6-month Phase Research Articles

Peer-led recovery groups for people with psychosis in South Africa (PRIZE): Results of a randomized controlled feasibility trial.

The aims of this feasibility trial were to assess the acceptability and feasibility of peer-led recovery groups for people with psychosis in a low-resource South African setting, to assess the feasibility of trial methods, and to determine key parameters in preparation for a definitive trial. The design was an individually randomised feasibility trial comparing recovery groups in addition to treatment as usual (TAU) with TAU alone. Ninety-two isiXhosa-speaking people with psychosis and forty-seven linked caregivers were recruited from primary care clinics and randomly allocated to trial arms in a 1:1 allocation ratio. TAU comprised anti-psychotic medication delivered in primary care. The intervention arm comprised six recovery groups including service users and caregivers. Two-hour recovery group sessions were delivered weekly in a 2-month auxiliary social worker (ASW)-led phase, then a 3-month peer-led phase. To explore acceptability and feasibility, a mixed methods process evaluation included 25 in-depth interviews and 2 focus group discussions at 5months with service users, caregivers and implementers, and quantitative data collection including attendance and facilitator competence. To explore potential effectiveness, quantitative outcome data (functioning, relapse, unmet needs, personal recovery, stigma, health service use, medication adherence and caregiver burden) were collected at baseline, 2months and 5months post randomisation. Trial registration: PACTR202202482587686. Qualitative interviews revealed that recovery groups were broadly acceptable with most participants finding groups to be an enjoyable opportunity for social interaction, and joint problem-solving. Peer facilitation was a positive experience; however a minority of participants did not value expertise by lived experience to the same degree as expertise of professional facilitators. Attendance was moderate in the ASW-led phase (participants attended 59% sessions on average) and decreased in the peer-led phase (41% on average). Participants desired a greater focus on productive activities and financial security. Recovery groups appeared to positively impact on relapse. Relapse occurred in 1 (2.2%) of 46 participants in the recovery group arm compared to 8 (17.4%) of 46 participants in the control arm (risk difference -0.15 [95% CI: -0.26; -0.05]). Recovery groups also impacted on the number of days in the last month totally unable to work (mean 1.4days recovery groups vs 7.7days control; adjusted mean difference -6.3 [95%CI: -12.2; -0.3]). There were no effects on other outcomes. Peer-led recovery groups for people with psychosis in South Africa are potentially acceptable, feasible and effective. A larger trial, incorporating amendments such as increased support for peer facilitators, is needed to demonstrate intervention effectiveness definitively.

Improving the provision of emotional support for patients following major lower limb amputation

Major lower limb amputation (MLLA) is a lifesaving but life-altering surgical procedure. Psychological distress is common and typically heightened in the acute postoperative period. Despite the negative impact that poor...

Telemedicine and Remote Management of Patients with Heart Failure: From Theory to Daily Practice.

Background: Heart failure (HF) is responsible for a high number of hospitalizations, caused by a progressive worsening quality of life. Telemedicine allows for better management of patients' complex conditions, improving the care released. However, the risk of remaining at a testing stage often limits the integration of remote care in daily pathways for HF patients. The aim of this study is to outline the steps needed to integrate telemedicine activities into ordinary HF clinic practices. This methodology is applied to observe activities and trend improvements over a 12-month routine phase. Method: Three steps have been defined for an efficient introduction of remote care services in ordinary activities, integrating them with traditional in-person care: (i) introduction of temporary telemedicine projects, (ii) systematization of telemedicine pathways, and (iii) evaluation of monitoring phase. Observational data have been collected from structured interviews to show the rate of telemedicine activities achieved in clinical practice over the last year. Results: The methodology has been proposed in the HF clinic of the Italian hospital ASST Bergamo Est. After an initial testing phase, in which usability and user experience have been tested, four different remote activities were added: (i) telemonitoring for patients with an implantable device, (ii) follow-up televisits, (iii) nursing telephone support, and (iv) high-intensity telesurveillance pathways for patients after an HF acute event. During the last year, 218 telemonitoring pathways, 75 televisits, 500 telephone calls, and nine telesurveillance pathways have been performed. Success rates were high, and patients gave positive feedback. Conclusion: By integrating multiple telemedicine activities, it has been possible to better manage complex patients, keep track of disease progression, and improve their participation in care.

Training for Elite Team-Pursuit Track Cyclists-Part II: A Comparison of Preparation Phases in Consecutive World-Record-Breaking Seasons.

