Single-arm Study Research Articles

Double intrastromal corneal ring segment implantation: a new approach for improved clinical outcomes in keratoconus patients

AIM: To evaluate the clinical outcomes after subsequent implantation of a new intrastromal corneal ring segment (ICRS) model followed by an additional short-arc ICRS implant in keratoconus patients. METHODS: This retrospective single-arm cohort study evaluated 25 eyes of 21 keratoconus patients implanted with the new ICRS followed by 140-arch length ICRS (140-ICRS) implantation. Uncorrected distance visual acuity (UDVA, logMAR), corrected distance visual acuity (CDVA, logMAR), sphere, astigmatism, keratometry, spherical equivalent (SE), and asphericity were compared preoperatively and postoperatively after both ICRS implantation. RESULTS: The average follow-up time after 140-ICRS implantation was 6.40±2.20mo. The mean preoperative UDVA improved from 1.27±0.14 preoperative to 0.52±0.26 after both ICRS implantation (P=0.03). The mean sphere value reduced from -5.34±2.74 preoperatively to -2.06±1.84 postoperatively (P<0.001) after the first ICRS implantation and decreased to -0.59±1.54 postoperatively (P<0.001) after 140-ICRS implantation. The mean preoperative astigmatism was -3.72±1.56 and improved to -2.82±1.08 after the first ICRS implantation, and following the 140-ICRS implantation, the mean astigmatism was -1.37±0.67 (P=0.001). The SE and asphericity changes were statistically significant (P<0.001). The researchers did not find intraoperative or postoperative complications for both procedures. CONCLUSION: The combination of 2 different ICRSs can efficiently regularize the cornea, reduce the SE, and improve visual acuity in selected keratoconus patients.

Digital Health Platform for Improving the Effect of the Active Health Management of Chronic Diseases in the Community: Mixed Methods Exploratory Study

Background China is vigorously promoting the health management of chronic diseases and exploring digital active health management. However, as most medical information systems in China have been built separately, there is poor sharing of medical information. It is difficult to achieve interconnectivity among community residents’ self-testing information, community health care information, and hospital health information, and digital chronic disease management has not been widely applied in China. Objective This study aimed to build a digital health platform and improve the effectiveness of full-cycle management for community chronic diseases through digital active health management. Methods This was a single-arm pre-post intervention study involving the development and use of a digital health platform (2-year intervention; 2020 to 2022). The digital health platform included the “i Active Health” applet for residents and the active health information system (cardio-cerebrovascular disease risk management system) for medical teams. The digital active health management of chronic diseases involved creating health streets, providing internet-assisted full-cycle active health services for residents, implementing internet-based community management for hypertension and diabetes, and performing real-time quantitative assessment and hierarchical management of residents’ risks of cardio-cerebrovascular disease. After the 2-year intervention, management effectiveness was evaluated. Results We constructed a digital health platform with interconnected health information and implemented a digital active health management model. After the intervention, the 2-way referral between community health care institutions and hospitals increased. Residents’ health literacy rate increased from 30.6% (3062/10,000) in 2020 to 49.9% (4992/10,000) in 2022, with improvements in health knowledge, health behavior, and health skills. Moreover, the risk of cardio-cerebrovascular disease decreased after the intervention. The community hypertension and diabetes standardized management rates increased from 59.6% (2124/3566) and 55.8% (670/1200) in 2020 to 75.0% (3212/4285) and 69.4% (1686/2430) in 2022, respectively. The control rates of blood pressure in patients with hypertension and blood sugar in patients with diabetes increased from 51.7% (1081/2091) and 42.0% (373/888) in 2020 to 81.2% (1698/2091) and 73.0% (648/888) in 2022, respectively. The intervention improved patients’ BMI, waist circumference, blood uric acid levels, and low-density lipoprotein cholesterol levels. The drug compliance rate of patients with hypertension and diabetes increased from 33.6% (703/2091) and 36.0% (320/888) in 2020 to 73.3% (1532/2091) and 75.8% (673/888) in 2022, respectively. The intervention greatly improved the diet behavior, exercise behavior, and drinking behavior of patients with hypertension and diabetes. Conclusions Our digital health platform can effectively achieve the interconnection and exchange of different health information. The digital active health management carried out with the assistance of this platform improved the effectiveness of community chronic disease management. Thus, the platform is worth promoting and applying in practice.

