Multiple Clinical Measures Research Articles

Knowledge-guided Deep Temporal Clustering for Alzheimer's Disease Subtypes in Completed Clinical Trials.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder with varied patient progression. We aim to test the hypothesis that AD patients can be categorized into subgroups based on differences in progression. We leveraged data from three randomized clinical trials (RCTs) to develop a knowledge-guided, deep temporal clustering (KG-DTC) framework for AD subtyping. This model combined autoencoders for contextual information capture, k-means clustering for representation formation, and clinical outcome classification for clinical knowledge integration. The derived representations, encompassing demographics, APOE genotype, cognitive assessments, brain volumes, and biomarkers, were clustered using the Gaussian Mixture Model to identify AD subtypes. Our novel KG-DTC framework was developed using placebo data from 2,087 AD patients across three solanezumab clinical trials (EXPEDITION, EXPEDITION2, and EXPEDITION3), achieving high performance in outcome prediction and clustering. The KG-DTC model demonstrated superior clustering structures, especially when combined with k-means clustering loss. External validation with independent clinical trial data showed consistent clustering results, with a 0.33 silhouette score for three clusters. The model's stability was confirmed through a leave-one-out approach, with an average adjusted Rand Index around 0.945. Three distinct AD subtypes were identified, each exhibiting unique patterns of cognitive function, neurodegeneration, and amyloid beta levels. Notably, Subtype 3 (S3) showed rapid cognitive decline across multiple clinical measures (e.g., 0.64 in S1 vs. -1.06 in S2 vs. 15.09 in S3 of average ADAS total change score, p<.001). This innovative approach offers promising insights for understanding variability in treatment outcomes and personalizing AD treatment strategies.

Evaluation of Analgesic Drug Therapy for Postoperative Pain Management in Cardiovascular Surgery

BackgroundCardiovascular surgery is usually associated with higher degree of postoperative pain, affecting the patient's physical recovery. Multiple clinical measures have been taken to avoid overuse of opioid for postoperative pain management, which led to the development of clinical pathways for analgesic drug treatment using a multimodal approach. ObjectiveTo evaluate the effectiveness and safety of a multimodal postoperative analgesic drug pathway (ADP) for the pain management following cardiovascular surgery. MethodsThis retrospective, controlled, non-randomized study evaluated postoperative ADP in patients undergoing cardiovascular surgery in a tertiary general hospital in Qingdao, China. Effectiveness and safety outcomes were compared before and after the implementation of ADP. Outcome indicators include postoperative pain scores, consumption of opioids in analgesic pumps and incidence of adverse events. ResultsPatients who underwent cardiovascular surgery from September to November 2021 before the implementation of ADP (N = 193) and from September to November 2022 after the implementation of ADP (N = 218) were enrolled. Pain scores were reduced on day 1, 3 and 5 after surgery and in mild pain, the reduction was most significant (P < 0.001). Opioid in analgesic pumps consumption was also significantly reduced and decreased incidence of adverse events such as nausea and vomiting (P = 0.026), respiratory inhibition (P = 0.027), and dizziness and headache (P = 0.028) were noted in cardiovascular surgery patients after ADP implementation. ConclusionsImproved effectiveness and safety were observed following the implementation of ADP. Multimodal analgesic ADP methodology can be effectively used for the postoperative pain management of cardiovascular surgery patients.

Open-Label Sulforaphane Trial in FMR1 Premutation Carriers with Fragile-X-Associated Tremor and Ataxia Syndrome (FXTAS).

Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60-88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.

Establishing the role of muscle ultrasound as an imaging biomarker in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disease, that causes weakness and wasting of skeletal muscles. In this cross-sectional cohort-study on FSHD patients, we assessed muscle ultrasound findings and their relation to clinical outcome measures, evaluating the role of ultrasound as biomarker in FSHD. We included 115 genetically confirmed FSHD patients (52% males, age-range 22–80 years). They were subjected to a standardized muscle ultrasound protocol of seven truncal and upper- and lower extremity muscles bilaterally. Muscle images were scored using the Heckmatt scale. Muscle echogenicity was quantified using z-scores. Compound echogenicity and Heckmatt scores were calculated. Nearly all patients (94%) had one or multiple muscles with an increased echogenicity z-score. The trapezius muscle was most severely affected, followed by the rectus femoris muscle. Both compound ultrasound scores strongly with multiple clinical outcome measures (ρ 0.68–0.79, p < 0.001). While most muscles showed a high level of agreement between the echogenicity z-score and Heckmatt score (>95%), the tibialis anterior and gastrocnemius muscle showed lower levels of agreement (82 and 92%). In conclusion, our study confirms the use of muscle ultrasound as clinical severity biomarker and provides a solid base for future longitudinal studies to establish ultrasound as a monitoring biomarker in FSHD.