To compare the training characteristics of an elite team pursuit cycling squad in the 3-month preparation phases prior to 2 successive world-record (WR) performances. Training data of 5 male track endurance cyclists (mean [SD]; age 23.4 [3.46]y; body mass 80.2 [2.74]kg; 4.5 [0.17]W·kg-1 at LT2; maximal aerobic power6.2 [0.27]W·kg-1; maximal oxygen uptake 65.9 [2.89]mL·kg-1·min-1) were analyzed with weekly total training volume by training type and heart rate, power output, and torque intensity distributions calculated with reference to the respective WRs' performance requirements. Athletes completed 805 (82.81) and 725 (68.40)min·wk-1 of training, respectively, in each season. In the second season, there was a 32% increase in total track volume, although track sessions were shorter (ie,greater frequency) in the second season. A pyramidal intensity distribution was consistent across both seasons, with 81% of training, on average, performed below LT1 power output each week, whereas 6% of training was performed above LT2. Athletes accumulated greater volume above WR team pursuit lead power (2.4% vs 0.9%) and torque (6.2% vs 3.2%) in 2019. In one athlete, mean single-leg-press peak rate of force development was 71% and 46% higher at mid- and late-phases, respectively, during the preparation period. These findings provide novel insights into the common and contrasting methods contributing to successive WR team pursuit performances. Greater accumulation of volume above race-specific power and torque (eg,team pursuit lead), as well as improved neuromuscular force-generating capacities, may be worthy of investigation for implementation in training programs.

Telemedical Direction to Optimize Resource Utilization in a Rural Emergency Medical Services System.

Telemedicine remains an underused tool in rural emergency medical servces (EMS) systems. Rural emergency medical technicians (EMT) and paramedics cite concerns that telemedicine could increase Advanced Life Support (ALS) transports, extend on-scene times, and face challenges related to connectivity as barriers to implementation. Our aim in this project was to implement a telemedicine system in a rural EMS setting and assess the impact of telemedicine on EMS management of patients with chest pain while evaluating some of the perceived barriers. This study was a mixed-methods, retrospective review of quality assurance data collected prior to and after implementation of a telemedicine program targeting patients with chest pain. We compared quantitative data from the 12-month pre-implementation phase to data from 15 months post-implementation. Patients were included if they had a chief complaint of chest pain or a 12-lead electrocardiogram had been obtained. The primary outcome was the rate of ALS transport before and after program implementation. Secondary outcomes included EMS call response times and EMS agency performance on quality improvement benchmarks. Qualitative data were also collected after each telemedicine encounter to evaluate paramedic/EMT and EMS physician perception of call quality. The telemedicine pilot project was implemented in September 2020. Overall, there were 58 successful encounters. For this analysis, we included 38 patients in both the pre-implementation period (September 9, 2019-September 10, 2020) and the post-implementation period (September 11, 2020-December 5, 2021). Among this population, the ALS transport rate was 42% before and 45% after implementation (odds ratio 1.11; 95% confidence interval 0.45-2.76). The EMS median out-of-service times were 47 minutes before, and 33 minutes after (P = 0.07). Overall, 64% of paramedics/EMTs and 89% of EMS physicians rated the telemedicine call quality as "good." In this rural EMS system, a telehealth platform was successfully used to connect paramedics/EMTs to board-certified EMS physicians over a 15-month period. Telemedicine use did not alter rates of ALS transports and did not increase on-scene time. The majority of paramedics/EMTs and EMS physicians rated the quality of the telemedicine connection as "good."

The impact of a digital guideline version on schizophrenia guideline knowledge: results from a multicenter cluster-randomized controlled trial

