Post-treatment Time Points Research Articles

Abstract 583: Spatiotemporal analyses of longitudinal specimens reveal mechanisms of response and resistance to immune checkpoint blockade in metastatic melanoma

Abstract Although durable responses to immune checkpoint blockade (ICB) therapies exhibit by a subgroup of patients with metastatic melanoma, most of patients have no response or develop to acquired resistance to ICB therapies within few years. Molecular mechanisms of primary and acquired resistance to ICB therapies are still elusive, which warrants further elucidation. Here, we used a holistic approach to profile 35 longitudinal tumor specimens at pre-, on-, and post-treatment time points which were derived from 7 patients (3 responders and 4 non-responders) with metastatic melanoma who progressed on sequential ICB therapies, including anti-PD-1 and anti-CTLA-4 therapies. We integrated analyses of RNA sequencing, Whole-exome Sequencing (WES), NanoString nCounter vantage 3D, Cyclic Immunofluorescence (Cyc-IF), NanoString Digital Spatial Profiling (DSP) and Multiplex Immunohistochemistry (mIHC) data of these longitudinal tumor specimens to elucidate evolutionary trajectories that occurred in both the tumor and the tumor immune microenvironment (TiME) that may have orchestrated response and resistance to ICB therapies. Simultaneous analyses of genomic, transcriptomic and proteomic data identified the re-activation of MAPK-RAS as well as PI3K pathway upon or after ICB therapies, which may elucidate the mechanism of resistance to ICB therapies. Spatially-resolved, image-based immune monitoring analysis at single cell resolution revealed that the activation status of T cell markers and T-cell checkpoint is conversely associated with potential mechanism of resistance to ICB therapies. In summary, integrated analyses of muti-oics and spatially image-based data from longitudinal tumor specimens allow us not only to reveal the dynamic co-revolution of both tumor and immune cells in TiME following sequential ICB therapies but also to provide a comprehensive perspective to molecular mechanisms of response and resistance to ICB therapies in patients with metastatic melanoma. Citation Format: Gao Zhang, Lisa Coussens, Meenhard Herlyn, Keith T. Flaherty, Genevieve Boland, Gordon Mills. Spatiotemporal analyses of longitudinal specimens reveal mechanisms of response and resistance to immune checkpoint blockade in metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 583.

Abstract 2238: Reducing cardiovascular disease risk in cancer survivors: Impact of a 16-week circuit-based interval exercise intervention

Abstract Introduction: Obesity and physical inactivity pose a significant health concern for cancer survivors in developing comorbid conditions such as type 2 diabetes, hypertension, and metabolic syndrome that lead to a heightened risk of cardiovascular disease (CVD). Therefore, regular physical activity plays a central role in reducing the risk of CVD. The Framingham risk score (FRS) is an established assessment of CVD risk that combines six risk factors including age, gender, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, diabetes, and smoking status. The objective of the study was to investigate the effects of a 16-week circuit, interval-based exercise training intervention on FRS and the 10-year FRS-predicted risk of developing CVD among breast, prostate, and colorectal cancer survivors. Methods: This single center, pilot randomized controlled trial consisted of 90 sedentary, overweight or obese (BMI > 25.0 kg/m2) survivors of breast, prostate or colorectal cancers, randomized to exercise (n=60) or usual care (n=30). The 16-week intervention comprised supervised moderate to vigorous intensity aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) exercise sessions conducted in a circuit-based interval fashion, occurring three times per week. Blood samples were obtained at baseline and post-intervention time points to measure fasting plasma levels of HDL-C and LDL-C, along with resting systolic blood pressure and diagnosis of diabetes. Paired t-test and repeated measure ANOVA were used to determine between-group differences. Results: Participants (age 63.2 ± 10.8 years) were diagnosed with breast (35%), prostate (30%), and colorectal (35%) cancers and consisted of 55% female participants, participants had a mean BMI of 34.7±5.9, and 85% were obese. Chemotherapy and/or radiation therapy was completed by 75% of participants. Retention and adherence rates to exercise were high (100% and 92%, respectively). Compared to usual care, circuit, interval-based exercise significantly reduced total FRS (between group mean difference, -12.0 points p<0.001) and 10-year CVD risk (-10.0%; p<0.001). Conclusions: This study underscores the critical role of circuit-based, interval exercise interventions in mitigating the elevated cardiovascular risk faced by sedentary, overweight, or obese cancer survivors. The significant reduction in FRS components highlights the potential of structured exercise programs to enhance cardiovascular health, thereby reducing the burden of comorbid conditions and CVD risk in cancer survivors. Citation Format: Amber J. Normann, Rebekah L. Wilson, Cami N. Christopher, Mary K. Norris, Simone Cuomo, Christina M. Dieli-Conwright. Reducing cardiovascular disease risk in cancer survivors: Impact of a 16-week circuit-based interval exercise intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2238.