Dynamic and static changes of amplitude of low-frequency fluctuations in anti‑N‑methyl‑D‑aspartate receptor encephalitis.

Previous neuroimaging research has examined static local brain activity changes in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. However, the dynamic properties of local brain activity in anti-NMDAR encephalitis remain unknown. This study used a combination of the amplitude of low-frequency fluctuation (ALFF) method and a sliding-window dynamic analysis approach to examine the time-varying local brain activity changes in anti-NMDAR encephalitis. Results showed that patients with anti-NMDAR encephalitis exhibited increased dynamic ALFF (dALFF) variability in the left inferior occipital gyrus compared to healthy controls (HCs), while the patients exhibited decreased sALFF in widespread regions, including the left inferior frontal gyrus, left medial frontal gyrus, bilateral putamen, left medial superior frontal gyrus. dALFF had superior classification performance in distinguishing anti-NMDAR encephalitis patients from HCs over sALFF, but sALFF was correlated with multiple clinical and neuropsychological measures. These findings may shed light on anti-NMDAR encephalitis brain dysfunction from the perspective of dynamic local brain activity. sALFF and dALFF analyses provide complementary information, emphasizing the potential usefulness of combining sALFF and dALFF in elucidating the neuropathological mechanisms of autoimmune encephalitis and may ultimately inform future disease diagnosis.

Differences in Mortality and Sepsis-Associated Organ Dysfunction between Surgical and Non-Surgical Sepsis Patients.

(1) Background: Patients with sepsis following surgical intervention may exhibit fundamental distinctions from those experiencing sepsis without prior surgery. Despite the potential clinical importance of distinguishing these two sepsis subpopulations, dissimilarities, particularly in outcome, between surgical and non-surgical patients have been subject to limited scientific investigations in the existing literature. This study aimed to investigate the differences in mortality and sepsis-associated organ dysfunction between these two groups. (2) Methods: A retrospective analysis was conducted using data from a large cohort of prospectively enrolled patients with sepsis (n = 737) admitted to three intensive care units at University Medical Center Goettingen; patients were categorized into surgical (n = 582) and non-surgical sepsis groups (n = 155). The primary outcomes assessed were 28- and 90-day mortality rates, and secondary endpoints were multiple clinical parameters and measures of sepsis-associated organ dysfunction. (3) Results: Non-surgical patients presented a significantly higher 90-day mortality (37%) compared to surgical sepsis patients (30%, p = 0.0457). Moreover, the non-surgical sepsis group exhibited increased sepsis-associated organ dysfunction, as evidenced by higher average SOFA scores (p < 0.001), elevated levels of serum Procalcitonin (p = 0.0102), and a higher utilization of organ replacement therapies such as ventilation (p < 0.001), vasopressor treatment (p < 0.001), and renal replacement therapy (p = 0.0364). Additionally, non-surgical sepsis patients had higher organ-specific SOFA respiratory (p < 0.001), cardiovascular (p < 0.001), renal (p < 0.001), coagulation (0.0335), and central nervous system (p = 0.0206) subscores. (4) Conclusions: These results suggested that patients with non-surgical sepsis may face distinct challenges and a higher risk of adverse outcomes compared to patients with sepsis following surgical intervention. These findings have important implications for clinical decision-making, patient management, and resource allocation in sepsis care.