Training of Nurse Interventionists to Optimize Intervention Fidelity in a Telehealth Pilot Study.

Interventionist training and on-going guidance by the research team are essential in psychosocial interventional research to ensure fidelity. Consistency in delivering an intervention requires recruiting interventionists with well-aligned clinical experience, developing a replicable training process, and reassessing ongoing intervention fidelity using an assessment tool of observable behaviors that are essential to the intervention. This paper describes one research team's experience of hiring and training nurse interventionists to deliver a theory-based, telehealth psychosocial intervention for a single-arm pilot study. The training methods used to foster the nurses' integration of theory into intervention delivery are discussed, along with approaches adopted to optimize and measure fidelity. The research team and interventionist trainees in this pilot study overcame learning challenges through establishing mutual trust and promoting effective communication throughout the training process. Fostering connections between cognitive and affective learning during the nurse interventionists' training was critical to establishing and maintaining intervention fidelity.

Feasibility study of the e-learning version of the "Journey of the Brave:" a universal anxiety-prevention program based on cognitive behavioral therapy.

School-based cognitive behavioral therapy (CBT) programs could contribute toward preventing anxiety disorders in children. However, setting aside class time for such programs is difficult. Internet-based CBT (I-CBT) is an efficient way to provide CBT. However, studies on I-CBT for anxiety prevention remain scarce, including I-CBT for school-based universal prevention programs. Therefore, we developed an e-learning version of a school-based anxiety-prevention CBT program, "Journey of the Brave," which was effective in Japan, to make it more flexible and accessible. This study evaluated its feasibility. We conducted a single-arm study based on 44 parents and children. Children aged 10-12years took the e-learning program at home. Parents and children responded to a questionnaire three times: before the learning (Pre), after the learning (Post), and three months later (FU: Follow-up). Feasibility was comprehensively evaluated through dropout rates, satisfaction and learning records, and changes in scores on psychological scales assessing anxiety symptoms, emotion-regulation skills, and children's emotional and behavioral problems. Of the 44 children, 42 started the e-learning, and 32 continued it (dropout rate of 23.8%). Furthermore, 83.9% of the children and 96.8% of the parents responded "agree" or "somewhat agree" regarding overall satisfaction. The parent-rated Spence Children's Anxiety Scale(SCAS) (SCAS-P) showed a significant decrease between Pre and FU (p = 0.014, 95% CI = (-9.22, -0.84)); however, the child-rated SCAS (SCAS-C) reduction was not significant (p = 0.08). The Emotion‑Regulation Skills Questionnaire (ERSQ) also increased significantly between Pre and FU (p = 0.045, 95% CI = (0.18, 18.31)). The Total Difficulties Score of the Strengths and Difficulties Questionnaire(SDQ) decreased significantly from Pre to Post (p = 0.025, 95% CI = (-3.62, -0.19)); however, it was not significantly different between Pre and FU (p = 0.67). The e-learning version showed low dropout rates and high satisfaction ratings from parents and children. Moreover, this study did not rule out the possibility that the program reduced children's anxiety and improved their emotional-regulation skills. Therefore, its potential and feasibility were indicated. UMIN, UMIN000049182, Registered 11 October 2022.

Efficacy and safety of safinamide in Parkinson's disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with≥1.5 h of "off" time daily, who took levodopa≥3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily "off" time (-1.3±2.4 h, p<0.001) and quality of life (QoL) based on PDQ-39 summary index (-2.7±10.3, p<0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily "on" time without dyskinesia (all p<0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.

Three-Year Clinical and Hemodynamic Evaluation of the Hydra Self-Expanding Transcatheter Aortic Valve in Patients With Severe Aortic Stenosis.

