Intervention Arm Research Articles

More Efficient Smaller Multi-Cancer Screening Trials.

The NHS-Galleri trial has demonstrated feasibility for multi-cancer screening trial design where all participants provide a 'sample' for screening, but only samples from the intervention arm are tested and acted upon during the trial. We assess efficiency of analysis methods when the control arm may be retrospectively tested at time of analysis. Analyses considered are: (1, traditional) by randomised allocation with all events included; (2, 'intended-effect') nested in those who tested positive in both arms and all events therein; and (3, targeted) by randomised allocation but with endpoint 'test-positive event'. They are compared using approximate statistical methods and scenario analysis. Provided the number who die from cancer after a test-positive sample is a small fraction of the total number who die from cancer, intended-effect and targeted analyses require a much smaller sample size to evaluate cancer-specific mortality than the traditional approach. Intended-effect analysis has a smaller sample size requirement than targeted analysis. This gain is only substantial when the risk of cancer death in test positives is high. Intended-effect or targeted analysis will substantially reduce the sample size needed to evaluate cancer-specific mortality in blood-based screening trials. Targeted analysis requires many fewer retrospective tests and avoids potential effects of needing to inform those whose stored samples test positive. Trialists should consider the trade-off of costs between sample size and retrospective testing requirements when choosing the analysis.

Reducing readmissions with pharmacist-integrated care in Medicare value-based programs.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Pharmacy transitions of care (ToC) programs have been shown to decrease 30-day hospital readmissions and improve patient outcomes, but there is limited published data on the impact of pharmacist-integrated ToC services beyond 30 days. The objective of this study was to evaluate the impact of pharmacist-integrated ToC and population health services on 30-, 60-, and 90-day all-cause readmissions in a Medicare value-based program (MV-BP) population and to compare mean times to first readmission with and without pharmacist care. A retrospective observational chart review was conducted to identify eligible hospital discharge encounters (DEs). Patients 18 years of age or older enrolled in an MV-BP were assigned to 4 study groups (a control group or one of 3 intervention arms) based on the pharmacy ToC services they received from either an inpatient ToC pharmacist or a dedicated population health pharmacist (PHP). Among 1,065 eligible DEs, 90-day follow-up was completed in 1,039 cases. The control group (n = 213) had a 90-day readmission rate of 34.74%. Intervention arm 1 (n = 201) had no significant reduction in 90-day readmissions, with a rate of 29.85% (odds ratio [OR], 0.94; 95% CI, 0.61-1.47; P = 0.80), while intervention arms 2 (n = 209), and 3 (n = 416) had significantly lower rates of readmission: 9.57% (OR, 0.26; 95% CI, 0.15-0.46; P < 0.01), and 17.07% (OR, 0.41; 95% CI, 0.27-0.61; P < 0.01), respectively. A combination of ToC and PHP services reduced 30-, 60-, and 90-day readmission rates in an MV-BP population. These results support the expansion of pharmacy-based ToC to minimize readmissions within 90 days for this Medicare population.

Effectiveness of Play Therapy Programme in Promoting Early Child Development of under-5 Children visiting Tertiary Care Hospital in Rural Settings: Study Protocol of a Randomized Controlled Trial.

Background Good care and conscious, mindful parenting are the essential requirements of the early childhood period. Good care in early childhood consists of mindful handling of children’s needs like hunger, care in sickness, socio-emotional needs, safety, love and affection. Good care promotes children’s development and provides a favourable environment for learning. It’s a well-known fact that hospitalization is a stressful situation for child of any age. Play is an integral part of early childhood period which is virtually restricted in hospital settings. This study will try to explore the effectiveness of play therapy delivered in hospital settings, on early child development. Methods This will be a randomized control trial conducted in the Paediatrics department of a tertiary care hospital in Wardha, India. The sample size will be 360 children, 180 each in intervention and control arm. The hospitalized children from intervention arm will receive customized Play Therapy sessions from trained research assistants and will be followed up at scheduled home visits for one year from the date of enrolment. All children will be assessed for changes in cognitive, motor and socio-emotional development scores. The differences in development scores between intervention and control groups will be compared and effect sizes of changes will be calculated. Discussion Implementation of play stimulation activities have been reported as useful strategies for promoting child development and good recovery during hospitalization. This trial will attempt to explore the effectiveness of play therapy on changes in child development scores of children from intervention group compared to the control group. The customized play therapy program will be adapted to paediatric inpatient settings, and attempts will be made to improve the Play Therapy kit for hospitalized children. Registration Clinical Trial Registry of India Registration No.: C.T.R.I./2022/03/041355, dated 24/03/2022. Protocol Version: v6 Dated 04/10/2024.

