posts). Posts discussing pain management and exercise included a higher proportion of negative feedback, versus positive sentiment for depression. Posts related to yoga as an HT symptom mitigation strategy had a higher prevalence of negative sentiments for anxiety and depression. Our proposed ML/NLP-based approach to collecting patient feedback from publicly available forums complements standard qualitative methods by enabling the scalable extraction of insights from hundreds of thousands of online conversations that could span a broad diversity of symptoms and well-being reflections. Furthermore, our findings suggest the potential value of informing clinical outcome assessment (COA) measurement for clinical trials, alone and in combination with standard qualitative research approaches to guide the next clinical development. Overall, our study highlights the significant potential of NLP and ML to address the critical need to better understand the eBC patient experience of disease and treatment to improve outcomes for patients. Citation Format: Sameet Sreenivasan, Chao Fang, Emuella Flood, Natasha Markuzon, Jasmine Sze. Analyzing Patient Experiences with Adjuvant Hormone Therapy for Early Breast Cancer Treatment via NLP/ML on Social Media: Symptoms and Their Mitigation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-07.

Business case for psychosocial interventions in clinics: potential for decrease in treatment discontinuation and costs

Research questionFrom a value-based healthcare (VBHC) perspective, does an assessment of clinical outcomes and intervention costs indicate that providing cognitive behavioural therapy (CBT) or mindfulness to women seeking fertility treatment have added value compared with no such intervention? DesignProof-of-concept business case based on a VBHC perspective that considers both clinical outcomes and costs. Potential impacts in psychological and fertility outcomes were based on existing literature. Cost outcomes were estimated with a costing model for the Dutch fertility treatment setting. Results32 studies were identified; 13 could be included. Women who received CBT had 12% lower anxiety, 40% lower depression, and 6% higher fertility quality of life; difference in clinical pregnancy rates was 6-percentage points (CBT=30.2%; Control=24.2%); difference in fertility discontinuation rates was 10-percentage points (CBT=5.5%; Control=15.2%). Women who received training in mindfulness had 8% lower anxiety, 45% lower depression, and 21% higher fertility quality of life; difference in mean clinical pregnancy rate was 19-percentage points (Mindfulness=44.8%; Control=26.0%). Potential total cost savings for the was approximately €1.2 million per year if CBT was provided and €11 million if mindfulness was. Corresponding return-on-investment for CBT was 30.7% and for mindfulness 288%. Potential cost benefits are influenced by the assumed clinical pregnancy rates; such data related to mindfulness was limited to one study. ConclusionsThis proof-of-concept VBHC business case suggests providing CBT or mindfulness to women seeking fertility treatment could have added value. This conclusion would be bolstered by higher quality primary studies on the effect of mindfulness on clinical pregnancy rates.

Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy.

Stride Velocity 95th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. To compare SV95C-in its first-ever clinical trial application as a secondary endpoint-with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). SV95C was a secondary endpoint in a subset (n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6-11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures. SV95C change at Week 24 was -0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong (r = 0.611-0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong (r = 0.443-0.678).∥. Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C's sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials.

Development of an Infantile GM2 Clinical Rating Scale: Remote Assessment of Clinically Meaningful Health-Related Function.

