Control Arm Research Articles

The Effect of Peer-Mentor Support for Older Vulnerable Patients With Ischemic Heart Disease-A 24-Week Randomized Controlled Trial.

The positive effects of cardiac rehabilitation (CR) are well established; however, among older and vulnerable patients, nonattendance and dropout are prevalent problems. The objective of this study is to explore if a 24-week peer-mentor intervention increases initial and long-term CR attendance. Secondary aims are whether peer-mentor intervention improves lifestyle (diet and physical activity) and psychological outcomes (self-efficacy, anxiety, depression, and quality of life) among older vulnerable patients with ischemic heart disease. The study was designed as a 2-arm, single-center, parallel, 24-week, randomized controlled trial (RCT) with follow-up at 12 and 24 weeks. Patients were randomized at a ratio of 1:1 to receive either the peer-mentor intervention (in addition to standard CR) or standard CR along (control arm). Between August 2021 and March 2023, 117 older, vulnerable patients were enrolled and randomized (59 randomized to peer-mentor intervention and 58 to usual care). The peer-mentor intervention significantly increased CR attendance. This applies to both initial participation in 1 CR session of physical training or dietary advice (78.0% vs 58.6%; P = .03), and long-term attendance in ≥50% dietary advice sessions (50.8% vs 27.6%; P = .01) and completed ≥50% (64.4% vs 41.4% P = .01) or ≥75% of the physical training sessions (59.3% vs 37.9%; P = .02). The study found no statistically significant effect on secondary outcomes. Low CR attendance is a well-known problem, especially among older, vulnerable patients; however, we tested a low-cost, peer-mentor intervention that significantly increased both initial CR participation and long-term attendance in CR sessions in this group of patients.

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.

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.

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...

Does Remdesivir Lower COVID-19 Mortality? A Subgroup Analysis of Hospitalized Adults Receiving Supplemental Oxygen.

The first Adaptive COVID-19 Treatment Trial (ACTT-1) showed that remdesivir improved COVID-19 recovery time compared with placebo in hospitalized adults. The secondary outcome of mortality was almost significant overall (p = 0.07) and highly significant for people receiving supplemental oxygen at enrollment (p = 0.002), suggesting a mortality benefit concentrated in this group. We explore analysis methods that are helpful when a single subgroup benefits from treatment and apply them to ACTT-1, using baseline oxygen use to define subgroups. We consider two questions: (1) is the remdesivir effect for people receiving supplemental oxygen real, and (2) does this effect differ from the overall effect? For Question 1, we apply a Bonferroni adjustment to subgroup-specific hypothesis tests and the Westfall and Young permutation test, which is valid when small cell counts preclude normally distributed test statistics (a frequently unexamined condition in subgroup analyses). For Question 2, we introduce Qmax, the largest standardized difference between subgroup-specific effects and the overall effect. Qmax simultaneously tests whether any subgroup effect differs from the overall effect and identifies the subgroup benefitting most. We demonstrate that Qmax strongly controls the familywise error rate (FWER) when test statistics are normally distributed with no mean-variance relationship. We compare Qmax to a related permutation test, SEAMOS, which was previously proposed but not extensively applied or tested. We show that SEAMOS can have inflated Type 1 error under the global null when control arm event rates differ between subgroups. Our results support a mortality benefit from remdesivir in people receiving supplemental oxygen.

Exposure-response relationships of venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory t(11;14) multiple myeloma patients.