Roflumilast Cream 0.15% in Patients with Atopic Dermatitis: Individual Patient Response from the Pooled INTEGUMENT-1 and INTEGUMENT-2 Phase 3 Trials

Introduction: Roflumilast cream 0.15% is a highly selective phosphodiesterase 4 inhibitor under investigation as a once-daily, nonsteroidal treatment for atopic dermatitis (AD). Pooled safety and efficacy results of two Phase 3 clinical trials (INTEGUMENT-1 and INTEGUMENT-2) in patients with AD have been presented previously. Here we present individual patient responses on the Eczema Area and Severity Index (EASI), which is used to assess disease severity in clinical trials. Methods: INTEGUMENT-1 and INTEGUMENT-2 were identical, randomized, double-blind, vehicle-controlled, 4-week trials of once-daily roflumilast cream 0.15% in patients aged ≥6 with AD (body surface area [BSA] affected: ≥3%). Patients were randomly assigned 2:1 to roflumilast cream 0.15% or vehicle cream. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (score of 0 [Clear] or 1 [Almost Clear] plus ≥2-point improvement from baseline, assessed on a five-point scale ranging from 0 to 4 [Severe]) at Week 4. EASI was assessed as a secondary endpoint. Safety and tolerability were also evaluated. Results: In total, 884 patients received roflumilast 0.15% cream and 453 patients received vehicle cream. Baseline characteristics and demographics were similar between treatment groups. Significantly more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% versus 14.1%; P<0.0001) and vIGA-AD of Clear or Almost Clear (41.1% vs. 21.4%; P<0.0001) at Week 4. Roflumilast treatment significantly improved itch by 24 hours after first application (P<0.0001). At the first post-treatment timepoint evaluated (Week 1), 84.9% of roflumilast-treated patients had a measurable improvement in EASI. By Week 4, 91.5% of patients had a measurable improvement in EASI. Differences favoring roflumilast were also observed at Week 4 for percentages of patients achieving a 50% reduction in EASI (69.2% vs. 44.4%; P<0.0001), 75% reduction (44.5% vs. 21.2%, P<0.0001), 90% reduction (22.4% vs 8.6%; P<0.0001), and 100% reduction (9.8% vs 4.8%; P<0.002). Roflumilast cream had low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. On local tolerability assessments, >95% of investigators reported no evidence of irritation at any time point and >90% of patients reported no or mild sensation after applying roflumilast cream on patient-rated local tolerability assessments. Conclusions: Roflumilast cream 0.15% provided greater improvement in vIGA-AD Success, vIGA-AD of Clear or Almost Clear, itch, and EASI versus vehicle in patients with AD in two Phase 3 trials. Among patients treated with roflumilast cream 0.15%, 91.5% demonstrated an improvement in EASI score by Week 4. Safety and tolerability were favorable, with >90% of roflumilast- and vehicle-treated patients reporting no or mild sensation at the application site at any timepoint. Sponsored by Arcutis Biotherapeutics, Inc. ClinicalTrials.gov Identifiers: INTEGUMENT-1 [NCT04773587]; INTEGUMENT-2 [NCT04773600]

Applying narrative medicine to prepare empathetic healthcare providers in undergraduate pharmacy education in Singapore: a mixed methods study

BackgroundNarrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students.MethodsNarrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students’ empathy using the Jefferson Scale of Empathy– Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students’ emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach.ResultsThere was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 (“Standing in People’s Shoes”) following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students’ motivation and faculty’s perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students’ motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation.ConclusionThis study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients’ perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.

