Improvement In Total Score Research Articles

Effect of istradefylline on postural abnormalities in patients with Parkinson's disease: An association study of baseline postural angle measurements with changes in Unified Dystonia Rating Scale total score

In our previous study, istradefylline treatment in patients with Parkinson's disease (PD) improved postural abnormalities (PAs), as seen from a decrease in the mean Unified Dystonia Rating Scale (UDRS) total score from week 0 to week 24. A subgroup analysis based on baseline clinical characteristics investigated the association between improvement in the UDRS total score and istradefylline treatment. However, the association between an objective assessment of PAs and improvement in the UDRS total score is unclear. This ad hoc analysis investigated the association between improvement in the UDRS total score after istradefylline treatment and baseline trunk and neck angles, objective assessments of PAs, measured from patients' photographs taken in the previous study. The patients (n = 31) were stratified into groups based on the trunk forward flexion angle (TFFA), trunk lateral flexion angle (TLFA), and neck flexion angle (NFA) values at baseline. From week 0 to week 24, significant improvements in the UDRS total score were found in median percent change (−8.33% [interquartile range: −43.97, 0.00], P = 0.039) in patients with equal to or above the median TFFA values, and in median change (−‍1.50 [−9.25, 0.00], P = 0.015) and median percent change (−13.33% [−50.47, 0.00], P = 0.009) in patients with equal to or above the median TLFA values. Patients with more advanced PAs showed more consistent improvements in the UDRS total score with istradefylline. Baseline TFFA and TLFA values, which are objective values, may be useful to assess the istradefylline effectiveness in patients with PD and PAs.

Supplementation with β-hydroxy-β-methylbutyrate after resistance training in post-acute care patients with sarcopenia: A randomized, double-blind placebo-controlled trial

ObjectivesThis study aimed to evaluate the efficacy of adding β-hydroxy-β- methylbutyrate (HMB) supplementation to a 12-week exercise-based rehabilitation program in older adults with sarcopenia after discharge from a post-acute geriatric rehabilitation unit. Study designA randomized, double-blind, placebo-controlled trial with two parallel groups. The intervention group received 3 g/day of Ca-HMB and participated in a 12- week resistance training program (3 sessions/week). The control group received a placebo and followed the same training program. Main outcome measuresThe primary outcomes were the improvements of handgrip strength and physical performance assessed through the Short Physical Performance Battery (SPPB) and 4-meter gait speed; and handgrip strength. All variables were assessed at baseline, post-intervention, and 1-year follow-up. ResultsAfter completing the 12-week exercise program, the intervention group showed significant improvements in SPPB-Balance (1.3, 95 %CI 0.3 to 2.4) and total SPPB score (2.2, 95 %CI 0.4 to 4.0). Intra-group analysis demonstrated gains in the SPPB-Chair Stand (0.7 points, 95 %CI 0.0 to 1.4) and total SPPB score (2.1 points, 95 %CI 0.3 to 3.9) in the intervention group. Improvements in handgrip strength were observed in women (3.7 kg, 95 %CI: 0.2 to 7.3) at the end of the intervention, and persisted at the 1-year follow-up. ConclusionsOur findings suggest that the supplementation of 3 g/day of Ca-HMB with resistance exercise may significantly enhance muscle strength and physical performance among older women with sarcopenia after recent hospitalization. Given this study's limitations, the intervention's effectiveness cannot be drawn, and further studies are needed.

Two-Year Survivorship and Patient-Reported Outcomes of a Prospectively Enrolled Cohort of INFINITY Total Ankle Arthroplasties.

The INFINITY total ankle implant is a widely and successfully used option for total ankle arthroplasty. The purpose of this study is to assess the 2-year survivorship, complication rates, patient-reported outcomes, and radiologic findings of prospectively enrolled patients undergoing a fixed-bearing total ankle arthroplasty (TAA). This study sought to determine if factors such as traditional vs patient-specific instrumentation, preoperative degree of arthritis, deformity, or etiology of arthritis impact surgical or clinical outcomes. A total of 143 prospectively enrolled patients (148 ankles) underwent TAA with a fixed-bearing total ankle implant between 2017 and 2019 at 9 different institutions by 9 different surgeons. A total of 116 completed 2-year follow-up. Patients were stratified by instrumentation used, degree of preoperative deformity, the Canadian Orthopaedic Foot and Ankle Society (COFAS) grading system, and etiology of arthritis. Outcomes used included implant survivorship and adverse events within 2 years of surgery. Additionally, patient-reported outcomes and radiographs were collected at 6-month, 1-year, and 2-year postoperatively. PROMs used included Ankle Osteoarthritis Score (AOS), Patient-Reported Outcomes Measurement Information System (PROMIS) global health score, the Foot and Ankle Outcome Score (FAOS), and patient satisfaction (rated from excellent to poor). Implant survivorship at 2 years was 97.79%. There were 17 reoperations (11.5%), with 4 of the implants requiring revision (2.7%). Significant improvements in all PROMs were observed among all subgroups at all postoperative time points without significant variation between subgroups. Patients classified as COFAS type 2 arthritis preoperatively demonstrated significantly more improvement in FAOS Total Symptom Score at the 1- and 2-year measurements than COFAS type 3 patients at both time points. Total ankle arthroplasty with a fixed-bearing implant system is a safe and reliable treatment option for patients with end-stage arthritis regardless of degree of deformity or COFAS grading. Level II, prospective cohort study.