Online Mental Health Assessment in a psychiatry emergency department in adults using touchscreen mobile devices: A randomised controlled trial.

To determine whether completion of an online mental health self-assessment by patients who are waiting in the emergency department can save clinician time taken to complete clinical assessment and documentation. Patients presenting to a psychiatric emergency department for a period of 6 months were allocated by week of presentation to either the intervention arm (online mental health self-assessment, followed by a clinical interview) or the control arm (usual assessment) arm on a random basis. Time at the beginning and end of the interview was recorded and used to derive interview time. Similarly, time at the beginning and end of the clinical documentation was recorded and used to derive the time to complete clinical documentation. Of 168 patients who presented during the study period, 69 (38.55%) agreed to participate, 33 completed the usual assessment and 30 completed the online mental health self-assessment followed by a clinical interview. Patients receiving usual care had a statistically significant, t(61) = 2.15, p = 0.035, longer interview duration (M = 48.7 minutes, SD = 19.8) compared with those in the online mental health self-assessment arm (M = 38.9 minutes, SD = 15.9). There was no statistically significant difference between groups for documentation time, t(61) = -0.64, p = 0.52. Online mental health self-assessment was associated with a statistically significant reduction in interview time by approximately 10 minutes without increasing documentation time. While online mental health self-assessment is not appropriate for all patients in the emergency department setting, it is likely to yield greater benefits in less acute settings.

Effectiveness of a multidimensional collaborative approach versus usual care in the treatment of adult depression in primary care in Chile: study protocol for a single blinded cluster randomized controlled trial.

Major depression (MD) is a prevalent and disabling condition in Chile, with most cases being treated at the primary care level. In Chilean primary care, the authors have identified key factors associated with more complex presentations of MD and a poorer prognosis, such as a history of childhood trauma, suicidality, and comorbidities. These findings underscore the need for a multidimensional, trauma-informed, and interprofessional approach to the treatment of depression. This protocol is a two-arm, single-blinded, cluster RCT to compare the effectiveness of a collaborative multidimensional approach for depression (CMAD) versus usual care to treat MD in primary care clinics in Chile. In total, 394 depressed adults from 18 to 65 years of age in twelve clinics located in Chile's Maule Region will be consented to participate in the study. Patients and care teams from each clinic will be randomized to the intervention or to the control arm.Interprofessional teams in the intervention arm will attend 27 hours of didactic and active learning sessions focused on clinical competences to effectively engage, treat and follow up patients with the factors associated to the complex presentation of MD. Team in the control arm will receive 27 didactic sessions on current clinical guidelines for MD.Patients of both arms will be blindly assessed at baseline, three months, and six months. The primary outcome will be the reduction in depressive symptoms, with secondary outcomes including improvements in anxiety symptoms, interpersonal and social functioning, and treatment adherence. This protocol proposes the evaluation of an intervention designed to improve depression symptoms by enhancing the clinical competencies of primary care teams. These competencies are structured around collaborative care and trauma-informed practices. NCT05016388, registered on 16 August 2021 at ClinicalTrials.gov.

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.

Transient Ischaemic attack Emergency Referral (TIER): randomised feasibility trial results

BackgroundEarly assessment of patients with suspected transient ischaemic attack (TIA) is crucial to provision of effective care, including initiation of preventive therapies and identification of stroke mimics. Many patients with...

Effect of the Communities That HEAL Intervention on Overdose Education and Naloxone Distribution: A Cluster-Randomized, Wait-List Controlled Trial.