Minimal important change thresholds change over time after knee and hip arthroplasty

ObjectivesThe minimal important change (MIC) reflects what patients, on average, consider the smallest improvement in a score that is important to them. MIC thresholds may vary across patient populations, interventions used, posttreatment time points and derivation methods. We determine and compare MIC thresholds for the Oxford Knee Score and Oxford Hip Score (OKS/OHS) at 3 months postoperatively to 12- and 24-month thresholds in patients undergoing knee or hip arthroplasty. Study Design and SettingThis cohort study used data from patients undergoing total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), or total hip arthroplasty (THA) at a public hospital between February 2016 and February 2023. At 3, 12, and 24 months postoperatively, patients responded to the OKS/OHS and a 7-point anchor question determining experienced changes in knee or hip pain and functional limitations. We used the adjusted predictive modeling method that accounts for the proportion improved and the reliability of the anchor question to determine MIC thresholds and their mean differences between time points. ResultsComplete data were obtained from 695/957 (73%), 1179/1703 (69%), and 1080/1607 (67%) patients undergoing TKA, 474/610 (78%), 438/603 (73%), and 355/507 (70%) patients undergoing UKA, and 965/1315 (73%), 978/1409 (69%), and 1059/1536 (69%) patients undergoing THA at 3, 12, and 24 months, respectively. The median age ranged from 68 to 70 years and 55% to 60% were females. The proportions improved ranged between 83% and 95%. The OKS/OHS MIC thresholds were 0.1, 4.2, and 5.1 for TKA, 1.8, 5.6, and 3.4 for UKA, and 1.3, 6.1, and 6.0 for THA at 3, 12, and 24 months postoperatively, respectively. The reliability ranged between 0.64 and 0.82, and the MIC values increased between three and 12 months but not between 12 and 24 months. ConclusionAny absence of deterioration in pain and function is considered important at 3 months after knee or hip arthroplasty. Increasing thresholds over time suggest patients raise their standards for what constitutes a minimal important improvement over the first postoperative year. Besides improving our understanding of patients’ views on postoperative outcomes, these clinical thresholds may aid in interpreting registry-based treatment outcome evaluations.

Longitudinal analysis of host protein serum signatures of treatment and recovery in pulmonary tuberculosis.

A better understanding of treatment progression and recovery in pulmonary tuberculosis (TB) infectious disease is crucial. This study analyzed longitudinal serum samples from pulmonary TB patients undergoing interventional treatment to identify surrogate markers for TB-related outcomes. Serum that was collected at baseline and 8, 17, 26, and 52 weeks from 30 TB patients experiencing durable cure were evaluated and compared using a sensitive LC-MS/MS proteomic platform for the detection and quantification of differential host protein signatures relative to timepoint. The global proteome signature was analyzed for statistical differences across the time course and between disease severity and treatment groups. A total of 676 proteins showed differential expression in the serum over these timepoints relative to baseline. Comparisons to understand serum protein dynamics at 8 weeks, treatment endpoints at 17 and 26 weeks, and post-treatment at 52 weeks were performed. The largest protein abundance changes were observed at 8 weeks as the initial effects of antibiotic treatment strongly impacted inflammatory and immune modulated responses. However, the largest number of proteome changes was observed at the end of treatment time points 17 and 26 weeks respectively. Post-treatment 52-week results showed an abatement of differential proteome signatures from end of treatment, though interestingly those proteins uniquely significant at post-treatment were almost exclusively downregulated. Patients were additionally stratified based upon disease severity and compared across all timepoints, identifying 461 discriminating proteome signatures. These proteome signatures collapsed into discrete expression profiles with distinct pathways across immune activation and signaling, hemostasis, and metabolism annotations. Insulin-like growth factor (IGF) and Integrin signaling maintained a severity signature through 52 weeks, implying an intrinsic disease severity signature well into the post-treatment timeframe. Previous proteome studies have primarily focused on the 8-week timepoint in relation to culture conversion status. While this study confirms previous observations, it also highlights some differences. The inclusion of additional end of treatment and post-treatment time points offers a more comprehensive assessment of treatment progression within the serum proteome. Examining the expression dynamics at these later time periods will help in the investigation of relapse patients and has provided indicative markers of response and recovery.