Venetoclax is a first in class BCL-2 inhibitor, currently under investigation for the treatment of t(11;14) multiple myeloma (MM). The objective of this analysis was to characterize the exposure-efficacy and exposure-safety relationships of venetoclax when combined with carfilzomib and dexamethasone (VenKd) in t(11;14)-positive relapsed or refractory (R/R) MM patients from a phase 2 study. Fifty-seven patients receiving VenKd or Kd were included in the analysis. Efficacy endpoints included progression-free survival and clinical response rates of overall response, very good partial response or better and complete response or better. Grade ≥ 3 neutropenia, Grade ≥ 3 infections, Grade ≥ 3 treatment-emergent adverse events and any grade serious treatment-emergent adverse events were evaluated. The analysis demonstrated that adding venetoclax to Kd resulted in increased ORR, ≥VGPR and ≥ CR rates compared to the control arm. Within the venetoclax treatment arms (VenKd), no significant exposure-efficacy relationships were observed for ORR and ≥ VGPR rates. Higher ≥ CR rates trended with higher venetoclax exposures. While both 400mg and 800mg venetoclax in VenKd arms were generally tolerated, higher rates of Grade ≥ 3 neutropenia were observed with higher venetoclax exposures. Higher venetoclax exposures however were not associated with increased rates of Grade ≥ 3 treatment-emergent adverse events, Grade ≥ 3 infections, or serious treatment-emergent adverse events (any grade). These results confirm the benefit of adding venetoclax to carfilzomib and dexamethasone and support continued evaluation of venetoclax 400-800mg once daily in this combination in t(11;14)-positive R/R MM patients. NCT02899052 registered April 18, 2017.

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.

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.

Using the Rehabilitation Treatment Specification System to Describe Experimental and Control Arms of a Clinical Trial for Breast Cancer Survivors

Using the Rehabilitation Treatment Specification System to Describe Experimental and Control Arms of a Clinical Trial for Breast Cancer Survivors

Effectiveness of a Digital Health Intervention Leveraging Reinforcement Learning: Results From the Diabetes and Mental Health Adaptive Notification Tracking and Evaluation (DIAMANTE) Randomized Clinical Trial.

Digital and mobile health interventions using personalization via reinforcement learning algorithms have the potential to reach large number of people to support physical activity and help manage diabetes and depression in daily life. The Diabetes and Mental Health Adaptive Notification and Tracking Evaluation (DIAMANTE) study tested whether a digital physical activity intervention using personalized text messaging via reinforcement learning algorithms could increase step counts in a diverse, multilingual sample of people with diabetes and depression symptoms. From January 2020 to June 2022, participants were recruited from 4 San Francisco, California-based public primary care clinics and through web-based platforms to participate in the 24-week randomized controlled trial. Eligibility criteria included English or Spanish language preference and a documented diagnosis of diabetes and elevated depression symptoms. The trial had 3 arms: a Control group receiving a weekly mood monitoring message, a Random messaging group receiving randomly selected feedback and motivational text messages daily, and an Adaptive messaging group receiving text messages selected by a reinforcement learning algorithm daily. Randomization was performed with a 1:1:1 allocation. The primary outcome, changes in daily step counts, was passively collected via a mobile app. The primary analysis assessed changes in daily step count using a linear mixed-effects model. An a priori subanalysis compared the primary step count outcome within recruitment samples. In total, 168 participants were analyzed, including those with 24% (40/168) Spanish language preference and 37.5% (63/168) from clinic-based recruitment. The results of the linear mixed-effects model indicated that participants in the Adaptive arm cumulatively gained an average of 3.6 steps each day (95% CI 2.45-4.78; P<.001) over the 24-week intervention (average of 608 total steps), whereas both the Control and Random arm participants had significantly decreased rates of change. Postintervention estimates suggest that participants in the Adaptive messaging arm showed a significant step count increase of 19% (606/3197; P<.001), in contrast to 1.6% (59/3698) and 3.9% (136/3480) step count increase in the Random and Control arms, respectively. Intervention effectiveness differences were observed between participants recruited from the San Francisco clinics and those recruited via web-based platforms, with the significant step count trend persisting across both samples for participants in the Adaptive group. Our study supports the use of reinforcement learning algorithms for personalizing text messaging interventions to increase physical activity in a diverse sample of people with diabetes and depression. It is the first to test this approach in a large, diverse, and multilingual sample. ClinicalTrials.gov NCT03490253; https://clinicaltrials.gov/study/NCT03490253. RR2-10.1136/bmjopen-2019-034723.