Dysregulated immune networks define distinct respiratory phenotypes of post-acute sequelae of COVID-19

Abstract Long-haul respiratory symptoms are common following severe COVID-19 illness; however, the immune mechanisms contributing to post-acute sequelae of COVID-19 (PASC) remain enigmatic. A comprehensive 2-year longitudinal immune assessment was performed in a cohort of PASC patients receiving pulmonary follow-up care (n=110) by analyzing circulating immune cells using spectral flow cytometry, as well as assessment of virus-specific T cell frequencies, serum antibodies, and plasma mediators. Novel unsupervised machine-learning workflows were used to analyze and integrate multiple clinical and immune measures. Our approach identified discrete respiratory phenotypes according to lung physiology measures that defined the degree of lung fibrosis and its severity. Notably, severe respiratory phenotypes were characterized by immune dysregulation of both innate and adaptive cellular components, including lower ILC-3-like cells and higher activated CD4+ and CD8+ T cells in the blood. On the other hand, all respiratory phenotypes displayed a marked loss of naïve CD8+ T cells and unswitched memory B cells compared to healthy individuals. Spike- and nucleoprotein-specific CD4+ and CD8+ T cells were more abundant in severe respiratory phenotypes. Overall, T cell-derived inflammatory cytokines, along with chemokine receptors and their relationships to cognate ligands, pointed to sustained lung-homing of pathogenic effector cells in fibrotic phenotypes. Integration of high-dimensional data defined discrete cellular and molecular immune networks that provide unconventional and novel mechanistic insight into pulmonary complications post-COVID-19. UO1AI125056 R21 AI160334

Targeted Therapy for SLE-What Works, What Doesn't, What's Next.

For many years, the failure of randomized controlled trials (RCTs) has prevented patients with systemic lupus erythematosus (SLE) from benefiting from biological drugs that have proved to be effective in other rheumatological diseases. Only two biologics are approved for SLE, however they can only be administered to a restricted proportion of patients. Recently, several phase II RCTs have evaluated the efficacy and safety of new biologics in extra-renal SLE and lupus nephritis. Six drug trials have reported encouraging results, with an improvement in multiple clinical and serological outcome measures. The possibility of combining B-cell depletion and anti-BLyS treatment has also been successfully explored.

Predictors of symptom severity and change among youth in trauma-informed residential care

BackgroundTrauma-informed residential care is an intensive intervention setting for youth, but research on its effectiveness is limited and yields mixed findings. ObjectivesThe study aims were to; 1) evaluate change over time of mental health (MH) symptoms over 21 months of trauma-informed residential care, and 2) examine the influence of demographic and risk factor variables (e.g. age, gender, trauma and placement history) on baseline symptoms and treatment response. ParticipantsA sample of 547 youth ages 12 to18 in trauma-informed residential care (M age = 15.84 (SD = 1.56), 43.2 % male) were examined, with notable attrition over the study period. MethodLatent curve analysis (LCA) was used to estimate MH symptom severity at intake and change during 21 months (8 assessments total, intake and every 3 months) of care. ResultsTrauma-informed residential care was associated with significant reductions in symptoms of PTSD (d = −0.76), depression (d = −0.59), dissociation (d = −0.60), psychological dysregulation (d = −0.94), and externalizing (d = −0.31), but not internalizing (d = 0.01) problems. Females had greater symptoms at intake across multiple indicators and showed equivalent or greater treatment response than males, although both groups improved. Neither cumulative trauma nor previous placement were associated with attenuated treatment response, but trauma history was positively associated with severity of multiple clinical measures at intake. ConclusionsTrauma-informed residential treatment can lead to reductions in clinical symptoms, even among multiply trauma-impacted youth. The extent of youth's trauma history did not negatively influence treatment response.

Effect of integrated management bundle on 1-year overall survival outcomes and perioperative outcomes in super elderly patients aged 90 and over with hip fracture: non-concurrent cohort study