Prevalence of Anxiety as a Variable in Treatment Outcomes for Individuals With Chronic Refractory Cough.

Anxiety is a mental state characterized by an intense sense of tension, worry, or apprehension relative to something adverse that might happen in the future. Anxiety is a known comorbidity in cough patients, yet its prevalence among those with chronic refractory cough (CRC) is unknown. Anxiety is not typically assessed during evaluation for CRC, but treatments for CRC such as neuromodulators and behavioral cough suppression therapy (BCST) may potentially attenuate anxiety. This preliminary study investigates the potential prevalence of anxiety in CRC and its possible role in treatment outcomes. CRC patients seen in a specialty clinic at the University of Utah or the University of Montana completed the Leicester Cough Questionnaire (LCQ) pre- and post-BCST treatment. Participants were dichotomized into positive anxiety screen (PAS) and negative anxiety screen (NAS) groups based on presence or absence of documented anxiety within electronic medical records at the University of Utah and based on a Generalized Anxiety Disorder-7 score > 5 at the University of Montana. Of the 86 total participants, 37 (43%) were in the PAS group (29 females, Mage = 56 ± 13) and 49 (57%) were in the NAS group (36 females, Mage = 64 ± 14). Eighty-nine percent of CRC participants with a PAS reported a clinically meaningful improvement in LCQ total score following treatment compared to 65% of NAS participants. Furthermore, mean pre- to posttreatment change scores on the LCQ were significantly greater within the PAS group (p = .002, Cohen's d = 0.7, indicating a moderate to large effect size). This preliminary study suggests that (a) anxiety may be prevalent among those with CRC and (b) those patients who screen positive for anxiety report greater benefit from BCST.

Abstract B058: Positive changes in diet quality among African American breast cancer survivors from Moving Forward, a weight loss intervention program

Abstract Background: African American breast cancer survivors (AABCS) experience higher rates of all-cause mortality and recurrence risk compared to survivors of other races/ethnicities. Although disparities are multi-factorial, lifestyle is a key factor in cancer survivorship, comorbidity burden and quality of life. The American Cancer Society (ACS) and American Institute for Cancer Research (AICR) have set nutrition and physical activity guidelines for cancer survivors. This study examines the between and with-in group differences of diet quality and related outcomes among AABCS enrolled in Moving Forward (MF). Methods: MF was a 6-month, community-based, weight-loss intervention trial for AABCS. Participants were randomized to either an Interventionist-Guided (IG) or Self-Guided (SG) group. Both groups received educational materials to promote lifestyle changes. The IG group also received twice weekly group sessions with supervised exercise and group support. Participants completed surveys on diet quality (Block 2005 Food Frequency Questionnaires (FFQ)) and related outcomes, and fitness assessments at baseline, post-intervention and at a 12-month follow-up. Diet quality was scored using the Healthy Eating Index (HEI-2010) range 0-100, Alternative Healthy Eating Index (AHEI-2010) range 0-110, and ACS/AICR guidelines range 0-21 to measure adherence pre- and post-intervention. Results: 180 AABCS completed the FFQ at all 3 timepoints and were included in these analyses. Participants had a mean age of 57.6 ± 10.6, 40.2% were married/living with a partner, and had varied income and education levels. Participants were an average of 7.2 years from diagnosis (range 0.8-35.1 years), 99% had surgery, 78% had radiation and 74% had chemotherapy. At baseline, mean diet scores were 65.3 for HEI-2010, 56.7 for AHEI-2010, and 12.7 for ACS/AICR guidelines. Although results varied among the 3 diet indices, participants in the IG group saw significant improvements in fruit, vegetable, and whole grain consumption with decreased sugar, empty calorie, and trans fat consumption from baseline to 6 and 12 months. Both groups saw improvements in total scores for all 3 diet indices from baseline to 6 and 12 months. The SG group improved in limiting sugars and empty calories from baseline to follow-up timepoints. The IG group saw greater improvements in fruit and vegetable consumption compared to SG group in all 3 diet indices. Body Mass Index and physical activity were significantly improved in both groups but social support, self-efficacy, and perceived barriers to healthy eating were significantly improved in the IG group only. Conclusion: Overall diet quality scores were suboptimal at baseline showing a need for positive dietary change among AABCS, and a need for more evidence considering diet quality and social predictors of dietary intake in this community. Data from culturally tailored and community-based interventions like MF can be used to develop effective, sustainable strategies to improve diet quality and related outcomes in AABCS even after an intervention ends. Citation Format: Margaret Y. Tovar, Sparkle Springfield, Melinda Stolley. Positive changes in diet quality among African American breast cancer survivors from Moving Forward, a weight loss intervention program [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B058.

Impact of twice-a-day transcranial direct current stimulation intervention on cognitive function and motor cortex plasticity in patients with Alzheimer’s disease

BackgroundNon-invasive brain stimulation has improved cognitive functions in patients with Alzheimer’s disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial...