GM2 gangliosidoses (GM2) are a group of rare lysosomal storage disorders in which accumulation of GM2 gangliosides results in progressive central nervous system damage. The infantile GM2 phenotype is characterized by delays in milestones by 6 months of age, followed by rapid loss of motor, cognitive, and visual function. Advancements in early diagnosis and pharmacotherapies provide promise for improved outcomes. However, the lack of feasible and clinically meaningful clinical outcome assessments for GM2 poses a challenge to characterizing GM2 natural history and selecting clinical trial endpoints. The purpose of this study was to develop a remotely administered infantile GM2 rating scale to measure health-related function in children with infantile GM2. A 2-phase mixed methods design was employed. In phase 1 of the study, 8 families of children with Infantile GM2 completed a natural history survey and a 1:1 semistructured interview to provide caregiver perspectives on the impacts of GM2 on health-related function. In phase 2 of the study, 8 expert clinicians provided feedback via surveys and participated in videoconference-hosted focus groups to refine scale administration and scoring procedures. These methods guided the development of 16 scale items to assess function in 5 health-related function domains: vision, hand and arm use, communication, gross motor, and feeding. This study used caregiver perspectives and expert clinician feedback to develop a remotely administered clinical outcome assessment of clinically meaningful health-related function in children with infantile GM2. Future studies will further evaluate the feasibility, reliability, and validity of the Infantile GM2 Clinical Rating Scale.

Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments

BackgroundChronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients’ health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient’s functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited.MethodsThis two-stage qualitative study used semi-structured interviews in patients aged 45–80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30–80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction.ResultsIn Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results.ConclusionThe qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies.Trial numberGSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473.

Assessment of Clinical Outcomes in Patients With Osteoarthritis: Analysis From the UK Medical Cannabis Registry

Osteoarthritis accounts for 0.6% of disability-adjusted life years globally. There is a paucity of research focused on cannabis-based medicinal products (CBMPs) for osteoarthritic chronic pain management. This study aims to assess changes in validated patient-reported outcome measures (PROMs) and CBMP clinical safety in patients with osteoarthritis. A prospective case series from the UK Medical Cannabis Registry was analyzed. Primary outcomes were changes in the Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ2), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Single-Item Sleep Quality Scale (SQS) at 1-, 3-, 6-, and 12-month follow-ups from baseline. Common Terminology Criteria for Adverse Events v.4.0 was used for adverse event (AE) analysis. Statistical significance was defined as p < 0.050. Seventy-seven patients met inclusion criteria. CBMP initiation correlated with BPI pain severity (p = 0.004), pain interference (p = 0.005), and MPQ2 (p = 0.017) improvements at all follow-ups compared to baseline. There were improvements in the EQ-5D-5L index (p = 0.026), SQS (p < 0.001), and GAD-7 (p = 0.038) up to 6 and 3 months, respectively. Seventeen participants (22.08%) recorded 76 mild AEs (34.86%), 104 moderate AEs (47.71%), and 38 severe AEs (17.43%). Though causality cannot be assumed in this observational study, results support development of randomized control trials for osteoarthritis pain management with CBMPs.

Validation of Biomarkers and Patient-Reported Outcome Measures to Improve the Diagnosis and Treatment of Eustachian Tube Dysfunction

Patients who suffer from Eustachian tube dysfunction (ETD) experience a significant decline in quality of life. To enhance patient outcomes, it is crucial to establish an accurate diagnosis, assess treatment effectiveness, and evaluate the severity of the condition. Substantial progress has recently been made in identifying biomarkers (BMs) and developing ETD clinical outcome assessments (COAs). This study examines the current state of BMs and COAs in ETD, including the methods evaluated historically and their potential clinical applications. The research in this area emphasizes the importance of using objective measures, such as middle ear pressure (MEP) and patient-reported outcome measures (PROMs), for diagnosing and evaluating ETD. Further, I discuss how electronic PROMs (ePROMs) and other digital health technologies can guide the development of innovative PROMs that ETD. Despite significant advances in COAs for ETD, much work remains to validate and improve them before their implementation in clinical practice. There has been less focus on vertigo as a symptom in recent assessments of ETD, suggesting that further examination of this aspect is needed. By validating BMs and COAs for ETD, we could enhance long-term patient outcomes and quality of life through improved diagnostic accuracy and evaluation of treatment efficacy.