An open trial of biofeedback for long COVID

ObjectiveBiofeedback is a therapeutic treatment model that teaches self-regulation of autonomic functions to alleviate stress-related symptoms. “Long COVID” refers to chronic physical and cognitive sequelae post-SARS-CoV-2 infection. This study examined the efficacy of a six-week intervention, consisting of weekly one-hour sessions combining heart rate variability and temperature biofeedback, for alleviating mood symptoms, somatic symptoms and sleep disturbance of patients diagnosed with long COVID. MethodsData were collected from 20 adult participants aged 22–63 (Mage = 44.1, SDage = 12.2) with varying long COVID symptoms. Within this single arm design, 16 of the 20 participants completed all six sessions of biofeedback; 14 completed an assessment at the three-month post-treatment time point. ResultsParticipants self-reported significant improvements in somatic, anxiety, and depressive symptoms, sleep quality, quality of life, and number of “bad days” immediately after the intervention and three months later (Cohen's d effect size (ES) = 1.09–0.46). Reduced number of medical doctor visits (ES = 0.85) and prescription drug use over the last month (odds ratio = 0.33), as well as improved emotional wellbeing (ES = 0.97) were observed at the three-month time point only. ConclusionResults suggest that this short, readily scalable intervention can be potentially efficacious in alleviating symptoms of long COVID. Despite notable improvements, the major limitation of this study is its lack of control group. While a randomized trial merits study, biofeedback appears to be a brief, effective, non-invasive, and low-cost treatment option for patients with chronic somatic symptoms secondary to SARS-CoV-2 infection.Clinicaltrials.govID: NCT05120648

Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid.

Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.

Examining the acceptability and feasibility of the Compassionate Mindful Resilience (CMR) programme in adults living with chronic kidney disease: the COSMIC study findings

BackgroundIndividuals with chronic kidney disease experience difficult physical and psychological symptoms, that impact quality of life, and are at increased risk of anxiety and depression. Access to specialist psychological support is limited. This study aimed to support a new service development project, in collaboration with Kidney Care UK, to implement the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, which provides accessible mindfulness techniques and practices to enhance compassion and resilience, and explore its feasibility for people living with stage 4 or 5 kidney disease and transplant.MethodsA multi-method feasibility design was utilised. Participants over 18 years, from the UK, with stage 4 or 5 kidney disease or post-transplant, and who were not currently undergoing psychotherapy, were recruited to the four-week CMR programme. Data was collected at baseline, post-intervention and three-months post to measure anxiety, depression, self-compassion, mental wellbeing, resilience, and mindfulness. The acceptability of the intervention for a kidney disease population was explored through qualitative interviews with participants, and the Mindfulness Teacher.ResultsIn total, 75 participants were recruited to the study, with 65 completing the CMR programme. The majority were female (66.2%) and post-transplant (63.1%). Analysis of completed outcome measures at baseline and post-intervention timepoints (n = 61), and three-months post intervention (n = 45) revealed significant improvements in participant’s levels of anxiety (p < .001) and depression (p < .001), self-compassion (p = .005), mental wellbeing (p < .001), resilience (p.001), and mindfulness (p < .001).Thematic analysis of interviews with participants (n = 19) and Mindfulness Teacher (n = 1) generated three themes (and nine-subthemes); experiences of the CMR programme that facilitated subjective benefit, participants lived and shared experiences, and practicalities of programme participation. All participants interviewed reported that they found programme participation to be beneficial.ConclusionThe findings suggest that the CMR programme has the potential to improve psychological outcomes among people with chronic kidney disease. Future randomized controlled trials are required to further test its effectiveness.

Quality of Life in Locally Advanced Carcinoma Rectum Patients During Various Phases of NACRT: An Indian Perspective.