BackgroundDue to concomitant factors like frailty and comorbidity, super elderly (≥90 years) patients with hip fracture differ from patients aged 65–89 years in perioperative complications and mortality. The integrated management bundle referred to bundled application of multiple clinical measures. The aim of this study was to analyze effect of integrated management bundle on 1-year overall survival and perioperative outcomes in super elderly patients with hip fracture, with multidisciplinary management group serving as the control group.MethodsIn this retrospective cohort study, super elderly patients with hip fracture were included from Jan 2017 to Nov 2020. Patients were retrospectively divided to multidisciplinary management group and integrated management bundle group. The primary outcome was 1- year overall survival, and the secondary outcome was perioperative outcomes. Kaplan-Meier methods was used to compare survival probability. Multivariable Cox’s modeling was used to explain the effect of integrated bundle on 1-year overall survival adjusted for confounders. The perioperative outcomes including complications and in-hospital data of two groups were compared. The multivariable logistic regression was used to explain the effect of integrated bundle on the occurrence of perioperative complications adjusted for confounders. Prognostic factors related to survival was identified by multivariable Cox’s regression analysis.ResultsNinety-seven patients comprised multidisciplinary management group, and 83 comprised integrated management bundle group. The Kaplan–Meier plots showed that the survival probability of integrated management bundle group was significantly better than multidisciplinary management group (HR:0.435, 95%CI:0.207–0.914, P = 0.039). Multivariable analysis after adjustment for confounders showed a 42.8% lower incidence of mortality integrated management bundle group than multidisciplinary management group (HR:0.428, 95%CI:0.186–0.986, P = 0.046). Incidence of hypoproteinemia, and electrolyte disturbance in integrated management bundle group was significantly lower than multidisciplinary management group (all P < 0.05). In addition, significant reduction was observed in length of stay (P < 0.05) in integrated management bundle group. Multivariable logistic regression showed integrated management bundle was independent protective factor of hypoproteinemia, and electrolyte disturbance. mECM score ≥ 6 and ASA score > 2 were independent risk factors of overall survival (HR: 1.940, 95%CI: 1.067–3.525,P = 0.030; HR: 2.281, 95%CI: 1.113–4.678,P = 0.024).ConclusionsThe integrated management bundle improved 1-year overall survival and played positive effects in improving perioperative outcomes. It might be a more suitable management modality for super elderly patients with hip fracture.

Presurgical temporal lobe epilepsy connectome fingerprint for seizure outcome prediction.

Temporal lobe epilepsy presents a unique situation where confident clinical localization of the seizure focus does not always result in a seizure-free or favourable outcome after mesial temporal surgery.In this work, magnetic resonance imaging derived functional and structural whole-brain connectivity was used to compute a network fingerprint that captures the connectivity profile characteristics that are common across a group of nine of these patients with seizure-free outcome. The connectivity profile was then computed for 38 left-out patients with the hypothesis that similarity to the fingerprint indicates seizure-free surgical outcome. Patient profile distance to the fingerprint was compared with 1-year seizure outcome and standard clinical parameters. Distance to the fingerprint was higher for patients with Engel III–IV 1-year outcome compared with those with Engel Ia, Ib-d, and II outcome (Kruskal–Wallis, P < 0.01; Wilcoxon rank-sum pcorr <0.05 Bonferroni-corrected). Receiver operator characteristic analysis revealed 100% sensitivity and 90% specificity in identifying patients with Engel III–IV outcome based on distance to the fingerprint in the left-out patients. Furthermore, distance to the fingerprint was not related to any individual clinical parameter including age at scan, duration of disease, total seizure frequency, presence of mesial temporal sclerosis, lateralizing ictal, interictal scalp electroencephalography, invasive stereo-encephalography, or positron emission tomography. And two published algorithms utilizing multiple clinical measures for predicting seizure outcome were not related to distance to the fingerprint, nor predictive of seizure outcome in this cohort. The functional and structural connectome fingerprint provides quantitative, clinically interpretable and significant information not captured by standard clinical assessments alone or in combinations. This automated and simple method may improve patient-specific prediction of seizure outcome in patients with a clinically identified focus in the mesial temporal lobe.

Family Reported Outcome Measures and Patient Reported Outcome Measures in Multiple Myeloma Patients