BackgroundClinical practice guidelines are crucial for enhancing healthcare quality and patient outcomes. Yet, their implementation remains inconsistent across various professions and disciplines. Previous findings on the implementation of the German guideline for schizophrenia (2019) revealed low adherence rates among healthcare professionals. Barriers to guideline adherence are multifaceted, influenced by individual, contextual, and guideline-related factors. This study aims to investigate the effectiveness of a digital guideline version compared to print/PDF formats in enhancing guideline adherence.MethodsA multicenter, cluster-randomized controlled trial was conducted in South Bavaria, Germany, involving psychologists and physicians. Participants were divided into two groups: implementation of the guideline using a digital online version via the MAGICapp platform and the other using the traditional print/PDF version. The study included a baseline assessment and a post-intervention assessment following a 6-month intervention phase. The primary outcome was guideline knowledge, which was assessed using a guideline knowledge questionnaire.ResultsThe study included 217 participants at baseline and 120 at post-intervention. Both groups showed significant improvements in guideline knowledge; however, no notable difference was found between both study groups regarding guideline knowledge at either time points. At baseline, 43.6% in the control group (CG) and 52.5% of the interventional group (IG) met the criterion. There was no significant difference in the primary outcome between the two groups at either time point (T0: Chi2(1) = 1.65, p = 0.199, T1: Chi2(1) = 0.34, p = 0.561). At post-intervention, both groups improved, with 58.2% in the CG and 63.5% in the IG meeting this criterion.ConclusionsWhile the study did not include a control group without any implementation strategy, the overall improvement in guideline knowledge following an implementation strategy, independent of the format, was confirmed. The digital guideline version, while not superior in enhancing knowledge, showed potential benefits in shared decision-making skills. However, familiarity with traditional formats and various barriers to digital application may have influenced these results. The study highlights the importance of tailored implementation strategies, especially for younger healthcare providers.Trial registrationhttps://drks.de/search/de/trial/DRKS00028895

Safety and Efficacy of Multiple Escalating Doses of RC28-E for Neovascular Age-Related Macular Degeneration: A Phase 1b Trial.

To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0mg. Patients were evaluated monthly for 48weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48weeks. RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

Study protocol for the Treating Opioid Patients' Pain and Sadness (TOPPS) study — A randomized control trial to lower depression and chronic pain interference, and increase care retention among persons receiving buprenorphine

BackgroundPersons receiving prescription buprenorphine for opioid use disorder experience high rates of comorbid conditions such as chronic pain and depression, which present barriers to buprenorphine care retention. This paper describes the protocol of the TOPPS (Treating Opioid Patients' Pain and Sadness) study, which compares a values-based, behavioral activation intervention with a health education contact-control condition, with the aim of decreasing chronic pain and depression, and increasing buprenorphine care retention for persons with opioid use disorder. MethodsThis randomized controlled trial (RCT) enrolls and randomizes up to 250 participants currently being treated with buprenorphine to receive three months of either TOPPS, a six-session phone-based behavioral intervention, or a health education (HE) control condition. We compare the TOPPS intervention to HE on the following outcomes: 1) pain interference and pain severity over the 3-month treatment phrase; 2) depressive symptoms over the 3-month treatment phase; and 3) sustained improvements in pain interference, depressive symptoms, and buprenorphine treatment retention over the 12-month study period. We also examine mechanisms by which the intervention may reduce pain interference. DiscussionThis RCT explores a novel intervention to address chronic pain and depression for individuals receiving buprenorphine in office-based settings. TOPPS may lead to improved pain, depression, and substance use outcomes, and can utilize providers available within buprenorphine programs, broadening the disseminability of this intervention and heightening its public health impact. Clinical Trial#NCT03698669

A single-arm, open-label phase II clinical trial of SHR-1210 (camrelizumab) in combination with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma.

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.

The allied health rural generalist pathway: a cost consequence analysis.

Rural and remote health workforces face longstanding challenges in Australia. Little is known about the economic effectiveness of workforce initiatives to increase recruitment and retention. A two-level allied health rural generalist pathway was introduced as a workforce strategy in regional local health networks (LHNs) in South Australia in 2019. This research measured the resources and outcomes of the pathway following its introduction. A multi-phase, mixed-methods study was conducted with a 3-year follow-up period (2019-2022). A cost-consequence analysis was conducted as part of this study. Resources measured included tuition, time for quarantined study, supervision and support, and program manager salary. Outcomes measured included length of tenure, turnover data, career progression, service development time, confidence and competence. Fifteen allied health professional trainees participated in the pathway between 2019 and 2022 and seven completed during this time. Trainees participated for between 3 and 42 months. The average total cost of supporting a level 1 trainee was $34,875 and level 2 was $70,469. The total return on investment within the evaluation period was $317,610 for the level 1 program and $58,680 for the level 2 program. All seven completing trainees continued to work in regional LHNs at the 6-month follow-up phase and confidence and competence to work as a rural generalist increased. This research found that the allied health rural generalist pathway has the potential to generate multiple positive outcomes for a relatively small investment and is therefore likely to be a cost-effective workforce initiative.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial

BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.MethodsMIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.ResultsDuring September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.ConclusionsThe multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.Trial registrationClinicalTrials.gov NCT03249688.