Remote Monitoring and Data Collection for Decentralized Clinical Trials

Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies. To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials. The Bloomberg New Economy International Cancer Coalition, composed of patient advocacy, industry, government regulator, and academic medical center representatives, developed a survey directed to global biopharmaceutical companies of the coalition from October 1 through December 31, 2022, with a focus on registrational clinical trials. The data for this survey study were analyzed between January 1 and 31, 2023. Adoption of decentralized clinical trial technologies. The survey measured (1) outcomes of different remote monitoring and data collection technologies on patient centricity, (2) adoption of these technologies in oncology and all therapeutic areas, and (3) barriers and facilitators to adoption using descriptive statistics. All 8 invited coalition companies completed the survey, representing 33% of the oncology market by revenues in 2021. Across nearly all technologies, adoption in oncology trials lags that of all trials. In the current state, electronic diaries and electronic clinical outcome assessments are the most used technology, with a mean (SD) of 56% (19%) and 51% (29%) adoption for all trials and oncology trials, respectively, whereas visits within local physician networks is the least adopted at a mean (SD) of 12% (18%) and 7% (9%), respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 of the 11 technologies surveyed. Furthermore, digitally enabled recruitment, local imaging capabilities, and local physician networks were identified as technologies that could be most effective for improving patient centricity in the long term. These findings may help to galvanize momentum toward greater adoption of enabling technologies to support a new paradigm of trials that are more accessible, less burdensome, and more inclusive.

Exploring the Content Validity of the Unified Wilson Disease Rating Scale: Insights from Qualitative Research.

Wilson disease (WD) is a rare metabolic disorder of impaired copper transport manifesting in hepatic, neurological, and psychiatric symptoms. To evaluate the clinical symptoms of WD in clinical trials, a group of clinicians created the Unified Wilson Disease Rating Scale (UWDRS). Content validity of this scale has not been established. The aim of this study was to evaluate the content validity of the UWDRS PartII from the patient perspective. This study utilized multiple qualitative research methods including concept elicitation interviews, concept/instrument mapping, and cognitive debriefing interviews. Concept elicitation interviews with a sample of patients with WD and one or more neurological signs/symptoms identified several signs, symptoms, and impacts related to neurological dysfunction, strengthening our understanding of the importance of the neurological aspects of the WD patient experience. Mapping neurological concepts to PartII and III items of the UWDRS showed complete coverage of all salient neurological concepts and near complete coverage of all neurological concepts reported by patients in concept elicitation interviews. Item debriefing of PartII of the UWDRS revealed that patients generally found the items clear and personally relevant to their experience with WD. Overall, the findings from this study provide evidence for the content validity of the UWDRS PartII and supportive evidence for the content validity of PartIII. The UWDRS should be used in conjunction with additional clinical outcomes assessments, specifically those evaluating the hepatic and psychiatric signs/symptoms of WD, to provide a comprehensive evaluation of the WD patient experience.

Experimentally Induced Reductions in Alcohol Consumption and Brain, Cognitive, and Clinical Outcomes in Older Persons With and Those Without HIV Infection (30-Day Challenge Study): Protocol for a Nonrandomized Clinical Trial.