Objectives. To determine whether the Communities That HEAL (CTH) intervention is effective in increasing naloxone distribution compared with usual care. Methods. The HEALing (Helping to End Addiction Long-Term) Communities Study (HCS) is a cluster-randomized, parallel-arm, wait-list controlled implementation science trial testing the impact of the CTH intervention on increasing the use of evidence-based practices to lower opioid-related overdose deaths. Communities (n = 67) highly impacted by opioid overdose in Kentucky, Massachusetts, New York, and Ohio were allocated to CTH intervention (n = 34) or wait-list comparison (usual care; n = 33) arms. The primary outcome for this study was the number of naloxone units distributed in HCS communities during the comparison period (July 1, 2021‒June 30, 2022), examined using an intent-to-treat negative binomial regression model. Results. Naloxone distribution was 79% higher in the CTH intervention versus usual care arm (adjusted relative rate = 1.79; 95% confidence interval = 1.28, 2.51; P = .001; adjusted rates of naloxone distribution 3378 vs 1884 naloxone units per 100 000 residents), when controlling for urban‒rural status, state, baseline opioid-related overdose death rate, and baseline naloxone distribution rate. Conclusions. The CTH intervention increased naloxone distribution compared with usual care in communities highly impacted by the opioid crisis. Trial Registration. ClinicalTrials.gov identifier: NCT04111939. (Am J Public Health. Published online ahead of print October 10, 2024:e1-e12. https://doi.org/10.2105/AJPH.2024.307845).

Mlambe economic and relationship-strengthening intervention for alcohol use decreases violence and improves relationship quality in couples living with HIV in Malawi

IntroductionA syndemic of unhealthy alcohol use, intimate partner violence (IPV), and economic insecurity threatens to derail progress towards UNAIDS 95-95-95 targets in sub-Saharan Africa. We developed a combined economic and relationship-strengthening intervention called Mlambe to reduce unhealthy alcohol use and increase adherence to antiretroviral therapy for couples in Malawi. This study evaluates the additional impact of Mlambe on IPV and relationship dynamics. MethodsIn a pilot randomized controlled trial, 78 married couples (156 individuals) living with HIV and reporting unhealthy alcohol use based on the AUDIT-C (at least one partner) were recruited from HIV care clinics in Zomba, Malawi. The intervention arm (39 couples) received a 10-month program consisting of incentivized savings accounts with financial literacy education, relationship education, and couples counseling sessions to build relationship skills. The control arm (39 couples) received enhanced usual care (EUC) with brief alcohol counseling. We used linear mixed-effects models to assess the effects of Mlambe on relationship quality (e.g., constructive communication, unity, sexual satisfaction) and IPV (physical, sexual, and emotional) by including fixed effects for treatment arm and a random effect for dyad, and tested whether effects on IPV and relationship quality differed by gender. ResultsAt 10- and 15-month follow-up visits, couples in the Mlambe arm showed greater increases in couple communication, unity, sexual satisfaction, intimacy, and trust (Cohen's d ranged from 0.36 to 0.56; p < 0.05) as compared to EUC. Couples in the Mlambe arm also showed significant decreases in physical and emotional IPV (Cohen's d ranged from 0.33 to 0.49; p < 0.05) as compared to EUC. Subsequent moderation analyses indicated that women reported significantly greater improvements in relationship quality than men, except for sexual satisfaction (p < 0.05), and greater declines in physical IPV than men (p < 0.05). ConclusionsMlambe resulted in significant improvements in relationship quality and decreased IPV in couples, particularly for women who as a group reported lower relationship quality at baseline. Economic and relationship-strengthening interventions have potential to disrupt harmful syndemics of violence, substance use, and poverty among couples living with HIV. Clinical trial numberNCT#04906616.

A Complex Meta-Regression Model to Identify Effective Features of Interventions From Multi-Arm, Multi-Follow-Up Trials.