Impact of Frontline Treatment Strategy on Quality of Life in the First Decade after a Diagnosis of Marginal Zone Lymphoma

Background: Marginal Zone Lymphoma (MZL) is considered indolent but incurable, with a variety of initial treatment strategies including observation. Quality of life (QOL) can be affected by disease burden, side effects of treatment, and psychosocial effects of living with an incurable cancer. However, little is known about long-term QOL in patients with MZL. We investigated QOL at baseline (BL), and up to nine years after a diagnosis of MZL. Methods: Newly diagnosed MZL patients aged 18 years and older were prospectively enrolled within 9 months of diagnosis in the Iowa/Mayo Clinic Molecular Epidemiology Resource from 9/2002 - 6/2015. Pathology was reviewed by a hematopathologist. All MZL participants with both BL and at least one follow-up (FU) QOL questionnaire were eligible for this analysis. QOL was measured at BL and years 1-, 2-, 3-, 6- and 9-year FU with the Functional Assessment of Cancer Therapy-General (FACT-G) scale (range 0-108), which measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). Clinical data were abstracted according to a standard protocol and patients were systematically followed for events (progression, re-treatment, and death). Patients were grouped into initial management with active surveillance (observation), local/antibiotic therapy (including radiation, surgery, and anti- H. pylori therapy), or systemic therapy (including chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and comparisons were made according to initial treatment group. Results: Of 324 participants in the analysis, 59% were female, 98% were White and the median age was 63 years. For initial management, 36% (N=118) were observed, 30% (N=96) received local/antibiotic therapy and 34% (N=110) received systemic therapy. Across the initial treatment groups, there were no statistically significant differences by age, gender, or performance status, while there were differences for Ann Arbor Stage IV (observation 50%, local/antibiotic 27%, systemic 67%, p<0.001) and MALT-IPI score 2+ (observation 23%, local/antibiotic 18%, systemic 28%, p<0.001). At BL, mean FACT-G total score was 85.7 (SD 13.1), and physical, social/family, emotional, and functional WB scores were 20.3 (SD 4.2), 24.4 (SD 3.9), 18.9 (SD 3.5), 22.1 (SD 5.3); these scores were similar across initial treatment groups (all p>0.05). FACT-G total score was largely stable over time by treatment group (Panel 1). However, it declined at years 6 (mean -4.0, p<0.05) and 9 (mean -3.7, p<0.05) in the observation group (Panel 2), driven by a decline in functional WB, although this change was not significantly different from the other treatment groups. Further, in comparison with other treatment groups, local therapy was associated with a short-term 1-year improvement of FACT-G total score (mean +2.8, p=0.04), driven by improvements in both functional and emotional WB. For the subscales, we identified two major trends irrespective of treatment group: an overall improvement from BL of emotional WB at years 1 (mean +0.6, p<0.05), 2 (mean +0.7, p<0.05), 3 (+1.3, p<0.05), 6 (+1, p<0.05), and 9 (+1.3, p<0.05) and an overall decline of social/family WB at years 1 (mean -1.1, p<0.05), 2 (mean -1.7, p<0.05), 3 (-2.1, p<0.05), 6 (-2.7, p<0.05), and 9 (-2.2, p<0.05). There was no notable change from BL for physical or functional WB. Conclusions: This analysis is the first to provide prospective real-world QOL data on a longitudinal cohort of MZL patients with long follow-up. At BL, initial treatment was associated with stage and MALT-IPI score, but not QOL. Except for the transient 1-year QOL improvement in patients under local/antibiotic therapy, initial treatment groups had no impact on QOL over time. Irrespective of treatment group, emotional WB showed improvement over time, suggesting psychosocial adaptation by the patient, as it was found in aggressive lymphomas (Thompson et al., 2018). Further, emotional WB over time did not vary across treatment groups, suggesting that being initially observed did not lead to more emotional stress than being actively treated. Finally, decline in social/family WB (support from friends, family, family acceptance of illness, family communication, close to partner) suggests a need to consider interventions to patients and families to address these needs.

NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease

Nicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404.

Patient and Parent-Reported Outcomes Post-Treatment with Shmir-Based Lentiviral Gene Therapy for Sickle Cell Disease