Both alcohol consumption and HIV infection are associated with worse brain, cognitive, and clinical outcomes in older adults. However, the extent to which brain and cognitive dysfunction is reversible with reduction or cessation of drinking is unknown. The 30-Day Challenge study was designed to determine whether reduction or cessation of drinking would be associated with improvements in cognition, reduction of systemic and brain inflammation, and improvement in HIV-related outcomes in adults with heavy drinking. The study design was a mechanistic experimental trial, in which all participants received an alcohol reduction intervention followed by repeated assessments of behavioral and clinical outcomes. Persons were eligible if they were 45 years of age or older, had weekly alcohol consumption of 21 or more drinks (men) or 14 or more drinks (women), and were not at high risk of alcohol withdrawal. After a baseline assessment, participants received an intervention consisting of contingency management (money for nondrinking days) for at least 30 days followed by a brief motivational interview. After this, participants could either resume drinking or not. Study questionnaires, neurocognitive assessments, neuroimaging, and blood, urine, and stool samples were collected at baseline, 30 days, 90 days, and 1 year after enrollment. We enrolled 57 persons with heavy drinking who initiated the contingency management protocol (mean age 56 years, SD 4.6 years; 63%, n=36 male, 77%, n=44 Black, and 58%, n=33 people with HIV) of whom 50 completed 30-day follow-up and 43 the 90-day follow-up. The planned study procedures were interrupted and modified due to the COVID-19 pandemic of 2020-2021. This was the first study seeking to assess changes in brain (neuroimaging) and cognition after alcohol intervention in nontreatment-seeking people with HIV together with people without HIV as controls. Study design strengths, limitations, and lessons for future study design considerations are discussed. Planned analyses are in progress, after which deidentified study data will be available for sharing. ClinicalTrials.gov NCT03353701; https://clinicaltrials.gov/study/NCT03353701. DERR1-10.2196/53684.

Effects of Real-Time Feedback Methods on Static Balance Training in Stroke Patients: A Randomized Controlled Trial.

The purpose of this study was to investigate the effects of real-time feedback methods on static balance training in stroke patients. There are two types of real-time feedback methods, as follows: one is Knowledge of Result (KR), and the other is Knowledge of Performance (KP). Thirty stroke patients participated in this study and were randomly assigned to the KR group (n = 15) or the KP group (n = 15). All of the groups underwent real-time feedback training for four weeks (30 min per session, five sessions per week). The primary outcomes were sway length, sway velocity, and area 95%, which were assessed before and after the intervention. The secondary outcomes included the Berg Balance Scale, the Fugl Meyer Assessment for Lower Extremity, the Postural Assessment Scale for Stroke Trunk Impairment Scale, and the Fall Efficacy Scale. A group × time interaction was assessed using two-way ANOVA with repeated measures. There was a significant increase over time in all outcomes (p < 0.05). Significant differences were observed for a group × time interaction in sway length and area 95% (p < 0.05). Real-time feedback training for static balance enhanced stroke patients' static balance abilities, clinical outcome assessments, and promoted self-efficacy against falls.

Proximal humerus open reduction internal fixation with and without biceps tenodesis: assessment of early clinical outcomes

BackgroundThe role of biceps tenodesis (BT) during open reduction and internal fixation (ORIF) of proximal humerus fractures (PHF) remains unclear. A subset of patients undergoing ORIF have persistent pain with unclear etiology. The purpose of our study was to compare outcomes of ORIF of proximal humerus fractures with and without concomitant biceps tenodesis (BT). We hypothesize patients undergoing biceps tenodesis at the time of ORIF will have improved patient-reported outcome scores with fewer secondary procedures related to treatment of the biceps. MethodsIn this retrospective cohort study, all patients undergoing ORIF for a PHF at a single level one trauma center from January 2019 to June 2022 were reviewed. Patients under the age of 18 were excluded. Primary outcomes were PROMIS physical function, depression, and pain interference scores at 5 time points up to final follow-up. Secondary outcomes included total operative time, complications, subsequent procedures, steroid injections, and range of motion. Chi-square tests were performed for categorical values and paired t-tests for continuous variables. Results71 patients met inclusion criteria: 41 undergoing ORIF without BT, and 30 undergoing ORIF with BT. Average follow-up was 11 months. There were no statistically significant differences in patient demographics between groups. There were no differences in PROMIS scores at any time point postoperatively. At final follow-up patients in the ORIF with BT group had higher forward flexion than those who did not undergo BT (142 vs. 123 degrees, respectively, p < .02). There were no differences in surgical time, revision rates, postsurgical complications, or postoperative injections between groups. ConclusionBiceps tenodesis performed during ORIF of PHFs did not result in significantly different functional or patient-reported outcomes between groups, except for greater forward flexion at final follow-up. Although BT was done more commonly in severe PHFs, patients in both groups had similar rates of subsequent biceps-related procedures and revision surgery.