The Hydra CE study revealed 1-year favorable efficacy of TAVR, showing a large effective orifice area (EOA), low gradient, and acceptable complication rates. We evaluated the 3-year clinical and hemodynamic outcomes of Hydra self-expanding transcatheter aortic valve (manufactured by Vascular Innovations Co Ltd, Nonthaburi, Thailand; a subsidiary of Sahajanand Medical Technologies Limited, India) in patients with symptomatic severe aortic stenosis at high or extremely high surgical risk. The Hydra CE study was a prospective, multicenter, single-arm study. A total of 157 patients were enrolled in the study, out of whom 54 patients from two centers (Lithuania and Poland) had provided consent for long-term follow-up at recruitment, with a planned 5-year follow-up period. The primary endpoint was all-cause mortality, and patients were followed up for up to 3 years, with an assessment of clinical and echocardiographic outcomes. Among the 54 patients, the average age was 81.0 ± 4.1 years. The mean STS score was 3.2 ± 2.0%. At 3 years, all-cause mortality had occurred in 14.8% of patients, including 3.7% cardiovascular deaths and 1.9% device-related deaths. There was a progressive enhancement in EOA that is, 0.68 ± 0.15 cm2 at baseline to 1.97 ± 0.52 cm2 at 3 years (p < 0.001) as well as significant improvement in the mean aortic valve gradient that is, 53.4 ± 14.24 mmHg at baseline to 8.6 ± 2.80 mmHg at 3 years (p < 0.001). New permanent pacemaker implantation rates up to 3-year follow-up was 12.9%. The 3-year results of the Hydra CE study demonstrated consistent improvements in hemodynamics over time. The study also revealed favorable safety and efficacy trends, along with low occurrences of new permanent pacemaker implantations and paravalvular leaks.

“Optimizing Wellness and Neurorehabilitation with Mindfulness (OWNMindfulness)”: feasibility of a novel mindfulness-based rehabilitation intervention for Persisting Symptoms after Concussion

Background Persisting Symptoms after Concussion (PSaC) are common and difficult to treat. Mindfulness-based interventions can support recovery but are rarely included in rehabilitative care. We developed OWNMindfulness, an eight-week live-video mindfulness-based group for PSaC. Purpose To assess feasibility and preliminary clinical effects of OWNMindfulness. Methods Fourteen individuals with PSaC enrolled in this mixed-methods single-arm feasibility study. We assessed enrollment/retention, adherence, fidelity, instrument completion, safety, and satisfaction. We evaluated preliminary trends in the impact of the intervention on mindfulness (CAMS-R), concussion symptoms (PCSS), and QOL (WHOQOL-BREF). Qualitative analysis of exit interviews explored participants’ perceptions of the effects of the intervention, and framework analysis assessed adequacy of the quantitative measures to capture perceived effects. Results Feasibility results met a priori benchmarks. Mindfulness, concussion symptoms, and QOL scores improved (CAMS-R: adjusted p = 0.01, large effect size; PCSS: adjusted p = 0.03, moderate effect size; WHOQOL-BREF: not significant, small effect size). Qualitative analysis of interview data found benefits including validation, compassion, self-awareness, self-efficacy, concussion symptoms, resilience, life participation, social relationships, and QOL. Framework analysis demonstrated that quantitative tools captured change in concussion symptoms but did not comprehensively assess the other benefits identified through qualitative methods. Conclusions OWNMindfulness shows preliminary feasibility and promise for improving clinical outcomes. Results suggest the need for additional quantitative tools for comprehensive measurement of the effects and may point to potential mechanisms of action.

CTNI-24. WF-1801: SINGLE ARM PILOT STUDY OF RAMIPRIL FOR PREVENTION OF RADIATION-INDUCED COGNITIVE DECLINE IN GLIOBLASTOMA PATIENTS RECEIVING CHEMORADIOTHERAPY