Background: Sickle cell disease (SCD) is among the most common monogenic disorders and causes lifelong complications, including vaso-occlusive events (VOEs) and decreased quality of life (QOL). Gene therapy (GT) has emerged as a potential curative therapy for SCD, but its impact on patients' QOL remains underexplored. We previously reported preliminary safety and efficacy data on 6 patients who received autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector (Esrick et al., NEJM, 2021). Here, we report the first results of parent- and patient-reported outcomes (PROs) for 10 patients treated with BCH-BB694 up to 24 months post-infusion. Methods: We evaluated the QOL of 10 patients with severe SCD who received GT with BCH-BB694 as part of a single-center, open-label pilot study. Assessment occurred during patients' scheduled visits for safety and efficacy monitoring at baseline and months 3, 6, 12, and 24. QOL was measured using the Pediatric Quality of Life Inventory (PedsQL) self- and parent-reported questionnaires for children < 18-years old and the self-reported 36-Item Short Form Health Survey (SF-36) for adults ≥ 18-years old. Assessed domains included: physical functioning, pain, emotional functioning, social functioning, school functioning, and general health. The percent change from baseline to post-treatment score (last observation carried forward [LOCF]) was calculated with 95% confidence intervals (CI). Clinically significant improvement was defined as a score increase ≥5%. Other laboratory and clinical data collected at study timepoints included fetal hemoglobin (HbF) measured by high-performance liquid chromatography, VOEs (including vaso-occlusive pain, priapism, and acute chest syndrome), and transfusion frequency. Results: All patients demonstrated elevated HbF levels at LOCF (mean 26.9%, range 11.7-38.2%). Of 10 patients enrolled, 1 was missing baseline data and 9 had sufficient data for analysis. Patients (n=9) were aged 8-27 years at time of BCH-BB694 infusion. Baseline self-reported total scale scores (median 69.6, interquartile range [IQR] 50.1, 77.2) were consistent with baseline PedsQL scores for patients with SCD reported in the literature (median 67.4, IQR 50.0, 83.5) (Panepinto et al., J Pediatr Hematol Oncol, 2008). Average self-reported total scale scores increased at 3 months post-treatment (mean % change from baseline [95% CI]: 21% [3.3% to 38%]) and maintained at LOCF (13% [-10% to 36%]). For the 3 patient/parent pairs, parent-reported total scale scores appeared more variable, with a mean % change from baseline of -1% (95% CI: -40% to 38%) at 3 months and -17% (95% CI: -36% to 1%) at 24 months. Clinically significant self-reported improvement occurred in 8 patients (89%) for at least 1 domain and in 5 (56%) for overall QOL. The patient without baseline data reported a maximum total scale score of 100 at 24-months. Specific domains (mean % change from baseline [95% CI]) demonstrating significant improvement included: general health (7% [-11%, 25%]), physical functioning (30% [-15%, 76%]), and emotional functioning (15% [-9%, 39%]). Excluding 1 patient who had a low HbF induction associated with a low in vivo vector copy number and increase in VOEs from baseline, this cohort demonstrated decreased numbers and/or absence of VOEs post-GT (n=8), and all patients required significantly fewer transfusions. Conclusion: At most recent study visit up to 24 months post-treatment, SCD patients who had received GT with successful HbF induction (>20% in 8 patients) reported higher QOL than baseline on average. Excluding 1 patient, this cohort demonstrated improvement in at least 1 QOL domain following GT, suggesting a positive impact of GT on QOL in this group of patients with SCD. For patients <18-years, discrepancies between parent-reports and higher self-reports warrant future investigation. Few patients (n=3) did not demonstrate overall QOL total score improvement post-GT. Follow up studies may assess whether this reflects insufficient treatment response, treatment- or pre-existing disease-related morbidity, and/or need for more specific QOL assessments. An understanding of the relationship of change in QOL with VOE and/or transfusion rates will be enriched by more patients, longer follow-up, and PRO tools designed specifically for the SCD population. Larger studies are needed to fully elucidate the impact of GT on QOL in this population.

Lateral Subvastus Lateralis versus Medial Parapatellar Approach for Total Knee Arthroplasty: Patient Outcomes and Kinematics Analysis.

The conventional approach for total knee arthroplasty (TKA) is a medial parapatellar approach (MPA). We aimed to study patient outcomes and kinematics with a quadriceps sparing lateral subvastus lateralis approach (SLA). Patients with neutral/varus alignment undergoing primary TKA were consented to undergo the SLA. At 1-year postoperative, patients underwent radiostereometric analysis. Patients were administered the Short Form 12 (SF-12), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Society Score (KSS). Kinematics and outcome data were compared to a group undergoing TKA via conventional MPA. Fourteen patients underwent TKA via SLA with a mean age 71.5 ± 8.0 and mean body mass index (BMI) 31.0 ± 4.5. The MPA group had 13 patients with mean age 63.4 ± 5.5 (p = 0.006) and mean BMI 31.2 ± 4.6 (p = 0.95). The SLA resulted in a significantly more posterior medial contact point at 0 (p = 0.011), 20 (p = 0.020), and 40 (p = 0.039) degrees of flexion. There was no significant difference in medial contact point from 60 to 120 degrees, lateral contact point at any degree of flexion, or axial rotation. There was no difference in improvement in postoperative WOMAC, SF-12, KSS function, and total KSS knee scores between groups. The MPA group had a significantly greater improvement in KSS knee scores at 3 months (p < 0.001), 1 year (p = 0.003), and 2 years (p = 0.017). The SLA resulted in increased medial femoral rollback early in flexion. Although both approaches resulted in improved postoperative outcomes, the MPA group showed significantly greater improvements in KSS knee scores at 3 months, 1 year, and 2 years. Further studies are required to identify any benefits that the SLA may offer. LEVEL OF EVIDENCE: Therapeutic Level II.

Long-Term Safety and Efficacy of Perfluorohexyloctane Ophthalmic Solution for the Treatment of Patients With Dry Eye Disease: The KALAHARI Study.