Background: Multiple myeloma (MM) is one of the most common hematological malignancies. The disease is characterized by multiple symptoms resulting from the disease itself, from complications related to therapy, and as a result of the involvement of other organ systems. MM influences various aspects of patient's and family's lives. Therefore, there is a need to better understand the balance between disease control and symptoms management.Objectives: The main goal of this study is to emphasize the power and importance of Patient Reported Outcome Measures (PROMs) and Family Reported Outcome Measures (FROMs) as additional tools for patient assessment.This study evaluated the correlation between Patient Reported Outcome Measures (PROMs) and Family Reported Outcome Measures (FROMs) and disease evaluation according to the International Myeloma Working Group (IMW) response criteria in active myeloma patients. A comparison between patient and family reporting (PROMs & FROMs) and the staging of the disease according to the revised international staging system (R-ISS) was done. In addition, this study examined the confounders that may explain the relationship between PROMs and FROMs and disease evaluation.Methods: This is a quantitative, prospective, observational and longitudinal study of active patients with MM. After receiving Carmel Institutional Review Board approval to conduct the study, we enrolled fifty seven MM patients, the participants completed questionnaires of PROMs and FROMs at intervals of 3 months for one year. In addition, we monitored multiple clinical measures of patient response to treatment.A descriptive analysis of the research variables has been performed; differences between the PROMs/FROM and clinical variables analyzed by Pearson correlation, comparing PROMs/FROMs mean at the beginning of the study with the results at 3, 6, 9 and 12 months . A mixed regression model was used to examine the predictive ability of the study. In other words, the ability of Patient/Family Reported Outcome to predict the disease evaluation.Sample size was calculated using Win-Pepi software, using 5% significance and 80% power. For a coefficient of 0.4 between Patient and Family Reported Outcome and MM clinical evaluations, the minimum sample size required is 47 patients, for a coefficient of 0.35, the minimum sample size required is 62 patients. for a coefficient of 0.50, the minimum sample size required is 37 patients. This study recruited a sample size of 57 patients.Results - Fifty-seven patients participated in this study. After 3 months of treatment, a better disease evaluation was associated with improvement in disease symptoms or side effects reported by the patient. Furthermore, a better disease response was associated with a better body image scale and better future perspective. We observed a similar association after 6 and 9 months.In addition, the more the patient reported side effects or disease symptoms, the more it affects the family member (PROMs were positively correlated with FROMs). A better body image and future perspective reported by patient was associated with a lower effect on family member (PROMs were negatively correlated with FROMs)).A positive significant correlation was found between physician ranking of physical status ECOG (Eastern Cooperative Oncology Group) and the effect on family members. In other words, the worse the physical status of the patient, the more it affect the family member (in months 0,3,6 and 9).These finding were supported by the mixed model analysis, which showed a significant effect of disease symptoms, appetite loss, physical function, future perspective, and global satisfaction in prediction of clinical status.Conclusion- There is a significant relation between PROM/FROM and the typical assessment tools. This study highlights the power of PROM/FROM tools to evaluate patient from his point of view and to adjust the treatment accordingly. Finally, this study raises up the importance of continuing the research about the effect on the family member as a result of the patient disease and clinical status. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P-133: Family reported outcome measures and patient reported outcome measures in Multiple Myeloma patients

<h3>Background</h3> Multiple myeloma (MM) is one of the most common hematological malignancies. The disease is characterized by multiple symptoms resulting from the disease itself, from complications related to therapy, and as a result of the involvement of other organ systems. MM influences various aspects of patient's and family's lives. Therefore, there is a need to better understand the balance between disease control and symptoms management. <h3>Objectives</h3> The main goal of this study is to emphasis the power and importance of Patient Reported Outcome Measures (PROMs) and Family Reported Outcome Measures (FROMs) as additional tools for patient assessment. This study evaluated the correlation between Patient Reported Outcome Measures (PROMs) and Family Reported Outcome Measures (FROMs) and disease evaluation according to the International Myeloma Working Group (IMW) response criteria in active myeloma patients. A comparison between patient and family reporting (PROMs & FROMs) and the staging of the disease according to the revised international staging system (R-ISS) was done. In addition, this study examined the confounders that may explain the relationship between PROMs and FROMs and disease evaluation. <h3>Methods</h3> This is a quantitative, prospective, observational study of active patients with MM. During the study, the participants completed questionnaires of PROMs and FROMs at intervals of 3 months for one year. In addition, we monitored multiple clinical measures of patient response to treatment. Required sample size was calculated using Win-Pepi software, using 5% significance and 80% power. For a correlation of 0.4 between Patient and Family Reported Outcomes and MM clinical evaluations, the minimum sample size required is 47 patients, and for a correlation of 0.50, the minimum sample size required is 37 patients. <h3>Results</h3> Fifty-seven patients participated in this study. After 3 months of treatment, a better disease evaluation was associated with improvement in disease symptoms or side effect reported by patient. Furthermore, a better disease response was associated with a better body image scale and better future perspective. We observed a similar association after 6 and 9 months. In addition, the more the patient reported side effects or disease symptoms, the more it affects the family member (PROMs were positively correlated with FROMs). A better body image and future perspective reported by patient was associated with a lower effect on family member (PROMs were negatively correlated with FROMs). These finding was supported by the fixed model analysis, which showed a significant effect of disease symptoms, appetite loss, physical function, future perspective and global satisfaction in prediction of clinical status. <h3>Conclusion</h3> There is a significant relation between PROM/FROM and the typical assessment tools. This study highlights the power of PROM/FROM tools to evaluate patient from his point of view and to adjust the treatment accordingly.