Abstract BACKGROUND Patients with glioblastoma (GBM) experience cognitive decline after chemoradiation. Radiation therapy (RT) to the brain creates chronic inflammation believed to contribute to cognitive decline. Ramipril counteracts neuroinflammatory changes in pre-clinical models when given during RT. METHODS This prospective single arm study (WF-1801) coordinated by the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base assessed feasibility, tolerability, and potential efficacy of using ramipril in patients with GBM. Eligibility and treatment paradigms mirrored NRG/RTOG 0825 allowing for outcomes from the placebo arm to be used for comparison. Participants took ramipril during 6 weeks of chemoradiation with temozolomide and for 3 months after RT. Patients completed cognitive testing (HVLT-R, TMT, and COWA) and patient-reported outcomes at baseline, RT completion, and 1 and 4 months after RT. Co-primary endpoints were retention rate (compliance with 75% doses and completion of cognitive testing) and change in cognitive composite score 1 month after RT. RESULTS 75 participants were accrued between 3/25/2019 and 11/14/23: 65% were male, 89% White, median age 63 years. The NRG/RTOG 0825 placebo cohort (n=247) was younger (median 57, p&amp;lt;0.0001) with more White participants (95%, p=0.04). The overall retention rate in WF-1801 was 48% (one-sided 95% CI: 38%-100%); 61% completed &amp;gt;=75% of doses; 57% completed cognitive testing at all time points. The median (range) change in cognitive composite score 1 month after RT was 0.01 (-82.6, 13.0) reflecting an improvement from baseline. However, this was not significantly different from the NRG/RTOG 0825 placebo group median of 0.10 (-48.2, 8.6); p=0.49. CONCLUSION The overall retention rate fell short of our pre-specified endpoint of &amp;gt; 65%; however, medication compliance was high and well-tolerated in retained patients. Future investigations could identify patient subsets who may benefit more from concurrent ramipril. WF-1801 (NCT03475186) funded by UG1CA189824. NRG/RTOG-0825 (NCT00884741) funded by U10CA180868 and U10CA021661.

Safety of a Novel Continuous Glucose Monitoring–Informed Insulin Bolus Calculator Mobile Application for People With Type 1 or Type 2 Diabetes

BACKGROUND Managing bolus insulin dosing can be a significant burden for people with diabetes, many of whom have limited numeracy skills. Insulin bolus calculators (IBCs) may improve glycemia as well as treatment satisfaction. OBJECTIVE The purpose of this study was to demonstrate the safety of a novel, continuous glucose monitoring (CGM)-informed IBC mobile device app that applies trend arrow adjustments to bolus insulin dose recommendations. RESEARCH DESIGN AND METHODS This clinical trial was an open-label, industry-sponsored single-arm study conducted at two sites. Fifty-four participants with type 1 or type 2 diabetes were enrolled and used the IBC app on their mobile device for 30 days. Study participants were adults who were already using CGM and dosing bolus insulin. The analysis examined both noninferiority and superiority of time in range (TIR) during the study period compared with baseline. Other important end points included hypoglycemia, glucose variability, nocturnal and diurnal TIR, and diabetes distress. The per-protocol (PP) group was defined as participants who used the IBC &amp;gt;30 times during the study. RESULTS Mean TIR improved by 3.8% (95% CI 0.7–6.9%) from 69.2 to 73.0% (P = 0.017) in the PP group. This TIR corresponds to a mean of 0.9 more hours per day spent in range, and the improvement was driven by those with type 2 diabetes. There was no increase in measures of hypoglycemia or diabetes distress. Exploratory analysis revealed a reduction in measures of glucose variability. In addition, individuals with type 1 diabetes had greater improvements in diurnal TIR than in nocturnal TIR. CONCLUSION A CGM-informed IBC app that applies trend arrow adjustments to bolus insulin dose recommendations improved TIR without increasing hypoglycemia or diabetes distress in individuals with type 1 or type 2 diabetes.

CTIM-33. IMMUNE BIOMARKERS OF TREATMENT RELATED IMAGING CHANGES IN GLIOBLASTOMA PATIENTS TREATED WITH STANDARD OF CARE PLUS PEMBROLIZUMAB