The aim of this study was to assess the long-term safety and efficacy of perfluorohexyloctane (PFHO) ophthalmic drop (formerly NOV03) for treatment of dry eye disease (DED). KALAHARI was a phase 3, multicenter, single-arm, open-label extension study in patients aged 18 years or older with DED associated with Meibomian gland dysfunction who completed the randomized, double-masked, hypotonic saline-controlled GOBI study. Patients instilled 1 drop of PFHO (MIEBO, Bausch + Lomb) 4 times daily in both eyes for 52 weeks. Safety assessments included adverse events, best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure, and dilated fundoscopy. Efficacy end points included change from GOBI study baseline in total corneal fluorescein staining and eye dryness score (0-100 visual analog scale). Overall, 208 patients from GOBI (PFHO [n = 97]; saline [n = 111]) were rolled over into KALAHARI. Twenty-nine patients (13.9%) had ≥1 ocular adverse event, with most being mild or moderate in severity; the most common ocular adverse events were vitreous detachment (1.9%), allergic conjunctivitis (1.4%), blurred vision (1.4%), and increased lacrimation (1.4%). Other safety end points were unremarkable. For patients continuing PFHO from GOBI, improvements in total corneal fluorescein staining and visual analog scale dryness scores observed in GOBI were maintained throughout KALAHARI. Patients treated with saline in GOBI and switched to PFHO in KALAHARI showed improvements in total corneal fluorescein staining and visual analog scale scores by week 4 that were maintained for the rest of the study. PFHO was safe and well tolerated and maintained efficacy for improving signs and symptoms of DED in this year-long study of patients with DED associated with Meibomian gland dysfunction.

Phase 1b/2 Study Evaluating the Safety and Efficacy of Canakinumab with Darbepoetin Alfa in Patients with Lower-Risk Myelodysplastic Syndromes (MDS) Who Have Failed Erythropoietin Stimulating Agents (ESA)

Introduction: Pyroptosis is a form of inflammatory, caspase-1 dependent lytic cell death mediated by inflammasome activation and ultimately leading to enumeration of pro-inflammatory cytokines, particularly interleukin 1β (IL-1β) and is a key driver of MDS pathogenesis (Basiorka A, Blood 2016). Release of IL-1β by pyroptotic cells leads to paracrine stimulation of neighboring hematopoietic and stromal cells resulting in amplification of this circuit, myeloid derived suppressor cell (MDSC) accumulation as well as direct suppression of erythropoiesis. Thus, we investigated the combination of the IL-1β neutralizing antibody canakinumab in combination with darbepoetin in patients with ESA refractory lower risk MDS and present the final dose phase 1b data. Methods: Patients ≥ 18 years old with IPSS-R very low to intermediate risk MDS who were ESA refractory and hypomethylating agent (HMA) naïve with adequate organ function were eligible. Patients must have been RBC transfusion dependent or hemoglobin &amp;lt; 9 gm/dl with symptoms. Treatment consisted of subcutaneous (SC) canakinumab on day 1 of a 28 cycle (150mg dose level 1, 300mg dose level 2) and darbepoetin SC 300µg days 1 and 15 of each cycle for a total of 6 cycles with continuation of therapy for responding patients. The phase 1b portion utilized a 3+3 dose escalation design with 6 patients treated at the maximum tolerated dose (MTD) to define the recommended phase 2 dose (RP2D). Bone marrow (BM) disease assessments occurred every 3 cycles with response defined by IWG 2018 criteria. Quality of life was assessed by QUALMS (Abel A, Haematologica, 2016). Peripheral blood mononuclear cells (PBMCs) were obtained at disease assessments and day 15 of C1 for evaluation of adapter protein apoptosis associated speck-like protein containing a CARD (ASC) specks as a biomarker of inflammasome formation with quantification as previously described (McLemore A, Pyroptosis: Methods and Protocols, 2023). Total IL-1β of BM plasma was assayed by ELISA. Results: Nine patients enrolled with a median age of 71 (range: 61-85 years), 67% female with baseline IPSS-R, IPSS-M and mutation data shown in Table. By IPSS-M, 3, 3, 1, 2 patients were low, moderately-low, moderately high, and high-risk categories. All IPSS-M lower risk mutant patients had splicing mutations. The median number of mutations was 2 (range 0-5). 100% of patients were ESA refractory. Additionally, 33% and 56% were refractory to lenalidomide and luspatercept therapy, respectively. Eight (89%) patients were PRBC dependent at baseline (56% [n=5] with high transfusion burden). The median follow-up duration was 6.1 months (range 3-17.8). The most common adverse events were neutropenia (n=7), followed by thrombocytopenia (n=4), and abnormal liver function tests (n=4). There were two grade 3 adverse events including thrombocytopenia and colitis, both unrelated to study treatment. There were no dose-limiting toxicities or serious adverse events in the phase 1 portion. All patients achieved the best response as stable disease, and no one had progression disease. No patients achieved objective response or significant reduction in transfusion burden. There was no statistical improvement in total QUALMS score from baseline to end of treatment (P=0.72) nor in the individual components (i.e. physical burden, benefit finding and emotional burden, P=0.69, P=0.91, P=0.630; respectively) although several patients had individual improvements. The percentage of PBMCs with ASC specks at baseline ranged from 0.3945-2.978% (median 1.93%). ASC specks decreased significantly after cycle 1 of therapy and were durably suppressed over the course of treatment in a majority of patients (Figure). Extracellular IL-1β in bone marrow plasma robustly increased with treatment and remained elevated (representing non-functional IL-1β [canakinumab bound IL-1β]; P=0.002 cycle 6 versus baseline), supporting pharmacodynamic effect with no differences observed between DL1 and DL2. Conclusions: The combination of canakinumab and darbepoetin was safe and well tolerated and 300mg of canakinumab is the RP2D. Canakinumab inhibited inflammasome activation as evidenced by a reduction of ASC specks although this did not translate to clinical responses. Phase 2 of the study will focus on patients with lower transfusion burden and molecular subsets with highest IL-1β expression (e.g. TET2/ DNMT3A mutant).