In low- and middle-income countries (LMICs) including India, cancer patients have a poor prognosis because of late diagnosis and cases already grown to advanced stages, low cancer awareness and skewed cancer care facilities. In India, the incidence of colorectal cancer (CRC) is ranked the 4th most common (6.4%) in males and the 5th most common (3.4%) in females. The improvement in the cure rate of rectal cancer has increased life expectancy, and assessment of the quality of life (QoL) in these patients has become a fundamental requirement. Little is known about how the patients perceive these adverse effects during curatively intended radiotherapy. Although studies have investigated the various adverse effects that can occur with radiotherapy and chemotherapy in carcinoma rectum patients, these have not yet been critically appraised and synopsized to form a comprehensive review of their prevalence and effects on QoL. The study was designed to explore the QoL issues in locally advanced carcinoma rectum patients during various phases of neoadjuvant concurrent chemo-radiotherapy (NACCRT). The study was performed over a period of 2years at a single super speciality cancer hospital in North India. Patients were selected as per the inclusion criteria and followed up with a standard questionnaire incorporating various aspects depicting QoL. The interview technique was used for collecting QoL data at four points, at baseline, midway during treatment, at the end of treatment and 4weeks after completion of NACCRT, using EORTC QLQ C30, for QLQ CR29. Special care was taken to avoid observer bias in cases of language issues, and interpreters' services were utilised, and compared with the baseline pre-treatment scores, patients reported a statistically significant and large clinically meaningful change in the global health status, social functioning, fatigue (FACIT-F), appetite loss, anxiety, sore skin and male and female sexual function at the post-treatment time point. Statistically significant changes with moderate clinically meaningful changes were reported for the functional scales-physical, role and emotional functioning of the QLQ C30 questionnaire and body image and weight of the CR29 questionnaire. Similar moderate clinical changes were found in the symptom scales-fatigue, nausea and vomiting, insomnia, constipation and diarrhoea of QLQ C30 and stool frequency, embarrassment with bowel function, impotence and dyspareunia. These parameters returned to almost the pre-treatment values after 4weeks of completion of NACRT. Since QoL is a relatively subjective variable, differences in human race, culture, education and social environment will have impacts on the results. International cooperation is needed to study the QoL in patients with multiple cultural backgrounds. The existing QoL questionnaire tools have been designed with Western countries in mind, and we did face multiple social issues. We suggest that many similar multicentre studies shall be required to essentially tap the accurate QoL-related issues keeping in mind the diverse social, economic, racial and educational backgrounds. As we deal with the ever-increasing cancer menace and better life expectancy, QoL issues shall be a major determinant of treatment success besides primary treatment. These factors should form an integral part of treatment modality, and adequate counselling must be performed prior to initiation of care.

Predicting response to neoadjuvant chemotherapy with liquid biopsies and multiparametric MRI in patients with breast cancer

Accurate prediction of response to neoadjuvant chemotherapy (NAC) can help tailor treatment to individual patients’ needs. Little is known about the combination of liquid biopsies and computer extracted features from multiparametric magnetic resonance imaging (MRI) for the prediction of NAC response in breast cancer. Here, we report on a prospective study with the aim to explore the predictive potential of this combination in adjunct to standard clinical and pathological information before, during and after NAC. The study was performed in four Dutch hospitals. Patients without metastases treated with NAC underwent 3 T multiparametric MRI scans before, during and after NAC. Liquid biopsies were obtained before every chemotherapy cycle and before surgery. Prediction models were developed using penalized linear regression to forecast residual cancer burden after NAC and evaluated for pathologic complete response (pCR) using leave-one-out-cross-validation (LOOCV). Sixty-one patients were included. Twenty-three patients (38%) achieved pCR. Most prediction models yielded the highest estimated LOOCV area under the curve (AUC) at the post-treatment timepoint. A clinical-only model including tumor grade, nodal status and receptor subtype yielded an estimated LOOCV AUC for pCR of 0.76, which increased to 0.82 by incorporating post-treatment radiological MRI assessment (i.e., the “clinical-radiological” model). The estimated LOOCV AUC was 0.84 after incorporation of computer-extracted MRI features, and 0.85 when liquid biopsy information was added instead of the radiological MRI assessment. Adding liquid biopsy information to the clinical-radiological resulted in an estimated LOOCV AUC of 0.86. In conclusion, inclusion of liquid biopsy-derived markers in clinical-radiological prediction models may have potential to improve prediction of pCR after NAC in breast cancer.

Roflumilast Cream 0.3% in Patients with Chronic Plaque Psoriasis: Individual Patient Response from the Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