Abstract Pseudoprogression is a post-treatment imaging phenomenon in glioblastoma (GBM) that mimics true progression. Immune checkpoint inhibition with pembrolizumab has shown clinical benefits in multiple cancers and is a burgeoning treatment in GBM. Discerning pseudoprogression, or treatment-related imaging changes, from true progression is essential for appropriate treatment recommendations. However, there are no reliable biomarkers that can differentiate between pseudoprogression and true progression. Our prospective single-arm study (NCT 03347617) evaluated immune cell sub-populations (B-cells, T-cells, NK cells, monocytes, and myeloid cells) in newly diagnosed GBM patients who received standard-of-care chemoradiation plus concurrent pembrolizumab after maximal safe resection. Flow cytometry was performed on blood collected at predetermined timepoints (pre-treatment, post-radiation, suspected progression, and confirmed progression) and immune cell sub-populations were evaluated as covariates in univariable and multivariable logistic regression analysis. Of the 56 patients enrolled in this trial, 51 completed blood collection. Median survival was 13.84 months. Fifteen (29%) patients had pseudoprogression by modified RANO criteria and 36 (70.5%) had suspected or confirmed progression. Univariable analysis identified the following serum derived immune populations as being significantly associated with pseudoprogression: cytotoxic T-cell percentage (CD3+CD8+; HR: 1.10; p=0.045); total NK Cells percentage (CD3+CD56+; HR:0.912; p=0.0.053); IGD+CD27-naïve B-cells of B-cell percentage (HR: 0.976; p=0.014); IGD+CD27+non-switched B of B-cell percentage (HR:1.07; p=0.036). Backward selection multivariable logistic regression analysis confirmed the significant association of cytotoxic T-cell percentage (CD3+CD8+; HR:1.02; p=0.049) with pseudoprogression while controlling for IGD+CD27+non-switched B of B-cell percentage (HR:1.01, p=0.116). Increasing levels of serum cytotoxic T-cells in GBM patients treated with standard-of-care plus pembrolizumab is associated with pseudoprogression and may be used to differentiate between true progression. Validation of results is needed in a control population treated with standard-of-care prior to clinical implementation. Future studies will utilize serum immune biomarkers coupled with radiomic features to better characterize the pseudoprogression signature in GBM.

QOL-17. REFLECTIONS ON A PSYCHOEDUCATION INTERVENTION FOR PATIENTS WITH NEWLY DIAGNOSED BRAIN TUMORS (NEUROPATHWAYS): A QUALITATIVE STUDY

Abstract BACKGROUND Patients with newly diagnosed primary malignant brain tumors (PMBT) face unique challenges processing and absorbing information regarding their diagnosis, often while contending with cognitive and communication deficits. Limited research exists regarding optimal information provision and support for this highly distressed population. We used input from clinician, patient, and caregiver stakeholders to design a population-specific, psychoeducation intervention (“NeuroPathways”) to address these needs. METHODS We conducted a single-arm study (N=12) to pilot and refine NeuroPathways in English-speaking patients within six-weeks of a PMBT diagnosis. Neuropathways comprises 1) a comprehensive (105 pages) handbook covering information about PMBT diagnosis, treatment, coping, self-care, and vetted resources, and 2) four brief, individual telehealth sessions with a trained interventionist (e.g., psychologist, physician) over 4-8 weeks to assist and empower patients to obtain information, support, and coping guidance at their preferred depth and pace, using the handbook as a resource. Ten participants completed all four sessions and participated in semi-structured exit interviews. We used rapid qualitative analysis to explore participants’ perceptions of intervention delivery, content, and benefit. RESULTS Participants (83% male, median age=52 years) uniformly described NeuroPathways as accessible, citing the telehealth format as particularly important for facilitating participation given logistical challenges related to cancer treatment. Perceived benefits of participation included: a) access to well-organized information targeting both current and future disease- and treatment-related concerns; b) increased skill in problem solving and communication with loved ones and/or medical providers; c) personalized emotional support from interventionists. While most felt the timing was appropriate, several who enrolled later in the eligibility window stated a desire for earlier intervention. CONCLUSION Participant feedback highlights the accessibility and potential benefits of this psychoeducation intervention for patients with newly diagnosed PMBT. These data will inform refinement of NeuroPathways in preparation for a pilot randomized controlled trial to formally assess feasibility and acceptability.