Prognostic Modeling of Parkinson's Disease Progression Using Early Longitudinal Patterns of Change.

Predicting Parkinson's disease (PD) progression may enable better adaptive and targeted treatment planning. Develop a prognostic model using multiple, easily acquired longitudinal measures to predict temporal clinical progression from Hoehn and Yahr (H&Y) stage 1 or 2 to stage 3 in early PD. Predictive longitudinal measures of PD progression were identified by the joint modeling method. Measures were extracted by multivariate functional principal component analysis methods and used as covariates in Cox proportional hazards models. The optimal model was developed from the Parkinson's Progression Marker Initiative (PPMI) data set and confirmed with external validation from the Longitudinal and Biomarker Study in PD (LABS-PD) study. The proposed prognostic model with longitudinal information of selected clinical measures showed significant advantages in predicting PD temporal progression in comparison to a model with only baseline information (iAUC=0.812 vs. 0.743). The modeling results allowed the development of a prognostic index for categorizing PD patients into low, mid, and high risk of progression to HY 3 that is offered to facilitate physician-patient discussion on prognosis. Incorporating longitudinal information of multiple clinical measures significantly enhances predictive performance of prognostic models. Furthermore, the proposed prognostic index enables clinicians to classify patients into different risk groups, which could be adaptively updated as new longitudinal information becomes available. Modeling of this type allows clinicians to utilize observational data sets that inform on disease natural history and specifically, for precision medicine, allows the insertion of a patient's clinical data to calculate prognostic estimates at the individual case level. © 2021 International Parkinson and Movement Disorder Society.

Speech and swallowing deficits in X-Linked Dystonia-Parkinsonism

IntroductionX-linked Dystonia-Parkinsonism (XDP) is a progressive, disabling disease characterized by the devastating impairment of bulbar function, including speech and swallowing. Despite these detrimental impacts, bulbar impairments in this population are not well characterized. ObjectivesTo identify impairments in the bulbar system measured by oromotor performance in individuals with XDP relative to healthy controls. Secondarily, to detect diagnostic bulbar markers that are sensitive and specific to the initial years of XDP. MethodsThis case-control study included 25 healthy controls and 30 participants with XDP, divided into two subgroups based on the median of their disease length. Multiple clinical and instrumental oromotor tasks and measures were used to evaluate bulbar motor function. ResultsDifferences were found between both the subgroups with XDP and healthy controls on almost all measures, including maximum performance tasks such as tongue strength, alternating motion rate (AMR), and sequential motion rate (SMR) (p < 0.05). Differences were found between the XDP subgroups and the control group for the percentage of pause time during the speech, a rating of speech severity, and a swallowing task (ps < 0.05). Scores on self-reported questionnaires, tongue strength, the number of repetitions produced during an AMR, percent pause, and speech severity demonstrated good sensitivity and specificity to differentiate the initial years of XDP onset from healthy controls. ConclusionsOur findings revealed impairments across bulbar functions in participants within the first 7 years of the XDP onset. Highly sensitive and specific bulbar impairment measures were detected in instrumental and self-reported measures that are fundamental for monitoring disease.