Roflumilast cream 0.3% in patients with chronic plaque psoriasis: individual patient response from the pooled DERMIS-1 and DERMIS-2 phase 3 trials&#x0D; &#x0D; James Del Rosso1 on behalf of the authors&#x0D; &#x0D; INTRODUCTION: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. The efficacy and safety of the pooled results of two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) in patients aged ≥2 years with plaque psoriasis have been previously presented. We present individual patient responses using the Psoriasis Area and Severity Index (PASI).&#x0D; METHODS: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% of body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8; IGA of Clear or Almost Clear was a secondary endpoint. PASI was used to measure disease severity; individual patient PASI responses were plotted graphically. Safety and tolerability were also evaluated and have been previously reported.&#x0D; RESULTS: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P&lt;0.0001) and IGA of Clear or Almost Clear (48.0% vs. 9.5%; nominal P&lt;0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P&lt;0.0001), 75% reduction (40.3% vs. 6.5%, P&lt;0.0001), 90% reduction (19.7% vs 2.3%; P&lt;0.0001), and 100% reduction (12.3% vs 0.8%; P&lt;0.001). At the first post-treatment timepoint evaluated (Week 2), 85.7% of roflumilast-treated patients had a measurable improvement in PASI, increasing to 95.0% by the last timepoint (Week 8). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. Approximately 96% of patients reported no or mild sensation after the first application of roflumilast cream 0.3%, improving to more than 99% of patients at Week 4 and Week 8, similar to vehicle.&#x0D; CONCLUSIONS: Roflumilast cream 0.3% provided greater improvement in IGA Success, IGA of Clear or Almost Clear, and PASI versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials.&#x0D; Sponsored by Arcutis Biotherapeutics, Inc.&#x0D; ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389

Effects of the combination of pulsed electromagnetic field with progressive resistance exercise on knee osteoarthritis: A randomized controlled trial.

Knee osteoarthritis (OA) is a common and disabling disease among the elderly population. The optimal conservative treatment for knee OA is not well established. This study aimed to assess the effectiveness of pulsed electromagnetic field (PEMF) combined with progressive resistance exercise (PRE) in improving physical function and pain in patients with knee OA. Thirty-four patients with knee OA (17 in each group) participated in a single-blind randomized control study. Patients were randomly assigned to receive 24 sessions of either combined PEMF and PRE (treatment group) or PRE only (control group). Patients were evaluated at pre-treatment, post-treatment (2 months), and at 3-month and 6-month follow-ups using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Numeric Pain Rating Scale (NPRS); walking speed and 5-times chair stand test. Mixed ANOVA was used for statistical analysis with Bonferroni adjustments. There was no significant group-by-time interaction for any outcome (P> 0.05). However, both groups scored significantly higher on the NPRS and KOOS at post-treatment, 3-, and 6-month follow-up compared to their baseline. Further, both groups completed the 5-times chair stand test and walking speed test with significantly less time at all post-treatment time points than the pre-treatment. None of the study outcomes (NPRS, KOOS, walking speed, and 5 times chair stand) were significantly different between groups at any of the time points. Both treatment options, PRE only versus PRE with PEMF, were equally effective in decreasing pain and improving physical function in patients with knee OA. This would suggest that the optimal parameters for PEMF that may show beneficial effects for knee OA when added to PRE training need to be determined.

Adjunctive transcranial direct current stimulation to improve swallowing functions in Parkinson's disease.

Swallowing problems are frequent in Parkinson's disease (PD). The aim of this study was to determine the effectiveness of combined transcranial Direct Current Stimulation (tDCS) and Conventional Dysphagia Therapy (CDT) on dysphagia in PD patients. Twenty PD patients with dysphagia were randomized into two groups: combination therapy (anodal tDCS plus CDT) and sham tDCS combined with CDT. Anodal or sham tDCS, bilaterally over the pharyngeal motor cortex, was applied with one mA during the first 20 min (real) or 30 s (sham) of CDT, which was delivered for 30 min. Both groups received twice-daily treatment sessions within two weeks. Swallowing functions were evaluated before, immediately, and one month after the intervention via the Penetration-Aspiration Scale (PAS), and the Swallowing Disorder Questionnaire (SDQ) as the primary outcome measures, and the Dysphagia Handicap Index (DHI) as the secondary outcome measure. The results showed a significant improvement of PAS scores from baseline to post-intervention and baseline to follow-up in both groups without significant differences between groups (t=0.03, p=0.973, and t=1.27, p=0.22 for post-intervention and follow-up time points, respectively). The results showed a significant reduction of SDQ and DHI scores in both groups after the intervention, but the magnitude of the change was significantly larger in the anodal tDCS group at the post-intervention (ta=2.58, pa=0.019 and tb=2.96, pb=0.008) and follow-up (ta=2.65, pa=0.016 and tb=2.97, pb=0.008) time points. This study provides preliminary evidence that bi-hemispheric anodal tDCS combined with CDT enhances swallowing functions in patients with Parkinson's disease more than CDT alone.

Efficacy evaluation of acupuncture combined with pricking blood therapy in the treatment of chronic spontaneous urticaria: a randomized controlled trial.