Network meta-analysis (NMA) combines evidence from multiple trials to compare the effectiveness of a set of interventions. In many areas of research, interventions are often complex, made up of multiple components or features. This makes it difficult to define a common set of interventions on which to perform the analysis. One approach to this problem is component network meta-analysis (CNMA) which uses a meta-regression framework to define each intervention as a subset of components whose individual effects combine additively. In this article, we are motivated by a systematic review of complex interventions to prevent obesity in children. Due to considerable heterogeneity across the trials, these interventions cannot be expressed as a subset of components but instead are coded against a framework of characteristic features. To analyse these data, we develop a bespoke CNMA-inspired model that allows us to identify the most important features of interventions. We define a meta-regression model with covariates on three levels: intervention, study, and follow-up time, as well as flexible interaction terms. By specifying different regression structures for trials with and without a control arm, we relax the assumption from previous CNMA models that a control arm is the absence of intervention components. Furthermore, we derive a correlation structure that accounts for trials with multiple intervention arms and multiple follow-up times. Although, our model was developed for the specifics of the obesity data set, it has wider applicability to any set of complex interventions that can be coded according to a set of shared features.

Effect of antenatal Chlamydia trachomatis and Neisseria gonorrhoeae screening on postdelivery prevalence and vertical transmission in Gaborone, Botswana: findings from an exploratory study

ObjectivesChlamydia trachomatis and Neisseria gonorrhoeae are common sexually transmitted infections (STIs). Untreated infection in pregnancy can result in adverse neonatal outcomes, including vertical transmission. Screening for these infections is not...

Enriching Clinical Trials Enrolling Children With Cerebral Malaria Using Admission Demographics, Physical Examination and Point-of-care Testing Results.

Multiple clinical trials evaluating therapies for cerebral malaria (CM) have failed to demonstrate improved outcomes. This may derive from inclusion of children at all risk levels, including those at low risk of mortality or neurologic morbidity, limiting power to detect significant differences between intervention arms. One solution is enrichment, enrolling clinical trial participants at higher risk of adverse outcomes. We assessed if demographic, physical examination and point-of-care laboratory testing results in combination could identify children with CM at higher risk of death or neurologic disability. Retrospective case-control study of 1674 children hospitalized with CM in Blantyre, Malawi. We used univariate and multivariate analyses of admission factors to find the most parsimonious model associated with death or neurologic disability. To assess the clinical utility of the models, we evaluated derived probability density curve separation. Blantyre Coma Score (BCS), deep breathing and high blood lactate were independently associated with mortality. The derived receiver operating curve yielded an area under the curve of 0.7118. There was poor separation of derived probability density curves predicting death or survival, indicating limited clinical utility of this model. On multivariate modeling of neurologic sequelae in CM survivors, only BCS was associated with adverse outcomes (area-under-the-curve = 0.6151). Probability density curves again largely overlapped, demonstrating limited utility of BCS alone in outcome prediction. Combinations of admission demographic, clinical and point-of-care laboratory factors are inadequate to predict prognosis in children with CM. Higher technology assessment methods are necessary for clinical trial enrichment.

Impact of early continuous positive airway pressure in the delivery room (DR-CPAP) on neonates < 1500 g in a low-resource setting: a protocol for a pilot feasibility and acceptability randomized controlled trial

BackgroundPreterm birth is the leading cause of childhood mortality, and respiratory distress syndrome is the predominant cause of these deaths. Early continuous positive airway pressure is effective in high-resource settings, reducing the rate of continuous positive airway pressure failure, and the need for mechanical ventilation and surfactant. However, most deaths in preterm infants occur in low-resource settings without access to mechanical ventilation or surfactant. We hypothesize that in such settings, early continuous positive airway pressure will reduce the rate of failure and therefore preterm mortality.MethodsThis is a mixed methods feasibility and acceptability, single-center pilot randomized control trial of early continuous positive airway pressure among infants with birthweight 800–1500 g. There are two parallel arms: (i) application of continuous positive airway pressure; with optional oxygen when indicated; applied in the delivery room within 15 min of birth; transitioning to bubble continuous positive airway pressure after admission to the neonatal unit if Downes Score ≥ 4 (intervention), (ii) supplementary oxygen at delivery when indicated; transitioning to bubble continuous positive airways pressure after admission to the neonatal unit if Downes Score ≥ 4 (control). A two-stage consent process (verbal consent during labor, followed by full written consent within 24 h of birth) and a low-cost third-party allocation process for randomization will be piloted.We will use focus group discussions and key informant interviews to explore the acceptability of the intervention, two-stage consent process, and trial design. We will interview healthcare workers, mothers, and caregivers of preterm infants. Feasibility will be assessed by the proportion of infants randomized within 15 min of delivery; the proportion of infants in the intervention arm receiving CPAP within 15 min of delivery; and the proportion of infants with primary and secondary outcomes measured successfully.DiscussionThis pilot trial will enhance our understanding of methods and techniques that can enable emergency neonatal research to be carried out effectively, affordably, and acceptably in low-resource settings. This mixed-methods approach will allow a comprehensive exploration of parental and healthcare worker perceptions, experiences, and acceptance of the intervention and trial design.Trial registrationThe study is registered on the Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23888.