Beneficial Effects of Multi-Micronutrient Supplementation with Collagen Peptides on Global Wrinkles, Skin Elasticity and Appearance in Healthy Female Subjects.

With ageing, collagen production slows down, leading to wrinkle appearance and loss of elasticity. Replenishing key structural molecules through oral supplementation is a promising strategy that complements the topical delivery of cosmetic products and creates a holistic skincare regimen. The present study assessed the effectiveness of a food supplement with collagen peptides, vitamins and minerals in improving the quality of the skin and general wellbeing of healthy women. This was an open-label study of 135 women aged between 45 and 65years. A 3-month treatment phase followed a 4-week washout phase, with visits scheduled at baseline and after each month of treatment. Subjects received three tablets of Richelet Skin Renewal daily. The primary outcome was change from baseline to month3 in global wrinkles score by expert grader analysis. Secondary outcomes included changes in skin elasticity and other skin attributes, product assessment via self-perception questionnaires and total antioxidant status. A total of 116 subjects completed the study. The mean global wrinkles score indicated a statistically significant decrease from 5.9 at baseline to 5.0 at month3 (p < 0.0001), with 83.6% of subjects showing an improvement; significant changes were reported at all intermediate visits. The increase in skin elasticity was also statistically significant (R2 score 0.74 at month3; p < 0.0001). All subjects (100%) demonstrated significant improvements in skin texture, skin tone evenness, skin radiance and overall skin quality at the month3 visit. The study product achieved statistically significant, noticeable effects on global wrinkles, skin elasticity and a range of skin attributes after 3months of use in healthy women. These results strengthen the evidence for supplementation of collagen peptides and other micronutrients as an effective component of anti-ageing skincare.

Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed

ABSTRACT Objectives Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Methods NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs. Results NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (−44 [95% CI −328; −21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue. Conclusion Daridorexant 50 mg and 25 mg have a favorable benefit–risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

Importance of treating acne sequelae in skin of color: 6-month phase IV study of trifarotene with an appropriate skincare routine including UV protection in acne-induced post-inflammatory hyperpigmentation.

Acne-induced hyperpigmentation (AIH) may accompany acne vulgaris (AV) inflammation in all skin phototypes. Trifarotene has shown depigmenting properties in vivo. This study evaluated trifarotene plus skincare because it is increasingly recognized that holistic AV management should include skincare and treatments. This is a phase IV double-blind, parallel-group study of patients (13-35 years) with moderate AV and AIH treated with trifarotene (N = 60) or vehicle (N = 63) plus skincare regimen (moisturizer, cleanser, and sunscreen) for 24 weeks. Assessments included the AIH overall disease severity (ODS) score, post-AV hyperpigmentation index (PAHPI), exit interviews, photography, and acne assessments. Standard safety assessments were included. Trifarotene 50 μg/g cream improved significantly from baseline in ODS score versus vehicle (-1.6 vs. -1.1, P = 0.03) at Week 12, but scores were comparable between groups at Week 24 (primary endpoint). Trifarotene had a better reduction in PAHPI score at Week 24 (-18.9% vs. -11.3% vehicle, P < 0.01). Lesion count reductions were higher with trifarotene at Week 12 versus vehicle (P < 0.001) and at Week 24 (P < 0.05), as were IGA success rates versus vehicle at Weeks 12 (P < 0.05) and 24 (P < 0.05). Patients agreed that the skincare regimen contributed to less irritation, making treatment adherence easier. Photography showed improvements in pigmentation and erythema across all skin types. AEs were more common in the vehicle group versus trifarotene (30.2 vs. 16.7%, respectively). In all skin phototypes, there was more rapid improvement in the ODS and PAHPI scores with trifarotene by Weeks 12 and 24, respectively. The combination of trifarotene and skincare correlated with high patient satisfaction and adherence to the treatment protocol.

Performance map of the hydraulic air compressor (HAC) installed at Dynamic Earth, Sudbury

After a 6-month construction phase, the approximately 30m high hydraulic air compressor (HAC) demonstrator facility installed at the Dynamic Earth science centre in Sudbury was officially opened on June 21, 2017. For the first time in the open literature, this paper presents experimental results from a large scale hydraulic air compressor, which proves their performance as an energy efficiency technology for industrial air compression. The temperature rise of air compressed in the HAC downcomer has been repeatedly measured at around 0.010K, experimentally confirming the process to be nearly isothermal. The ratio of mass flow air at intake to mass flow of air at output peaked at 94% for the conditions tested. The theoretical peak efficiency of compression for HAC Demonstrator geometry (predicted to be nearly 73%) was only attained when an in-line air–water mixing system replaced a century-old air–water mixing head design.