Randomised clinical trial: adjunctive induction therapy with oral effervescent budesonide in newly diagnosed coeliac disease

The healing of the mucosal lesion in patients with coeliac disease is slow. To determine whether concurrent budesonide and gluten-free diet hasten small bowel healing and symptomatic improvement in patients with newly diagnosed coeliac disease. In a pilot, randomised, double-blind trial, effects on Marsh grading and quantitative duodenal morphometry of 10weeks' effervescent budesonide (initially 9mg/day) or placebo were assessed after 8 and 52weeks. Multiple clinical measures and adverse events were assessed. Nineteen patients were randomised to budesonide and 18 to placebo. No differences (all P>0.32) were observed for the week-8 mucosal response (Marsh 0 or 1) (budesonide: 37% vs placebo: 28%), week-8 remission (Marsh 0) (32% vs 17%), week-52 response (63% vs 44%) and week-52 remission (42% vs 33%). Likewise, the improvement from baseline in villous-height:crypt-depth ratio was not different for the treatment groups. There were no statistically significant differences in clinical measures or adverse events between the treatment groups. No corticosteroid adverse effects were observed. In a post hoc analysis of all patients, Marsh 3C was present at the diagnostic biopsy in 1/9 achieving mucosal remission at 8weeks versus 18/23 not (P<0.001) and mean villous-height:crypt-depth ratio was 1.06 (SD: 0.73) versus 0.46 (0.38) (P=0.005). In this pilot trial, induction therapy with budesonide had no significant effect on mucosal healing in patients with coeliac disease concurrently initiated on a gluten-free diet. Mucosal remission at 8weeks occurred in approximately one in four patients and was associated with less severe histological lesions at diagnosis.

AB0560 EFFECT OF DEUCRAVACITINIB ON THE PSORIATIC ARTHRITIS IMPACT OF DISEASE (PsAID) QUESTIONNAIRES 12 AND 9: ANALYSIS OF A PHASE 2 STUDY OF ACTIVE PSORIATIC ARTHRITIS

Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates IL-23, IL-12, and IFNα/β signaling. Deucravacitinib is a novel, oral selective inhibitor of TYK2 via the TYK2 regulatory domain. Phase 2 results showed deucravacitinib was efficacious and well tolerated versus placebo (PBO) in patients (pts) with active psoriatic arthritis (PsA). The Psoriatic Arthritis Impact of Disease (PsAID) questionnaire is a EULAR-developed, validated instrument designed to specifically assess the impact of PsA on health-related quality of life (HRQoL) from the pt’s perspective and is available as separate versions for clinical practice (PsAID-12) and clinical trials (PsAID-9).1Objectives:To compare the effect of deucravacitinib vs PBO on PsAID-12 and PsAID-9 responses and to assess relationships between PsAID scores and clinical and pt-reported outcome (PRO) measures.Methods:This is an ongoing, 1-year, double-blind, Phase 2 trial (NCT03881059). Pts with active PsA were randomized 1:1:1 to deucravacitinib 6 mg or 12 mg once daily, or PBO for 16 weeks (wk). PsAID-12 and PsAID-9, other PROs, and clinical response outcomes were assessed at baseline (BL) and Wk 16. Mean changes from BL in PsAID-12 and PsAID-9 total scores at Wk 16 were determined for each treatment group as well as by response outcomes (ie, achievement of response at Wk 16 for PROs and select clinical response outcomes; Table 1). Spearman correlations between PsAID-12 and PsAID-9 scores and clinical and PRO measures were also assessed.Results:203 pts were randomized and BL characteristics were similar across groups. Adjusted mean changes from BL in PsAID-12 and PsAID-9 scores at Wk 16 were significantly greater in the deucravacitinib groups vs PBO (Figure 1). Adjusted mean changes from BL in PsAID-12 and PsAID-9 scores at Wk 16 were significantly improved with deucravacitinib vs PBO in pts who achieved response for PROs, as well as PASDAS low disease activity and PASI 75 response (Table 1). Adjusted mean changes from BL were generally similar with deucravacitinib vs PBO in nonresponders. Spearman correlation analysis revealed significant correlations at BL and Wk 16 between PsAID-12 and PsAID-9 scores and clinical and PRO measures (P&lt;0.0001).Conclusion:With deucravacitinib vs PBO, PsAID-12 and PsAID-9 scores were significantly improved vs BL at Wk 16. PsAID detected additional improvements among pts achieving response for multiple other PROs and select clinical outcome measures.

Characterization of disease course and remission in early seropositive rheumatoid arthritis: results from the TACERA longitudinal cohort study.