Restoring natural upper limb movement through a wrist prosthetic module for partial hand amputees

BackgroundMost partial hand amputees experience limited wrist movement. The limited rotational wrist movement deteriorates natural upper limb system related to hand use and the usability of the prosthetic hand, which may cause secondary damage to the musculoskeletal system due to overuse of the upper limb affected by repetitive compensatory movement patterns. Nevertheless, partial hand prosthetics, in common, have only been proposed without rotational wrist movement because patients have various hand shapes, and a prosthetic hand should be attached to a narrow space.MethodsWe hypothesized that partial hand amputees, when using a prosthetic hand with a wrist rotation module, would achieve natural upper limb movement muscle synergy and motion analysis comparable to a control group. To validate the proposed prototype design with the wrist rotation module and verify our hypothesis, we compared a control group with partial hand amputees wearing hand prostheses, both with and without the wrist rotation module prototype. The study contained muscle synergy analysis through non-negative matrix factorization (NMF) using surface electromyography (sEMG) and motion analyses employing a motion capture system during the reach-to-grasp task. Additionally, we assessed the usability of the prototype design for partial hand amputees using the Jebsen-Taylor hand function test (JHFT).ResultsThe results showed that the number of muscle synergies identified through NMF remained consistent at 3 for both the control group and amputees using a hand prosthesis with a wrist rotation module. In the motion analysis, a statistically significant difference was observed between the control group and the prosthetic hand without the wrist rotation module, indicating the presence of compensatory movements when utilizing a prosthetic hand lacking this module. Furthermore, among the amputees, the JHFT demonstrated a greater improvement in total score when using the prosthetic hand equipped with a wrist rotation module compared to the prosthetic hand without this module.ConclusionIn conclusion, integrating a wrist rotation module in prosthetic hand designs for partial hand amputees restores natural upper limb movement patterns, reduces compensatory movements, and prevent the secondary musculoskeletal. This highlights the importance of this module in enhancing overall functionality and quality of life.

Patient-Reported Outcomes of Surgically Treated Lisfranc Injuries with Isolated Longitudinal Instability

Category: Midfoot/Forefoot; Other Introduction/Purpose: A longitudinal Lisfranc variant injury occurs from a longitudinal force on the midfoot directed through the first ray and medial cuneiform. This is unique in that other Lisfranc injury patterns typically result from an axial-directed force or a rotational force that externally rotates the midfoot. More common Lisfranc injury patterns can have instability longitudinally, but usually it is accompanied by coronal instability and even axial instability. To date, there has been no study with a cohort of Lisfranc injuries with isolated longitudinal instability. The purpose of this study was to report patient-reported outcome measures (PROMs) for those undergoing surgical treatment for longitudinal Lisfranc injuries. Methods: Retrospective chart review was completed to identify patients with surgically treated longitudinal Lisfranc injuries by a single surgeon between April 2018 and February 2022. Intraoperative fluoroscopy was used to confirm Lisfranc injuries positive for only longitudinal instability and negative for coronal and axial instability. Surgical technique consisted of open reduction internal fixation (ORIF) with a compression screw from the medial to middle cuneiform and a “homerun” compression screw from the medial cuneiform to the base of the second metatarsal. PROMs, collected preoperatively and postoperatively, included the Foot and Ankle Ability Measure (FAAM), Veterans RAND 12-Item Health Survey (VR-12), and visual analog scale (VAS) pain scale. Patient satisfaction was assessed through a survey consisting of a 0-100 rating scale with “least satisfied” being 0 and “most satisfied” being 100. Statistical analyses to determine significance were completed through sample t-tests assuming unequal variance with significance set at P&lt;.05. Results: Fourteen patients (14 feet) with an average age of 25.2±15.7 years sustained longitudinal Lisfranc injuries. Eleven of 14 patients competed in competitive sports when injured with football (n=5) being the most prevalent sport. Eleven patients underwent hardware removal an average of 3.6 months following their primary surgery. There were three cases of broken hardware, and one revision in which ORIF was converted to fusion. The average latest follow-up time for PROMs were 25.9 (range, 12-44) months. Results demonstrate a significant improvement in FAAM Total, FAAM ADL, and FAAM Sports scores at latest follow-up (Figure 1). There was also improvement in VR-12 Mental, VR-12 Physical, and VAS scores, though not statistically significant. Mean patient satisfaction at latest follow-up was 99/100. Conclusion: This study is the first to present data from a cohort of isolated longitudinal Lisfranc injuries. There is significant debate about surgical management of Lisfranc injuries. The improvement in PROMs at latest follow-up and high patient satisfaction suggests that ORIF may be an optimal surgical approach for management of longitudinal Lisfranc injuries.