A Koopman-based residual modeling approach for the control of a soft robot arm

Soft robots are challenging to model and control due to their poorly defined kinematics and nonlinear dynamics. Recently, Koopman operator theory has been shown capable of constructing control-oriented soft robot models from data. However, building these models requires extensive data collection and they do not necessarily generalize well outside of the training observations. This paper presents a more data-efficient and generalizable approach to soft robot modeling that first identifies a physics-based Koopman model then supplements it with a data-driven residual Koopman model. The resulting combined model is linear and thus compatible with real-time model-based control techniques such as Model Predictive Control (MPC). The efficacy of the approach is demonstrated on several simulated systems and on a real soft robot arm, where it is shown to generate models that are more accurate than purely physics-based models and require less data to construct than purely data-driven models. Using a model-based controller, the soft arm is able to successfully track end effector trajectories, perform a pick-and-place task, and write on a dry-erase board, showcasing the applicability of this framework to increase the capabilities of soft robotic systems.

Efficacy and safety of a lipid-containing artificial tear compared with a non-lipid containing tear: a randomized clinical trial.

Dry eye disease (DED) is a prevalent condition affecting over 16 million patients in the USA. DED and the symptoms of ocular discomfort are debilitating and a significant burden on patients. If left untreated, DED can progress to cause severe pathology. Treatment is often initiated by patients without consulting a healthcare professional. This study investigated the safety and efficacy of a novel lipid-containing eye drop (BTC), which might better mimic the components of natural tears. This was a multicenter, randomized, double-masked, active control, two arm, parallel group study of eye drops in adult subjects with self-reported DED. Subjects were randomly assigned to BTC or control (commercially available non-lipid eye drops; NLED) arm and were followed for 30 days. Assessments using visual analog scale and patient-reported outcomes (PRO) questionnaires, non-invasive tear break up time, slit-lamp examination, and subject-reported ocular symptoms were conducted at baseline and at days 7 and 30. The primary endpoint was change in overall ocular comfort score from baseline to day 30. 158 subjects were randomized, of whom 130 completed the study per protocol (PP). Mean (SD) age was 47.8 (14.14) years. The mean (95% CI) change in overall comfort scores at the 30-day follow-up in the PP population was 21.4 (15.1, 27.7) for the test drop and 10.0 (3.9, 16.1) for the comparator. The mean (95% CI) treatment difference was 11.3 (2.6, 20.1); this met the pre-defined requirements for non-inferiority. There was no significant difference in the proportion of eyes with reported ocular symptoms between the groups. At day 7, the OR (95% CI) was 0.967 (0.528, 1.770) and at day 30 was 1.160 (0.610, 2.203). There were no Grade 3 or higher corneal edema, corneal neovascularization, corneal staining, conjunctival injection, tarsal abnormalities or any other biomicroscopy findings, and no corneal infiltrates observed during the study. The investigational lipid eye drop BTC was noninferior to the commercially available non-lipid comparator in all parameters measured and has the potential to provide an effective therapy for subjects with symptoms of dry eye who would benefit from a lipid-based artificial tear. NCT03995355 ( http://www. gov ), registered June 24, 2019.

Deadlocked International Institutions: Implications for Negotiated Conflict Management

Abstract This article argues that the international institutions in which negotiations have often taken place have been challenged by increased conflict among member states in the early 21st century. Multilateral international institutions function best when common interests are viewed as paramount by the state parties, because they allow the state parties to negotiate structures and processes that serve their shared interests and values. The paper analyzes the difficulties in managing international conflicts in the UN, osce, nato, and EU since 2000 due in part to the inability to achieve consensus within fractured and stalemated institutions. These problems have increasingly limited the role of these institutions in managing some of the most dangerous global conflicts, including on arms control and disarmament and managing the Russian war in Ukraine.

Rapid-Learning Collaborative Pushing and Grasping via Deep Reinforcement Learning and Image Masking