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial

The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

Safety and Effectiveness of the High-Sensitivity Cardiac Troponin HEART Pathway in Patients With Possible Acute Coronary Syndrome.

The HEART Pathway (History, Electrocardiogram, Age, Risk factors, Troponin) can be used with high-sensitivity cardiac troponin to risk stratify emergency department patients with possible acute coronary syndrome. However, data on whether a high-sensitivity HEART Pathway (hs-HP) are safe and effective is lacking. An interrupted time series study was conducted at 5 North Carolina sites in 26 126 adult emergency department patients being investigated for possible acute coronary syndrome and without ST-segment-elevation myocardial infarction. Patients were accrued into 16-month preimplementation and postimplementation cohorts with a 6-month wash-in phase. Preimplementation (January 2019 to April 2020), the traditional HEART Pathway was used with 0- and 3-hour contemporary troponin measures (Siemens). In the postimplementation period (November 2020 to February 2022), a modified hs-HP was used with 0- and 2-hour high-sensitivity cardiac troponin (Beckman Coulter) measures. The primary safety and effectiveness outcomes were 30-day all-cause death or myocardial infarction and 30-day hospitalizations. These outcomes and early discharge rate (emergency department discharge without stress testing or coronary angiography) were determined from health records and death index data. Outcomes were compared preimplementation versus postimplementation using χ2 tests and multivariable logistic regression to adjust for potential confounders. Preimplementation and postimplementation cohorts included 12 317 and 13 809 patients, respectively, of them 52.7% (13 767/26 126) were female with a median age of 54 years (interquartile range, 42-66). Rates of 30-day death or MI were 6.8% (945/13 809) postimplementation and 7.7% (948/12 317) preimplementation (adjusted odds ratio, 1.00 [95% CI, 0.90-1.11]). hs-HP implementation was associated with 19.9% (95% CI, 18.7%-21.1%) higher early discharges (post versus pre: 63.6% versus 43.7%; adjusted odds ratio, 2.22 [95% CI, 2.10-2.35]). The hs-HP was also associated with 16.1% (95% CI, 14.9%-17.3%) lower 30-day hospitalizations (postimplementation versus preimplementation, 31.4% versus 47.5%; adjusted odds ratio, 0.51 [95% CI, 0.48-0.54]). Among early discharge patients, death or myocardial infarction occurred in 0.5% (41/8780) postimplementation versus 0.4% (22/5383) preimplementation (P=0.61). hs-HP implementation is associated with increased early discharges without increasing adverse events. These findings support the use of a modified hs-HP to improve chest pain care.

Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT) efficacy trial: Community health worker support may increase hydroxyurea adherence of youth with sickle cell disease.

Despite disease-modifying effects of hydroxyurea on sickle cell disease (SCD), poor adherence among affected youth commonly impedes treatment impact. Following our prior feasibility trial, the "Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT)" multi-site randomized controlled efficacy trial aimed to increase hydroxyurea adherence for youth with SCD ages 10-18years. Impaired adherence was identified primarily through flagging hydroxyurea-induced fetal hemoglobin (HbF) levels compared to prior highest treatment-related HbF. Eligible youth were enrolled as dyads with their primary caregivers for the 1-year trial. This novel semi-structured supportive, multidimensional dyad intervention led by community health workers (CHW), was augmented by daily tailored text message reminders, compared to standard care during a 6-month intervention phase, followed by a 6-month sustainability phase. Primary outcomes from the intervention phase were improved Month 6 HbF levels compared to enrollment and proportion of days covered (PDC) for hydroxyurea versus pre-trial year. The secondary outcome was sustainability of changes up to Month 12. The 2020-2021 peak coronavirus disease 2019 (COVID-19) pandemic disrupted enrollment and clinic-based procedures; CHW in-person visits shifted to virtual scheduled interactions. We enrolled 50 dyads, missing target enrollment. Compared to enrollment levels, both HbF level and PDC significantly - but not sustainably - improved within the intervention group (p=.03 and .01, respectively)with parallel increased mean corpuscular volume (MCV) (p=.05), but not within controls. No significant between-group differences were found at Months 6 or 12. These findings suggest that our community-based, multimodal support for youth-caregiver dyads had temporarily improved hydroxyurea usage. Durability of impact should be tested in a trial with longer duration of CHW-led and mobile health support.