To assess the efficacy of combining acupuncture with pricking blood therapy to treat chronic spontaneous urticaria (CSU) and compare its outcomes with those of second-generation H1-antihistamines. Seventy CSU patients were enrolled and randomly assigned to receive treatment with either oral loratadine tablets or a combination of acupuncture and pricking blood therapy (n=35 each). Evaluations were conducted at baseline, at the conclusion of the 4-week treatment period, and at the 4th and 8th weeks post-treatment time points. We used six scales to gauge the severity of the skin lesions, itchiness, quality of life, and emotional and sleep states of the CSU patients. Upon completion of the treatment, both groups demonstrated a significant reduction in the scores of six scales from the baseline (P < 0.05). Notably, the scores of the itch visual analog scale (VAS), Hamilton Anxiety Scale, and Hamilton Depression Scale in the acupuncture and pricking blood therapy group were lower than those in the loratadine group (all P < 0.05). At the 8-week follow-up, the scores for all six scales were reduced from baseline in both groups (all P < 0.05), though the acupuncture and pricking blood therapy group showed significantly lower scores on the 7-day urticaria activity scale, with the Dermatology Life Quality Index, and the itchiness VAS compared with the loratadine group (all P < 0.05). Acupuncture combined with pricking blood therapy significantly ameliorated skin lesions, itchiness, and the associated psychological distress in CSU patients. This integrative approach not only matched the short-term efficacy of oral loratadine but surpassed its long-term benefits.

Acute effects of energy drink on arterial stiffness and endothelial function in young male bodybuilders with habitual caffeine consumption

Elite bodybuilders consume energy drink (ED) immediately before or during strength training. However, the effects of ED on cardiovascular responses have not been fully understood. In this study, the carotid-femoral pulse wave velocity (cfPWV) and flow-mediated dilation (FMD), which are indices of arterial stiffness and endothelial function in response to acute ED consumption, were examined. Forty-five young men (30.0 ± 3.9 years) were investigated: sedentary (CON, n = 15), physically active (PA, n = 15), and bodybuilders (BD, n = 15). After they consumed commercial ED, their vascular function was analyzed at the following time points: pre, post, 30 min and 60 min. At baseline, the age, height and systolic and diastolic blood pressure of the groups did not significantly differ; conversely, their weight, body mass index, lean mass, fat percent and grip strengths significantly differed (p &lt; 0.05). After ED consumption, central and peripheral blood pressure markedly increased in the PA and CON groups (p &lt; 0.05) but not in the BD group. cfPWV, augmentation index and wave reflection were not different among the groups and did not change at any time point (p &gt; 0.05). However, FMD notably differed among the groups after ED consumption. The FMD of the BD group increased sharply and significantly after ED consumption at post-time points (pre, 6.5% ± 1.7%; post, 13.1% ± 2.6%; 30 min, 10.7% ± 2.9%; 60 min, 8.9% ± 2.4%, p = 0.001). The FMD markedly increased after ED consumption in the PA group (p = 0.004), but it did not change in the CON group (p &gt; 0.05). ED consumption acutely triggered the increase in endothelial function in the BD and PA groups. Therefore, these findings helped elucidate the distinct cardiovascular responses to ED intake among different populations with varying physical activity or training levels.

Protocol for a Pilot Study on the Neurocardiac Mechanism of an Interoceptive Compassion-Based Heart-Smile Training for Depression.

Heart-Smile Training (HST) is an interoceptive compassion-based behavioral intervention that in case reports has been beneficial for depression. Interoception refers to the awareness and regulation of physiological signals from inside the body. Depressed patients often have diminished interoceptive awareness and often experience disconnection from bodily needs and sensations. In addition to interoceptive dysfunction, depression often involves negative self-evaluation and self-critical rumination. HST is a compassion-based meditation training program that explicitly cultivates interoceptive awareness of the heart area. This study aims to investigate the possible neurocardiac mechanisms engaged through HST for depression patients. We plan to enroll 50 subjects to be randomized into a 4-week HST intervention group and a waitlist group. A battery of psychological questionnaires will be administered at baseline and post-intervention timepoints, and electroencephalography (EEG) will be collected during compassion meditation guided by pre-recorded audio. The primary clinical outcome measures are on the feasibility of the intervention and research procedures, the primary mechanistic outcome measure is the post-intervention change in Heartbeat Evoked Potential (HEP) amplitude. Secondary outcome measures include changes in depression severity and EEG gamma spectral activity. Exploratory outcome measures include effects of HST on skin conductance response, heart rate variability, EEG spectral properties in other frequency bands, as well as a list of psychological questionnaires that measure depression and anxiety symptoms, emotion regulation, mindfulness, interoceptive awareness, self-compassion, gratitude, sleep quality, quality of life and social connectedness. Results not yet available. This is the first study on the feasibility and interoceptive neurocardiac mechanism of HST. Our findings will provide frontier knowledge on the physiological working mechanism of behavioral interventions with an interoception-based meditative approach. https://clinicaltrials.gov/study/NCT05564533.