An assessment of clinical outcomes of medication abortion without pretreatment ultrasonography in Planned Parenthood, United States, 2020–2021

ObjectivesRoutine ultrasound before medication abortion (MAB) may create an impediment to expanding abortion access. This study examines clinical outcomes of MAB without pretreatment ultrasound evaluation at Planned Parenthood health centers in multiple states. Study designWe conducted a secondary analysis of data from 23 US-based Planned Parenthood affiliates that provided MAB without pretreatment ultrasound for eligible patients from March 2020 to December 2021. Affiliates aggregated electronic health record data from MABs at ≤77 days gestation (based on self-report of last menstrual period) without a pretreatment ultrasound (N = 18,041). Among MABs with known outcomes (N = 9821), we calculated the incidence rates and 95% confidence intervals (CI) for completed abortion, ongoing pregnancy, subsequent procedure, emergency department/hospital visits associated with MAB, ectopic pregnancies, and gestational duration greater than 77 days. ResultsAmong MABs with known outcomes, 96.3% had a complete abortion (95% CI = 95.9%–96.7%), and 2.0% had an ongoing pregnancy (95% CI = 1.7%–2.3%). Four percent had a subsequent procedure (95% CI = 3.6%–4.4%), and 2.3% had a documented emergency department/hospital visit (95% CI = 2.0%–2.6%). Less than 1% had a confirmed ectopic pregnancy (0.15%, 95% CI = 0.09%–0.25%) and had a gestational duration later identified to be greater than 77 days (0.13%, 95% CI = 0.05%–0.29%). ConclusionsOur calculated incidence rates of clinical outcomes align with rates from the previous literature on MAB and from the emerging literature on MAB without pretreatment ultrasonography. Findings from this analysis suggest that MAB without pretreatment ultrasound is safe and effective for eligible patients. ImplicationsThis large US study found that medication abortion without pretreatment ultrasonography results in similar clinical outcomes to prepandemic models that include pretreatment ultrasonography. Medication abortion without a pretreatment ultrasound may be adopted by abortion providers seeking to expand options for their patients as access to abortion continues to erode.

Evaluating mFARS in pediatric Friedreich's ataxia: Insights from the FACHILD study.

Friedreich ataxia (FRDA) is a rare genetic disorder caused by mutations in the FXN gene, leading to progressive coordination loss and other symptoms. The recently approved omaveloxolone targets this condition but is limited to patients over 16 years of age, highlighting the need for pediatric treatments due to the disorder's early onset and more rapid progression in children. This population also experiences increased non-neurological complications; the FACHILD study aimed to augment and expand the knowledge about the natural history of the disease and clinical outcome assessments for trials in children in FRDA. The study enrolled 108 individuals aged 7-18 years with a confirmed FRDA diagnosis, with visits occurring from October 2017 to November 2022 across three institutions. Several measures were introduced to minimize the impact of the COVID-19 pandemic, including virtual visits. Outcome measures centered on the mFARS score and its subscores, and data were analyzed using mixed models for repeated measures. For context and to avoid misinterpretation, the analysis was augmented with data from patients enrolled in the Friedreich's Ataxia Clinical Outcome Measures Study. Results confirmed the general usefulness of the mFARS score in children, but also highlighted issues, particularly with the upper limb subscore (FARS B). Increased variability, limited homogeneity across study subgroups, and potential training effects might limit mFARS application in clinical trials in pediatric populations. The FARS E (Upright Stability) score might be a preferred outcome measure in this patient population.

An epidemiological investigation of high-risk infants for Respiratory Syncytial Virus infections: a retrospective cohort study

BackgroundRespiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context.MethodsThis retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described.ResultsA total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use.ConclusionsThe assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.