Integrating the Memory Support Intervention into the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C): can improving memory for treatment in midlife and older adults improve patient outcomes? Study protocol for a randomized controlled trial

BackgroundPoor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments.MethodsParticipants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility.DiscussionThis study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention.Trial registrationClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment

BackgroundUse of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis.MethodsA descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection.ResultsAn ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The ‘ALABAMA unit’ within SystmOne was also created and provided a secure efficient environment to access participants’ EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis.ConclusionsALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs.Trial registrationClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Effect of lycopene on prostate cancer among native African men: A protocol for an open-label randomized clinical trial in Tanzania

Background Prostate cancer (PCa) is the most common cancer and the fifth leading cause of death in men worldwide. The treatment of PCa depends on the clinical stage of the disease, prostate-specific antigen (PSA) level, and histology. Lycopene is a bright red carotenoid found in tomatoes, which enhances apoptosis in prostate cells, but its effectiveness has not been studied in East African countries. This study aimed to determine the effectiveness of lycopene from tomato extracts in reducing PSA levels, disease progression, and apoptosis in the prostate glands of men with PCa in Tanzania. Methods This study will be a randomized phase III clinical trial of men diagnosed with PCa in Tanzania. In total, 400 men will be randomized in a 1:1 ratio to receive intervention (n=200) and control (n=200) and followed for 12 months. The intervention arm will receive tomato paste for daily use in addition to the standard treatment, whereas the control arm will only follow the standard of care. The primary endpoints will be a reduction in PSA levels, improved clinical status, and apoptosis of the prostate gland. Data analysis was performed based on the intention-to-treat principle. Descriptive statistics were used to compare average lycopene and PSA levels in the intervention group using T-test and Chi-squared tests. Generalized linear mixed models will be used to further assess the effect of lycopene on PCa progression, urinary symptoms, and PSA reduction. All statistical tests were two-sided at an alpha level of &lt;0.05. Discussion The study used a food supplement as a drug/intervention with minimal or no adverse reactions. However, there is a fear that the control group may not adhere to the protocol after learning the benefits of tomato paste. The study findings will promote the consumption of tomato paste in males diagnosed with PCa to improve the clinical status and reduce disease progression. Trial registration The study has been registered at the Pan African Clinical Trial Registry with registration No PACTR202405488763956.