Effect of ayurvedic interventions in the management of allergic rhinitis - An open label multi-centre single arm clinical study

Abstract BACKGROUND: The symptoms of Allergic Rhinitis,resemble the clinical presentation of Vataja Pratishyaya, a type of Pratishyaya, narrated in the Ayurveda classical texts. An exploratory clinical study was planned to assess the the safety and potential effect of a combination therapy of Ayurveda interventions, viz., Ayush VPR (a coded Ayurvedic formulation), Shirishadi Kwath (Anubhoota Yoga), and Nasya (intranasal drug administration) with Anutaila. MATERIALS AND METHODS: The study was an open-label, multicenter, prospective clinical study with pre-test and post-test design. Sixty participants aged between 18 and 65 years with the symptoms of AR were enrolled in the study as per the inclusion and exclusion criteria. The interventions given to the participants were Ayush VPR (3.5 g) powder, twice a day with honey and ghee after food, Shirishadi Kwath (20 ml) twice a day, orally on an empty stomach, and Anutaila Nasya (intranasal drug administration) for 7 days for two consecutive cycles with an interval of 7 days. The participants were assessed weekly for a total duration of 28 days. This was followed by a 28-day follow-up period, with assessments conducted at intervals of 14 days. The primary outcome was change in the CARAT (Control of Allergic Rhinitis and Asthma Test) score. RESULTS: Data of 60 participants were used for analysis. The mean age of participants was 35.8 ± 12.12., and the proportion of males and females were comparable with 51.7% females among the total participants. The mean CARAT score improved from baseline to the subsequent follow-ups at 7th, 14th, 21st, and 28th days. A significant improvement in the mean total CARAT score (P &lt; 0.001) was observed after the 28th day of treatment and also at the end of the 56th day in comparison to baseline. CONCLUSION: The Ayurvedic formulations, Shirishadi Kwath, Ayush VPR, and Anutaila, are safe and significantly reduce rhinorrhea, nasal itching, sneezing fits, nasal congestion, and nasal obstruction. The present study reveals that the Ayurvedic treatment provided highly significant relief from AR.

A clinical study to evaluate the efficacy of Ayurvedic interventions in the management of Pinasa (chronic rhinosinusitis)

Abstract BACKGROUND: The disease “Pinasa” is a chronic nasal disease affecting the nasal canal and paranasal sinuses and can be correlated with chronic rhinosinusitis in contemporary science. Given the literary indication, the present work evaluated the clinical efficacy and safety of Chitrak Haritaki Avaleha (CHA) and Shadbindu Taila (SBT) in the management of chronic rhinosinusitis. MATERIALS AND METHODS: This study was conducted as an open-label, multi-centre, prospective clinical study and executed at two institutes of the Central Council for Research in Ayurvedic Sciences at New Delhi and Patiala. In total, 120 participants aged between 18 and 60 years, suffering from chronic rhinosinusitis, were enrolled in the study. The interventions were Chitraka Haritaki (CHA) (06 g) in the form of Avaleha twice a day after food and Nasya with Shadbindu Taila (SBT) in the dose of 06 Bindu (drops) for 7 days for three consecutive cycles with intervals of 7 days. The participants were assessed every 14 days. The total duration of treatment was 42 days, followed by a follow-up of 28 days. The primary outcome was assessed as the change in the Rhino Sinusitis Disability Index (RSDI) score, and the secondary outcomes were change in the Sino Nasal Outcome Score (SNOT) 20 score and change in Lund–Mackay scores of CT scan para nasal sinus. RESULTS: A total of 120 participants were enrolled in the study (60 in each center). Among them, data of 115 participants who completed the study were used for analysis. The mean RSDI and SNOT 20 scores were observed to undergo gradual reduction from baseline to the 14th, 28th, and 42nd days. A significant improvement in the mean total RSDI score and SNOT 20 (P &lt; 0.001) was observed after the 42nd day of treatment and also at the end of the 70th day in comparison to baseline (# Compared using paired sample t-test). CONCLUSION: The Ayurvedic formulations, SBT Nasya and CHA administration, are safe and significantly reduce the symptoms such as Mucopurulent drainage (anterior, posterior, or both), nasal obstruction (congestion), facial pain-pressure-fullness, and decreased sense of smell.

Usefulness of mirtazapine and SSRIs in late-life depression: post hoc analysis of the GUNDAM study.

Mirtazapine and SSRIs are widely prescribed as first-line agents for late-life depression. However, evidence for these drugs is mostly based on non-elderly patients. Therefore, we reanalyzed a randomized controlled trial of mirtazapine versus SSRIs for depression in a sub-population of late-life patients. A randomized controlled trial was conducted with 141 patients, of whom 41 were elderly, and 100 were non-elderly. This study compared SSRIs and mirtazapine in late-life depression, examined late-onset and early adult-onset separately and compared elderly and non-elderly patients for each drug. Treatment effects and adverse events were assessed using the Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, respectively. In late-life depression, mirtazapine showed faster HAM-D total score improvement (3.3 points difference, p = 0.021) and higher improvement in insomnia (1.7 points difference, p = 0.001) and appetite (1.2 points difference, p = 0.020). Similar findings were observed for late-onset depression with the HAM-D total score (4.3 points difference, p = 0.007) and appetite (0.9 points difference, p = 0.004), favoring mirtazapine. Depressive symptoms were generally less improved in late-life depression than in non-late-life depression. Regarding the effect of mirtazapine on appetite, late-life depression showed greater improvement (0.7 points difference, p = 0.008). Nausea and micturition disturbances were more common with SSRIs in late-life depression than in non-late-life depression. In contrast, somnolence was less common in late-life depression with mirtazapine. The potential usefulness of mirtazapine in elderly patients was demonstrated. The results also showed differences in the treatment response to SSRIs and mirtazapine between elderly and non-elderly patients.