When multiple objects are positioned close together or stacked, pre-grasp operations such as pushing objects can be used to create space for the grasp, thereby improving the grasping success rate. This study develops a model based on a deep Q-learning network architecture and introduces a fully convolutional network to accurately identify pixels in the workspace image that correspond to target locations for exploration. In addition, this study incorporates image masking to limit the exploration area of the robotic arm, ensuring that the agent consistently explores regions containing objects. This approach effectively addresses the sparse reward problem and improves the convergence rate of the model. Experimental results from both simulated and real-world environments show that the proposed method accelerates the learning of effective grasping strategies. When image masking is applied, the success rate in the grasping task reaches 80% after 600 iterations. The time required to reach 80% success rate is 25% shorter when image masking is used compared to when it is not used. The main finding of this study is the direct integration of image masking technique with a deep reinforcement learning (DRL) algorithm, which offers significant advancement in robotic arm control. Furthermore, this study shows that image masking technique can substantially reduce training time and improve the object grasping success rate. This innovation enables the robotic arm to better adapt to scenarios that conventional DRL methods cannot handle, thereby improving training efficiency and performance in complex and dynamic industrial applications.

8613 Diabetes remission: experience from a randomized control trial conducted in a tertiary care hospital in India

Abstract Disclosure: A.M. Chakraborty: None. R. Waila: None. S. Bhansali: None. H. Bhujade: None. N. Sachdeva: None. S. Bhadada: None. Introduction: The usual perception and interpretation of diabetes mellitus is that of an irreversible and chronic persistent disease with little scope for remission. Following the success of metabolic surgery and intensive lifestyle modification, it is time for pharmacotherapy to sept in. Methodology: It was a single-center, randomized controlled trial conducted in patients having HbA1c below 9 % at randomization and having a duration of diabetes less than 2 years. Patients with organ-threatening chronic diseases and severe diabetes-related complications have been excluded. Study populations have been randomized to 1:1 to receive pharmacotherapy with oral semaglutide, dapagliflozin, and metformin in one arm and vildagliptin, metformin, and titrated glimepiride in the control arm. Duration of therapy was 6 months including 2 months of up titration of semaglutide. Patients have been followed up for 3 months after stopping all therapy following 6 months of therapy. The primary outcome was to find out the remission rates in patients with Type 2 diabetes mellitus treated with a combination of oral Semaglutide and dapagliflozin on top of metformin monotherapy and to compare with the standard diabetes practice. The secondary outcome was to assess the anthropometric change and change in beta cell function parameters with a mixed meal tolerance test. Results: A total of 38 patients have completed therapy, 17 were in the trial arm and 21 in the control arm. Among 17 patients in the trial arm, all the patients were in remission as per the prespecified criteria. Among the patients who completed 6 months of follow-up (n-13), 11 patients (84%) maintained remission in the trial arm. The remission rate was 100% in the trial arm and 48% in the conventional arm (p&amp;lt;0.001) after 3 months and 84% and 27.7% in the trial arm and conventional arm respectively after 6 months of follow-up (p&amp;lt;0.05). Reduction in BMI (p &amp;lt;0.001) and percent body fat (p&amp;lt;0.01) and increase in disposition index after mixed meal tolerance test (p&amp;lt;0.01) was statistically related to remission. Conclusion: Remission of diabetes as defined by ADA in the consensus statement (HbA1c &amp;lt; 6.5 % without glucose-lowering therapy for at least 3 months) is a reality. It can be achieved by pharmacotherapy targeting body weight and adiposity. The main predictors of remission were a reduction of BMI and body fat and an increased disposition Index. Since it is an ongoing study, further follow-up is planned to determine the continuation of the remission phase among those who achieved remission with pharmacotherapy. Presentation: 6/3/2024

8046 Milk Provision as a Potential Intervention to Improve Iodine Status in a Pregnant Cohort in Northern Ireland (NI), UK: A Randomised Controlled Trial