Tranexamic Acid During Radical Cystectomy

Among cancer surgeries, patients requiring open radical cystectomy have the highest risk of red blood cell (RBC) transfusion. Prophylactic tranexamic acid (TXA) reduces blood loss during cardiac and orthopedic surgery, and it is possible that similar effects of TXA would be observed during radical cystectomy. To determine whether TXA, administered before incision and for the duration of radical cystectomy, reduced the number of RBC transfusions received by patients up to 30 days after surgery. The Tranexamic Acid During Cystectomy Trial (TACT) was a double-blind, placebo-controlled, randomized clinical trial with enrollment between June 2013 and January 2021. This multicenter trial was conducted in 10 academic centers. A consecutive sample of patients was eligible if the patients had a planned open radical cystectomy for the treatment of bladder cancer. Before incision, patients in the intervention arm received a loading dose of intravenous TXA, 10 mg/kg, followed by a maintenance infusion of 5 mg/kg per hour for the duration of the surgery. In the control arm, patients received indistinguishable matching placebo. The primary outcome was receipt of RBC transfusion up to 30 days after surgery. A total of 386 patients were assessed for eligibility, and 33 did not meet eligibility. Of 353 randomized patients (median [IQR] age, 69 [62-75] years; 263 male [74.5%]), 344 were included in the intention-to-treat analysis. RBC transfusion up to 30 days occurred in 64 of 173 patients (37.0%) in the TXA group and 64 of 171 patients (37.4%) in the placebo group (relative risk, 0.99; 95% CI, 0.83-1.18). There were no differences in secondary outcomes among the TXA group vs placebo group including mean (SD) number of RBC units transfused (0.9 [1.5] U vs 1.1 [1.8] U; P = .43), estimated blood loss (927 [733] mL vs 963 [624] mL; P = .52), intraoperative transfusion (28.3% [49 of 173] vs 24.0% [41 of 171]; P = .08), or venous thromboembolic events (3.5% [6 of 173] vs 2.9% [5 of 171]; P = .57). Non-transfusion-related adverse events were similar between groups. Results of this randomized clinical trial reveal that TXA did not reduce blood transfusion in patients undergoing open radical cystectomy for bladder cancer. Based on this trial, routine use of TXA during open radical cystectomy is not recommended. ClinicalTrials.gov Identifier: NCT01869413.

A randomized controlled trial of a self-guided mobile app targeting repetitive negative thought to prevent depression in university students: study protocol of the Nurture-U Reducing Worry prevention trial

BackgroundTackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.g. worry, rumination) is elevated in university students and is a well-established vulnerability factor for anxiety and depression. Furthermore, there are now evidence-based cognitive-behavioural interventions to tackle RNT. A mobile self-help cognitive-behavioural app targeting RNT, adapted for students may therefore be an effective, scalable, and acceptable way to improve prevention in students.MethodsAn online single blind, two-arm parallel-group Randomised Controlled Trial (RCT) to examine the incidence of major depression and symptoms of anxiety and depression across 12 months in university students aged over 16 who screen into the study with self-reported high levels of worry and/or rumination and no current diagnosis of major depression. Eligible participants will be randomised to the active intervention arm (usual practice plus using a self-guided mobile app targeting RNT) or to the control arm (usual practice). In total, 648 participants aged over 16, with no current major depression, bipolar disorder or psychosis will be recruited from UK universities. Assessments will take place at baseline (pre-randomisation), 3 months and 12 months post- randomisation. Primary endpoint and outcome is incidence of major depression as determined by self-reported diagnostic criteria at 12-month follow-up. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and academic outcomes are secondary outcomes. Compliance, adverse events, and potentially mediating variables will be carefully monitored.DiscussionThe trial aims to provide a better understanding of the causal role of tackling RNT (worry, rumination) using a self-help mobile app with respect to preventing depression in university students. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective mobile-health public health strategies for preventing common mental health problems.Trial registrationhttps://www.isrctn.com/ISRCTN86795807 Date of registration: 27 October 2022

Cluster randomized pilot of the Best Case/Worst Case-Geriatric Oncology (BC/WC-GeriOnc) communication tool for older adults with cancer.