Abstract 6299: Psychometric evaluation of the FACIT-SP 12 in a primary brain tumor patient population

Abstract Spirituality is a social determinant of health associated with psychosocial adjustment to serious illnesses including cancer but is not often assessed in clinical care. Here we perform psychometric evaluation of a tool developed to report spiritual well-being in chronic illness in a cohort of 248 patients with primary brain tumors (PBT) enrolled in a natural history study (NCT02851706, PI: T. Armstrong). Participants completed the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-SP 12) as part of yearly clinical outcome assessments. Total score, Meaning/Peace and Faith scores were calculated. Internal consistency (Cronbach’s alpha) and construct validity (principal components analysis with varimax rotation) evaluated psychometric properties of the FACIT-SP 12; one-way ANOVAs, one-sample t-test and Wilcoxon signed rank tests evaluated group differences (sig. p&amp;lt;0.05) on patient report of spirituality/beliefs including belief in god(s)/higher power, being religious, and prayer and in comparison to scores of previously reported studies. Participants were majority male (57%), white (79%) with high grade tumor (59%) and a median age of 48 (range: 20-82). Seven different religions were reported (majority Christianity [55%]) but also spiritual non-religious (9%), no beliefs (13%), and 6% preferring not to answer. The principal components analysis confirmed the original 2 factor solution (Meaning/Peace and Faith) and explained 66.8% of the variance (KMO =0.87, 43% of residuals &amp;lt; 0.05), with one item not loading cleanly on either factor (“I know that whatever happens with my illness, things will be okay”). Cronbach’s alphas were 0.90, 0.90, and 0.89, for the total, Meaning/Peace, and Faith scales, respectively. For all three spiritual/belief questions, patients who responded “yes” had higher total and faith scores than those who responded “no"; but not in the Meaning/Peace score when reporting religion (p=0.108). This cohort reported lower total scores (mean=32.5), Meaning/Peace scores (mean=23.4, median=24.0) and Faith scores (mean=9.2, median=10.0) compared to the initial validation in other solid tumors and HIV/AIDs (means=38.5, 25.2, 13.6, respectively) and to a smaller, less diverse PBT sample (medians: Meaning/Peace=25.8, Faith=14.0). The FACIT-SP 12 demonstrated internal consistency and construct validity, with lower scores in comparison to populations in prior studies. More diverse belief systems than previously reported may contribute to differences among studies. Future analysis should explore the increased percentage of “prefer not to answer” respondents compared to earlier reports, associations with clinical and self-reported outcomes including symptoms and quality of life, evaluation of illness-related factors that contribute to poor spiritual well-being, and a longitudinal look at spiritual well-being. Citation Format: Elizabeth Vera, Byram Ozer, Alvina Acquaye-Mallory, Valentina Pillai, Anna Choi, Ewa Grajkowska, Tricia Kunst, Hope Miller, Kimberly Reinhart, Terri S. Armstrong, Macy Stockdill. Psychometric evaluation of the FACIT-SP 12 in a primary brain tumor patient population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6299.

Assessment of Clinical and Patient-Centered Outcomes in Nonsurgical Periodontal Therapy.

Aim The study was conducted to assess the clinical and patient-centered outcomes among the patients who had undergone nonsurgical periodontal therapy (NSPT). Methodology The participants for this study were 40 individuals with generalized chronic periodontitis. Numerous clinical parameters including clinical attachment level (CAL), probing pocket depth (PPD), plaque index (PI), and gingival index (GI) were evaluated along with the administration of a customized questionnaire before and after three months of therapy to evaluate patient-centered outcomes. Results Clinical parameters showed significant (p < 0.05) improvement post-NSPT. There was 100% satisfaction in few patient-centered outcomes such as bleeding gums, bad breath, food entrapment, and mobility. Conclusion A significant improvement in the clinical parameters does not guarantee improvement in patient-centered outcomes. Achieving the improvement in patient-centered outcomes can improve the overall quality of life (QOL), marking this a holistic treatment.