Systematic literature review of treatments used for refractory or unexplained chronic cough in adults.

Refractory or unexplained chronic cough (RCC or UCC) is difficult to manage and is usually treated by the off-label use of drugs approved for other indications. The objectives of this systematic literature review (SLR) were to identify and characterize the current published body of evidence for the efficacy and safety of treatments for RCC or UCC. The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The SLRs pre-defined population included patients ≥18 years of age who were diagnosed with chronic cough. The review was not restricted to any intervention type or study comparator, nor by timeframe. A total of 20 eligible publications from 19 unique trials were included. Seventeen of these trials were randomized controlled trials and most (14/17) were placebo-controlled. There was considerable variability between trials in the definition of RCC or UCC, participant exclusion and inclusion criteria, outcome measurement timepoints, and the safety and efficacy outcomes assessed. Several trials identified significant improvements in cough frequency, severity, or health-related quality of life measures while participants were on treatment, although these improvements did not persist in any of the studies that included a post-treatment follow-up timepoint. In the absence of an approved therapy, placebo remains the most common comparator in trials of potential RCC or UCC treatments. The between-study comparability of the published evidence is limited by heterogeneity of study design, study populations, and outcomes measures, as well as by concerns regarding study size and risk of bias.

Bridging didactic and clinical in nursing education: An innovative health assessment activity

BackgroundAssessment skills are foundational for nursing education to support quality patient care and outcomes across the lifespan. The aim of this activity was to increase knowledge and confidence in performing age-related focused assessments across the lifespan, recognizing cues to differentiate between potential conditions, and documenting findings appropriately. The Situated Cognitive Theory guided the development of the activity. InnovationFaculty developed a comprehensive review activity of focused assessments across the lifespan using scenarios with low and high-fidelity manikins in a classroom setting. Students completed a pre- and post-survey on their perceptions of knowledge and confidence and suggestions for improvements. ImplicationsThe number of positive responses increased for all questions and demonstrated a statistically significant change in perceived knowledge and confidence from pre- to post-time points. Students reported enjoyment of the hands-on approach and application of course content in a realistic setting. ConclusionOverall, students’ perceived knowledge of lifespan assessments increased and voiced an enhanced connection between readings and patient care. The usage of technology-enhanced scenarios shows the potential to augment student learning in prelicensure nursing curricula.

Robotic stereotactic radiosurgery with CyberKnife - brain metastases and fibrinolysis.

Deviations in haemostasis are found in about 50% of patients with cancer and up to 90% of those with metastatic disease. Many studies investigate the dynamics of the processes of coagulation and fibrinolysis and their role as apredictor of therapeutic response, early relapse, or metastasis risk. To investigate the serum levels of urokinase plasminogen activator (uPA) in patients with brain metastases treated with robotic stereotactic radiosurgery (SRS) with CyberKnife. Serum levels of urokinase plasminogen activator (uPA) were measured in 66patients with solid tumours, divided into two groups, with oligometastatic disease and brain metastases. In this prospective longitudinal study, the serum levels of uPA were measured before starting the therapy and at the first, third, and sixth months after patients were irradiated with the CyberKnife system. Analysis of serum uPA levels in the post-treatment period showed astatistically significant decrease between the baseline and the 6 months post-treatment time point in both patient groups. The baseline value of serum uPA in the group with lung cancer decreased by 62.7%, and in the group with other types of cancer - by 60%. Despite the significant reduction of serum uPA levels 6 months after the treatment, the levels remained significantly higher in both groups than in healthy controls. Ongoing research on uPA and cancer will enrich our knowledge and expand the possibilities for clinical utilization of the marker in the oncology setting (Tab. 2, Ref. 18).