Background:To characterise disease course and remission in a longitudinal observational study of newly diagnosed, initially treatment-naïve patients with seropositive rheumatoid arthritis (RA).Methods:Patients with early untreated seropositive RA were recruited from 28 UK centres. Multiple clinical and laboratory measures were collected every 3 months for up to 18 months. Disease activity was measured using the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI). Logistic regression models examined clinical predictors of 6-month remission and latent class mixed models characterised disease course.Results:We enrolled 275 patients of whom 267 met full eligibility and provided baseline data. According to SDAI definition, 24.3% attained 6-month remission. Lower baseline Health Assessment Questionnaire (HAQ) and SDAI predicted 6-month remission (p = 0.013 and 0.011). Alcohol intake and baseline prescribing of methotrexate with a second disease-modifying antirheumatic drug (DMARD; vs monotherapy without glucocorticoids) were also predictive. Three distinct SDAI trajectory subpopulations emerged; corresponding to an inadequate responder group (6.5%), and higher and lower baseline activity responder groups (22.4% and 71.1%). Baseline HAQ and Short Form-36 Health Survey – Mental Component Score (SF-36 MCS) distinguished these groups. In addition, a number of baseline clinical predictors correlated with disease activity severity within subpopulations. Beneficial effects of alcohol intake were found across subpopulations.Conclusion:Three distinct disease trajectory subpopulations were identified. Differential effects of functional and mental well-being, alcohol consumption, and baseline RA medication prescribing on disease activity severity were found across subpopulations. Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors. We hypothesise that biological markers collected early in disease course (within 6 months) may help patient management and better targeting of existing and novel therapies.

Modified Broström repair with suture tape augmentation for lateral ankle instability: A systematic review

BackgroundThere is increasing interest in augmentation of modified Broström repairs for lateral ankle instability with a prosthetic reconstruction using suture tape internal bracing. The aim of this study was to investigate if suture tape augmentation resulted in improved clinical and radiological outcomes compared to a standard modified Broström repair alone. MethodsA systematic review following PRISMA guidelines was undertaken. All clinical studies published in Medline, Embase, Pubmed and the Cochrane Library Database from inception until January 2020 reporting on the use of suture tape augmentation to a modified Broström repair for lateral ankle instability. Results78 studies were identified of which 10 (assessing 333 patients) met the criteria for inclusion. Mean follow up was 24.8 months (range 6–52 months). All studies showed a statistically significant improvement across multiple clinical outcome measures post-surgery in both suture tape augmentation and modified Broström groups, however there were no statistically significant inter-group differences.Pooled results suggested there may be a reduction in recurrence of instability with suture tape augmentation when compared to modified Broström repair alone (p < 0.05). Overall quality of evidence was moderate to poor with limited data to support use of suture tape augmentation. ConclusionClinical and radiographic outcomes using a suture tape internal bracing for lateral ankle instability are excellent, and are equivalent to standard treatment across multiple clinical and radiographic assessment measures. There is minimal evidence to suggest functional outcomes are better, or recurrence rates are lower than modified Broström repair alone. PROSPERO REGISTRYCRD42020169876. Level of evidenceII.

Increased Oxidative Stress Underlies Abnormal Pain Threshold in a Normoglycemic Japanese Population.

Normal-high HbA1c levels are a risk factor for attenuated pain sensation in normoglycemic subjects. It is unclear, however, what mechanisms underlie the pathogenesis of attenuated pain sensation in such a population. We, therefore, explored the relationship between oxidative stress (OS) and pain sensation in a rural Japanese population. A population-based study of 894 individuals (average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold induced by intraepidermal electrical stimulation (PINT) and clinico-hematological parameters associated with OS were evaluated. Univariate linear regression analyses revealed age, BMI, HbA1c, the OS biomarker urine 8-hydroxy-2′-deoxyguanosine (8-OHdG), systolic blood pressure, and decreased Achilles tendon reflex on the PINT scores. Adjustments for age, gender, and multiple clinical measures confirmed a positive correlation between PINT scores and urine 8-OHdG (β = 0.09, p < 0.01). Urine 8-OHdG correlated positively with higher HbA1c levels and age in the normoglycemic population. Unlike in the normoglycemic population, both inflammation and OS were correlated with elevated PINT scores in IFG subjects. OS may be a major contributing factor to elevated PINT scores in a healthy Japanese population.