226 Background: BC/WC-GeriOnc is a conversation framework and graphic aid that supports shared decision making (SDM) between oncologists and older adults with cancer. Oncologists are trained to use scenario planning to discuss treatment options by describing the range of plausible outcomes—including an individualized most-likely case—and to make a patient preference-aligned recommendation. Methods: To compare BC/WC-GeriOnc vs enhanced usual care (EUC; usual care plus geriatric assessment), we enrolled 7 medical oncologists from a Comprehensive Cancer Center, Veterans Affairs clinic, and safety-net hospital. For each oncologist, we first enrolled 2 EUC patients age ≥65 with any stage solid tumor and recorded decision-making discussions. Oncologists were then randomized 1:1 to BC/WC-GeriOnc training vs EUC. We enrolled up to 5 additional patients per oncologist and recorded discussions. Patients were followed for 2 months with surveys and a one-on-one semi-structured interview. Primary outcomes were feasibility of patient recruitment/retention and oncologist-reported feasibility of using BC/WC-GeriOnc (surveys and interview). Secondary outcomes were intervention adherence, fidelity, and oncologist- and patient-reported acceptability and appropriateness. Exploratory outcomes included patient-reported SDM, decisional conflict, and regret. We used descriptive statistics to summarize results. Results: Among 43 patients (15 intervention, 28 EUC), median age was 71 (IQR 68-77). The most common cancers were gastrointestinal (30%), thoracic (26%), breast (19%), and genitourinary (19%). Treatment was palliative in 58%. Patient recruitment rate was 70%. Retention was 98% post decision, 93% at 1 month, 86% at 2 months, and 73% at the patient interview. Mean oncologist feasibility, acceptability, and appropriateness scores were each 4 out of 5, which corresponds to “agree.” Intervention adherence (93%) and fidelity were high (median score 14 out of 15, IQR 11-15). Oncologists reported that the tool improved communication: “It really kind of crystalized things in my mind and helped me communicate better.” Patients found that the tool clarified options, encouraged deliberation, and supported oncologist communication. Mean patient-reported SDM score was 85.6 (out of 100-best, SD 15) in the intervention arm and 77.5 (SD 22) in EUC (Cohen’s d 0.43). In the intervention arm, 15% of patients had high decisional conflict after the decision was made (score &gt;37.5/100) versus 21% in EUC. At 2 months, 22% in the intervention arm had high decision regret (score &gt;25/100) compared with 45% in EUC. Conclusions: It was feasible and acceptable for oncologists to use BC/WC-GeriOnc to support SDM for older adults with cancer. Promising patient-reported SDM and decisional outcomes support testing the tool in a full-scale efficacy trial. Clinical trial information: NCT05374304 .

Utilization of genomic tumor testing (GTT) among community oncologists participating in SWOG S2108CD.

320 Background: As targeted therapy options increase in oncology, GTT use is also increasing; however, the strategies and barriers to ordering GTT can vary across clinics. S2108CD is a cluster randomized trial comparing an educationally enhanced genomic tumor board intervention to usual practice to increase evidence-based genome-informed therapy based on GTT results. This analysis seeks to understand the utilization of GTT by physicians in rural and community oncology clinics. Methods: Physicians at sites enrolled on S2108CD completed baseline questionnaires collecting demographics, practice characteristics, and physicians’ experience with and use of GTT in practice. We also conducted semi-structured interviews at baseline and mid-study with select physicians in both arms to understand how and when physicians are ordering GTT and how it guides treatment decision making. Descriptive statistics were generated for survey data. Interviews were analyzed using conventional content analysis to identify recurring themes. Results: Surveys were completed by 117 physicians across 18 Recruitment Centers, with 57 from the usual practice and 60 from the intervention arm. Interviews were conducted with 10 physicians at baseline and 10 within 12-18 months of start of the study. Physicians reported feeling confident in determining whether GTT is clinically appropriate for a patient (42% moderately confident, 50% very confident). Some physicians utilize GTT from multiple vendors, with the following vendors used most frequently: Tempus (50% of physicians), Caris Life Sciences (61%), Foundation Medicine (62%) and Guardant Health (69%). Over two-thirds of physicians reported that professional guidelines were “very important” in the decision to utilize GTT. Reasons for not ordering GTT included “not relevant for the patient” (36%) and “difficulty in obtaining sufficient tissue” (20%) as “often” reasons. Notably, lack of access and cost/insurance coverage were “never” or “rarely” a reason for not ordering GTT in 80% physicians. Long waits to receive GTT results reportedly caused a delay in making patient care decisions (47% sometimes and 26% often). Physicians rely on the following sources to learn about new GTT panels: scientific meetings (91%), peer-reviewed literature (92%), and professional societies (90%). Interview data confirmed that physicians are generally confident ordering GTT but there is variability in the processes for ordering GTT and receipt of GTT results amongst clinics. Conclusions: Physicians enrolled on S2108CD self-reported high genomic confidence in ordering GTT. Access to GTT and coverage of GTT do not appear to be barriers to utilization. However, physicians did report delays in decision-making due to result turn-around times, which were sometimes attributed to length of time to tissue sendout and receipt of results into health record. Funding : NIH/NCI/NCORP grant UG1CA189974. Clinical trial information: NCT05455606 .