The Effect of Radiofrequency Therapy on Sexual Function in Female Cancer Survivors (Gynecologic and Breast) and Non-cancer Menopausal Women: A Single-Arm Trial.

Introduction: Up to 90% of postmenopausal women and female cancer survivors may be affected by the genitourinary syndrome of menopause (GSM), with a negative impact on sexual function and quality of life. A novel energy-based device among the treatment options for GSM is radiofrequency therapy (RFT). RFT is a treatment option that uses energy from radio waves to heat the tissue. The objective of this study was to assess the impact of RFT on sexual function in female cancer survivors (gynecologic and breast) and non-cancer menopausal women. Methods: In a single-arm prospective trial, the efficacy of RFT in both female cancer survivors (gynecologic and breast) and non-cancer menopausal women with sexual dysfunction at a tertiary and referral center (Imam Hossein Medical Center, Tehran, Iran) was evaluated between April 2022 and December 2022. The study protocol consisted of 3 monthly RFT sessions. Examination was performed at baseline (T0) and 3 months after the last RFT session (T1). The primary outcome was sexual function, which was assessed using the Female Sexual Function Index (FSFI). In addition, adverse events were evaluated during treatment and at T1. Results: A total of 37 female cancer survivors (mean [SD] age: 49.4 [8.9] years) and 37 non-cancer menopausal women (mean [SD] age: 53.8 [5.5] years) were enrolled. Patients exposed to RFT showed a significant improvement in FSFI scores when compared to baseline scores for both female cancer survivors (13.07, 95% CI: 12.27 - 13.86) and non-cancer menopausal women (13.18, 95% CI: 12.34 - 14.03). There was no difference in FSFI total score improvement between the two groups (t(72)=0.06, P=0.951). There were no serious adverse events associated with RFT. Conclusion: The efficacy of RFT as a treatment for sexual dysfunction has been demonstrated in both non-cancer menopausal women and female cancer survivors. In both groups, a significant improvement was confirmed.

Predictors of treatment response to pregabalin in unexplained or refractory chronic cough

BackgroundPatients with chronic cough (>8 weeks) often remain symptomatic after appropriate investigations and therapeutic trials. Prior research has shown a benefit in certain individuals from pregabalin, but clinical improvement is quite unpredictable and variable. ObjectiveThe main objective of this study was to identify the demographic and clinical characteristics associated with a higher likelihood of cough improvement with a trial of pregabalin therapy. Methods50 consecutive patients with chronic cough were enrolled in this prospective cohort study. Subjects were prescribed pregabalin 75 mg oral qhs for 4 weeks followed by 75 mg oral bid. Leicester Cough Questionnaire (LCQ) was completed at treatment initiation and after 3 months of therapy. A comparison was performed between treatment responders (LCQ total score improvement ≥1.3) and non-responders. Results56% of patients reported a LCQ total score improvement ≥1.3 (minimal clinically important difference). Responders to pregabalin therapy were more likely to have refractory (with underlying pulmonary disease) versus unexplained chronic cough (p = 0.01). Patients with significant improvement were also on average more symptomatic at baseline (mean LCQ total score 10.2 versus 13.0, p < 0.01). No significant relationship was identified with age, gender, body mass index, history of anxiety and/or depression, cigarette smoking history, or cough duration (p > 0.05). The unexplained chronic cough group had a strong female predominance (85.7% versus 40.9% for refractory cough, p < 0.01). ConclusionThis is the first study that has investigated clinical predictors of treatment response to pregabalin in chronic cough patients. Further research is needed to develop therapies for subjects who do not improve with currently available neuromodulating medications.

Efficacy and safety of aclidinium/formoterol versus monotherapies and aclidinium versus placebo in Chinese and other Asian patients with moderate-to-severe COPD: The AVANT Phase 3 study

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 μg/12 μg combination vs monotherapies and aclidinium vs placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease. Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV1) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124 mL; p < 0.001), and in trough FEV1 vs formoterol (LS mean 85 mL; 95% CI 53, 117 mL; p < 0.001). Furthermore, aclidinium provided improvements in trough FEV1 vs placebo (LS mean 134 mL; 95% CI 103, 166 mL; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not for aclidinium vs placebo (LS mean 0.4; 95% CI −0.1, 1.0; p = 0.132). Improvements in St George's Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean −4.0; 95% CI −6.7, −1.4; p = 0.003) and aclidinium vs placebo (LS mean −2.9; 95% CI −5.5, −0.3; p = 0.031). Aclidinium/formoterol and aclidinium were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively), and AEs leading to discontinuation of study medication (2.3, 1.5, and 2.2%, respectively) were similar between groups.