CTNI-42. A BIOMARKER-GUIDED PHASE 2 STUDY OF DB107-RRV (A RETROVIRAL REPLICATING VECTOR) COMBINED WITH DB107-FC (FLUCYTOSINE EXTENDED-RELEASE TABLETS) IN PATIENTS WITH RECURRENT GLIOBLASTOMA OR ANAPLASTIC ASTROCYTOMA: A CLINICAL PROTOCOL

Abstract INTRODUCTION Despite significant advances in understanding the basic pathogenesis of glioblastoma, the median survival of patients has minimally changed in the past 25 years with a 5-year survival rate of &amp;lt;7%. Because of the dismal prognosis, attention has shifted to alternative adjuvant treatment modalities including gene/viral-based therapy. The first clinically tested replicating retroviral vector DB107-RRV (vocimagene amiretrorepvec, formerly Toca511) was assessed in a randomized Phase 3 study (NCT02414165) to evaluate the intracranial administration of DB107-RRV with subsequent oral administration of DB107-FC (5-fluocytosine extended-release tablets) in patients with recurrent HGG. Although the primary endpoint of overall survival (OS) in the intent-to-treat population was not met (median OS=11.07 months, DB107-RRV+ DB107-FC arm and 12.22 months for the SOC arm (HR=1.06; 95% CI:[0.83, 1.35], p=0.6154)), post-hoc analysis identified a subgroup of patients (responders) who demonstrated a marked survival benefit from the Phase III clinical trial (Toca 5, NCT02414165). Using a non-invasive genotyping pipeline, a novel biomarker, DGM7, was identified among responders that confers an improved prognosis: (DB107-RRV+DB107-FC is 18.3 months vs. 12.0 months in the SOC group (HR=0.50; 95% CI:[0.28, 0.89], p= 0.0167)). DGM7 is present in the blood of approximately 20-30% of HGG patients. METHODS This is a Phase 2, single-site, open-label, single-arm study to assess the oral administration of DB107-FC in combination with DB107-RRV in DGM7+ patients with recurrent/progressive HGG. Key inclusion criteria include presence of the DGM7 biomarker in blood, patient age 18–75 with histologically proven, measurable (MRI) recurrent/progressive HGG, and no radiation therapy for at least 12 weeks without histopathologic/MRI progression confirmation. The primary endpoint of this study will be progression-free survival at 6 months (PFS6) and OS of DB107-RRV+DB107-FC in DGM7+ patients with recurrent/progressive HGG compared to the historical study arm SOC/DGM7+ from NCT02414165.

Pilot evaluation on an adapted tele-behavioral activation to increase physical activity in persons with depression: a single-arm pilot study

BackgroundPhysical activity has the potential to improve physical and mental health outcomes of persons with depression. However, feasible and acceptable strategies to integrate physical activity interventions into real-world settings are needed.ObjectiveTo assess the feasibility and acceptability of a manualized Behavioral Activation intervention aimed to increase physical activity in persons with depression (defined as a PHQ-9 score ≥ 10).MethodsA single-arm pilot study was conducted. The intervention consisted of 8 tele-therapy sessions delivered over a 10-week period. Measures of feasibility included screening, enrollment, intervention adherence, outcome data availability, and intervention fidelity. Acceptability was assessed with a post-intervention survey and qualitatively through focus groups and interviews. Preliminary efficacy of the intervention was assessed by evaluating pre-to-post changes in physical activity and depressive symptoms.ResultsAll feasibility metrics exceeded predetermined feasibility goal metrics with the exception of Fitbit wear and screening rate, which was due to a greater than anticipated enrollment rate. Participants (n = 15) reported perceived benefits from the intervention and convenience in attending tele-therapy sessions. Depressive symptoms, as measured by the PHQ-9 improved (16.8 at enrollment to 10.1 post intervention, Cohen’s d = 1.13). Self-reported moderate-to-vigorous physical activity (MVPA) increased from 22.0 min/week at baseline to 36.67 min/week post-intervention (d = 0.58). Physical activity as measured by the Fitbit showed little change (daily step 5543.29 during Week 1 to 6177.48 during Week 10, (d = 0.14); MVPA 21.23 min/week during Week 1 to 19.22 at Week 10 (d = 0.0.06).ConclusionsResults of the pilot study suggest the intervention is feasible to deliver and acceptable to participants. Preliminary results suggest the intervention may be effective in improving depressive symptoms and increasing self-reported physical activity.Trial registrationClinicalTrials.gov NCT04990401, Registered July 21, 2021.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol

BackgroundFluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3–4 (≥ G3) toxicities that require hospital-based management ± intensive care admission. Approximately 1% of patients die secondary to FP toxicities. Prospective screening for DPYD gene variants (encoding the key enzyme for FP catabolism) can identify patients at risk of ≥ G3 toxicity and allow for dose adjustment prior to first FP exposure. Evidence supports this as a cost-effective method of improving patient safety and reducing healthcare burden internationally; however, no Australian data confirms its feasibility on a large scale.MethodThis investigator-led, single-arm study will determine large scale feasibility of prospective DPYD genotyping, confirming patient safety and cost-effectiveness within the Australian health care system. 5000 patients aged 18 years and older with solid organ cancers requiring FP chemotherapy will be consented and genotyped prior to commencing treatment, and early toxicity (within 60 days) post-FP exposure will be determined. Toxicity data for DPYD variant carriers who have dose adjustments will be compared to the wild-type cohort and historical cohorts of carriers who did not undergo genotyping prior to FP exposure, and prospective variant carriers who do not undergo dose-adjustment. Prevalence of the four standard DPYD gene variants will be confirmed in an Australian population. Additionally, health economic analysis, implementation research via semi-structured interviews of patients and clinicians, and feasibility of UGT1A1 genotyping will be conducted.DiscussionThis study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing.Trial registrationThis trial was registered with the Australian and New Zealand Cancer Trials Registry on 13th Dec 2023, ACTRN12623001301651.

Efficacy and Safety of Risankizumab in Patients with Psoriasis Showing Suboptimal Response to Secukinumab or Ixekizumab: Results from a Phase 3b, Open-Label, Single-Arm (aIMM) Study.

Risankizumab has demonstrated superior efficacy compared to other psoriasis treatments, including secukinumab, adalimumab, and ustekinumab; switching to risankizumab from other psoriasis treatments has shown superior clinical and quality of life (QoL) outcomes. We evaluated the efficacy and safety of directly switching patients with moderate-to-severe plaque psoriasis and a suboptimal response to interleukin (IL)-17 inhibitors (secukinumab or ixekizumab) to risankizumab. This 52-week, phase 3b study enrolled patients (≥ 18years) with moderate-to-severe plaque psoriasis who had previously been treated with the recommended dose of secukinumab or ixekizumab for ≥ 6months but did not achieve an optimal response (static Physician's Global Assessment [sPGA] 2/3; body surface are [BSA] 3- < 10%). Patients received subcutaneous risankizumab (150mg) without washout. The primary endpoint was the proportion of patients achieving sPGA of 0/1 at week 16. Secondary endpoints included sPGA 0/1 at week 52, sPGA 0, Dermatology Life Quality Index (DLQI) 0/1, and Psoriasis Symptoms Scale (PSS) 0 at weeks 16 and 52. Safety was monitored throughout the study. The study included 244 patients. sPGA 0/1 was achieved by 57.4% and 62.3% at week 16 and 52. At week 16, sPGA 0, DLQI 0/1, and PSS 0 were achieved by 20.5%, 40.2%, and 20.9%, respectively. At week 52, these proportions increased to 27.1% for sPGA 0, 47.2% for DLQI 0/1, and 27.5% for PSS 0. Most frequently reported adverse events (reported in ≥ 5% of patients) in risankizumab-treated patients were COVID-19 infection (8.6%) and nasopharyngitis (5.7%). No new safety signals were observed. Directly switching to risankizumab improved outcomes and QoL in patients with moderate-to-severe psoriasis who had suboptimal responses to anti-IL-17 inhibitors (secukinumab or ixekizumab). The safety results are consistent with previously reported safety of risankizumab. This study supports the efficacy of risankizumab in patients previously treated with biologics, including IL-17 inhibitors, and suggests a direct switch to risankizumab for improved clinical outcomes and QoL. ClinicalTrials.gov identifier: NCT04102007.