Efficacy of Bowel Regimen in Decreasing Postoperative Constipation in Bariatric Surgery Patients.

Postoperative constipation after bariatric surgery is a common complaint, decreasing patient quality of life. No literature exists examining the efficacy of a preoperative bowel regimen in reducing postoperative constipation in this cohort. This study aims explore the efficacy of a well-established bowel regimen, polyethylene glycol (PEG), in reducing constipation frequency and severity after bariatric surgery. This was a retrospective study of adult patients undergoing primary and revisional bariatric procedures. The use of PEG bowel prep for bariatric patients was introduced as an institutional quality improvement measure. Patients during the first 3months after PEG implementation were surveyed for postoperative constipation. For the year after implementation, patients were followed for 30-day emergency room visits or hospitalization secondary to constipation. This cohort was compared to historical controls from the previous year. Student t-tests were used for statistical analysis. During the 3-month exploratory phase, 28/49 (57.14%) patients fully completed the bowel regimen. In total, 0/56 (0%) patients reported preoperative constipation, and 5/28 (17.9%) patients reported constipation at the 3-week follow-up. In the 1year post-implementation cohort, 2/234 (0.85%) patients had constipation-related occurrences at 30-day follow-up, compared to 8/219 patients (3.65%) in the historical cohort (p = 0.04). The implementation of a PEG-based bowel regimen did not eliminate self-reported constipation. However, there were significant differences in rates of constipation-related ED visits and hospital readmissions, suggesting that the bowel regimen decreases rates of severe constipation. Finally, patient compliance was limited. Future work should aim towards increasing compliance.

Alternating application of gemcitabine/nab-paclitaxel (Gem/nab-Pac) and Gem monotherapy or continuous application of Gem/nab-Pac after induction treatment for first-line treatment of metastatic pancreatic cancer (mPC): First results from the randomized phase 2 ALPACA study from the German AIO study group (AIO-PAK-0114).

605 Background: The aim of the ALPACA study was to investigate whether improved overall tolerability accompanied by prolonged treatment duration and increased efficacy can be achieved by alternating treatment cycles of Gem/nab-Pac and Gem monotherapy compared to standard continuous Gem/nab-Pac after a 3-month induction phase in patients with mPC. Methods: The randomized, multicenter phase 2 ALPACA trial of the German AIO study group enrolled patients with confirmed mPC in the first-line setting. After an induction phase with 3 cycles of standard dose Gem/nab-Pac (Gem 1000 mg/m2 and nab-Pac 125 mg/m2 on d1, 8, 15 of each 28-day cycle), patients were randomized (1:1) either to continue treatment with standard Gem/nab-Pac, or to receive alternating cycles of standard dose Gem/nab-Pac combination therapy and Gem monotherapy (Gem 1000 mg/m2 on d1, 8, 15 of each 28-day cycle). Primary study endpoint was overall survival (OS) after randomization. The trial was registered with ClinicalTrials.gov, NCT02564146. Results: Between May 2016 and May 2021, 325 patients were enrolled from 29 German centers. 6 of the enrolled patients did not start treatment within the study. Following 3 cycles of induction treatment, 174 patients (53.5%) could be randomized. Main reasons for premature dropout were death (24.8%), progression of disease (22.8%), and adverse events (15.9%). Median OS after randomization in the alternating treatment arm was comparable to the standard treatment arm (10.5 vs. 10.4 months; HR 0.903, 80% CI 0.723-1.128, p=0.5551). Likewise, median progression-free survival was comparable in both arms (5.5 vs. 5.3 months; HR 0.767, 95% CI 0.556-1.056, p=0.1017). Tolerability was improved for mPC patients treated with alternating cycles compared to standard therapy, especially regarding peripheral neuropathy (all grades, 44.7% vs. 52.5%), and occurrence of infections (all grades, 29.4% vs. 47.5%). Treatment duration after randomization was similar in both arms (3.25 vs. 3.02 months). Fewer patients receiving alternating treatment cycles dropped out of the study due to adverse events compared to patients treated with continuous Gem/nab-Pac (14.9% vs 27.5%). In return, these patients terminated the study slightly more often due to progression of disease (48.3% vs 42.5%). Conclusions: The ALPACA trial suggests that a dose-reduced regimen with alternating cycles of Gem/nab-Pac and Gem monotherapy after 3 induction cycles of standard Gem/nab-Pac is feasible and associated with an OS comparable to standard treatment while resulting in improved tolerability. Clinical trial information: NCT02564146 .