Phase 3 Open-Label Study Evaluating the Efficacy and Safety of Mavacamten in Japanese Adults With Obstructive Hypertrophic Cardiomyopathy - The HORIZON-HCM Study.

Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear. HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study. In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.

Aromatase inhibitors, bone microstructure, and estimated bone strength in postmenopausal women with breast cancer: a 5-year prospective study.

Aromatase inhibitors (AIs) are the standard treatment for early breast cancer (EBC) and are typical causative agents of cancer treatment-induced bone loss. However, the effects of long-term treatment with these drugs on bone microstructure remain unclear. This prospective, single-arm observational study included postmenopausal, non-osteoporotic women with hormone receptor-positive EBC. Patients who underwent dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type I N-terminal propeptide levels were compared at baseline and at 60months after commencing AI treatment. Fifteen women were included in the study, with a median age of 58years and a quartile range of 56.5-62.5years. At 60months, HR-pQCT revealed that the cortical area and thickness decreased with increased cortical porosity in the cortical bone. In addition, the number of trabeculae decreased and trabecular separation increased trabecular bones decreases, and trabecular bone separation opens, resulting in a decrease in the trabecular bone volume fraction. Total bone mineral density (BMD), trabecular volumetric BMD, and cortical volumetric BMD, and estimated bone strength significantly decreased. DXA BMD values significantly decreased in the total hip and femoral neck but not the lumbar spine. TRACP-5b values after 5years of AI treatment showed a significant negative correlation with the rate of change in the total volumetric BMD in the distal tibia. Postmenopausal women who received AIs for 5years for EBC experienced significant deterioration in the bone microstructure, BMD, and estimated bone strength.

Magnetic resonance imaging-guided single-fraction preoperative radiotherapy for early-stage breast cancer (the RICE trial): feasibility study

BackgroundOver the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer.MethodsThe RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac.The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI.ConclusionThe RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.

A phase 1/2 study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia.

This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia. In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2). In phase 1, MTD was not reached and RED was 120 mg/day. In phase 2, the CR rate was 50.0% after induction (90% confidence interval [CI] 40.4, 59.6); however, the lower confidence limit did not exceed the pre-defined 55% benchmark. Composite CR (CRc) rates were high following induction (86.6%, 95% CI [77.3, 93.1]), consolidation, and maintenance therapy (87.8%, 95% CI [78.7, 94.0], each). The probability of OS was 86.6% at 12 months. No new safety findings were reported. In this interim analysis, gilteritinib 120 mg/day in combination with chemotherapy was well tolerated, with similar CRc rates to previous studies.

Validation and efficacy of a tele-yoga intervention for improving psychological stress, mental health and sleep difficulties of stressed adults diagnosed with long COVID: a prospective, multi-center, open-label single-arm study

The objective of this study was to validate and test the efficacy of a 16-week tele-yoga intervention for perceived stress, anxiety, depression, and insomnia in individuals who had had COVID-19 infection in the previous year, and had reported moderately high levels of psychological stress (PSS ≥14). 25 and 50-min versions of the program were developed. They were then validated using Lawshe’s content validity ratio after obtaining feedback from 20 yoga therapy experts. The safety and efficacy of the two programs were subsequently tested in a prospective, multicenter, open-label single-arm study. Eighty-six adults (18 male, 68 female) were recruited from two tertiary mental healthcare institutions, 48 in NIMHANS, Bengaluru; and 38 in SCARF, Chennai. Participants were assessed at weeks zero, 4, and 16 using validated tools. Data were analyzed using a Mixed Model, Intention to Treat approach. After week 16, 31 subjects remained in the trial and continued to practice yoga without any side effects. Subjects who adhered in the trial had significantly higher levels of baseline anxiety and depression as compared to subjects who dropped out. Results at week 4 included significant reductions in levels of perceived stress, anxiety, and insomnia; improvements were maintained at week 16. Correlations between number of yoga sessions and post-intervention PSS scores were negative (r = −0.49), and significant (p&amp;lt; 0.05). Both tele-yoga programs proved safe, useful tools to counteract perceived stress, anxiety and insomnia. Future trials should explore the utility of tele-yoga as a tool to enhance well-being and manage stress.