Abstract Disclosure: L.R. Kayes: None. K.R. Mullan: None. J.V. Woodside: None. Iodine deficiency is the leading cause of reversible mental retardation worldwide. During pregnancy there is ∼50% increase in iodine requirement for foetal neurodevelopment. The most recently studied cohorts of pregnant women across Ireland and UK consistently demonstrated mild iodine deficiency (target median urinary iodine concentration (mUIC) ≥150 µg/L). A recent study in NI has shown that women of child-bearing age provided with three litres of cow’s milk per week had improved iodine status. We wished to explore whether a similar milk intervention might improve iodine status during pregnancy. Pregnant women were recruited at their first antenatal appointment, and all were provided with the British Dietetic Association’s iodine food fact sheet. Participants were randomised to either milk intervention, (four litres/week milk delivered weekly free of charge), or no milk delivery (control group). Patients were stratified based on use of an iodine-containing multivitamin prior to randomisation. Urine was collected at recruitment, after 12-week intervention period, in the third trimester and 6-12 weeks postnatally along with an infant urine sample when possible. A total of 55 urine samples were collected from infants. A total of 118 women were recruited. Participants had a mean age of 32 years, (range 21 - 45) with a mean BMI of 27.5 kg/m2. Mean gestational age was 12 weeks (IQR 12-13 weeks). The mUIC in the whole group women was 53.2 µg/L in the first trimester. In the control group the mUIC at the first study visit (n=59) was 93.4 µg/L (22% achieving iodine sufficiency); at the second visit (n=38), the mUIC was 158.7 µg/L with 34% achieving sufficiency. In the milk group the mUIC at the first study visit (n=59) was 82.0 µg/L with 10% achieving sufficiency (no statistical significance between groups, p=0.08); at the second visit (n=43), mUIC was 154.7 µg/L with 37% achieving sufficiency (no statistical difference between groups p=0.78). The mean change in UIC between the first and second trimesters was 44.5 and 88.1 µg/L in the control and milk arms respectively (p=0.27). In this cohort, 71.4% of women reported taking an iodine-containing multivitamin in the first trimester of pregnancy with no difference between group randomised to milk intervention (p=0.95). In the infants, mUIC was 124.1 µg/L with no statistically difference in the proportion reaching iodine sufficiency according to maternal randomisation (p=0.64) or maternal use of an iodine-containing multivitamin (p=0.95). In this cohort, there was no significant improvement in mUIC in those receiving a milk intervention. Presentation: 6/1/2024

8046 Milk Provision as a Potential Intervention to Improve Iodine Status in a Pregnant Cohort in Northern Ireland (NI), UK: A Randomised Controlled Trial

Abstract Disclosure: L.R. Kayes: None. K.R. Mullan: None. J.V. Woodside: None. Iodine deficiency is the leading cause of reversible mental retardation worldwide. During pregnancy there is ∼50% increase in iodine requirement for foetal neurodevelopment. The most recently studied cohorts of pregnant women across Ireland and UK consistently demonstrated mild iodine deficiency (target median urinary iodine concentration (mUIC) ≥150 µg/L). A recent study in NI has shown that women of child-bearing age provided with three litres of cow’s milk per week had improved iodine status. We wished to explore whether a similar milk intervention might improve iodine status during pregnancy. Pregnant women were recruited at their first antenatal appointment, and all were provided with the British Dietetic Association’s iodine food fact sheet. Participants were randomised to either milk intervention, (four litres/week milk delivered weekly free of charge), or no milk delivery (control group). Patients were stratified based on use of an iodine-containing multivitamin prior to randomisation. Urine was collected at recruitment, after 12-week intervention period, in the third trimester and 6-12 weeks postnatally along with an infant urine sample when possible. A total of 55 urine samples were collected from infants. A total of 118 women were recruited. Participants had a mean age of 32 years, (range 21 - 45) with a mean BMI of 27.5 kg/m2. Mean gestational age was 12 weeks (IQR 12-13 weeks). The mUIC in the whole group women was 53.2 µg/L in the first trimester. In the control group the mUIC at the first study visit (n=59) was 93.4 µg/L (22% achieving iodine sufficiency); at the second visit (n=38), the mUIC was 158.7 µg/L with 34% achieving sufficiency. In the milk group the mUIC at the first study visit (n=59) was 82.0 µg/L with 10% achieving sufficiency (no statistical significance between groups, p=0.08); at the second visit (n=43), mUIC was 154.7 µg/L with 37% achieving sufficiency (no statistical difference between groups p=0.78). The mean change in UIC between the first and second trimesters was 44.5 and 88.1 µg/L in the control and milk arms respectively (p=0.27). In this cohort, 71.4% of women reported taking an iodine-containing multivitamin in the first trimester of pregnancy with no difference between group randomised to milk intervention (p=0.95). In the infants, mUIC was 124.1 µg/L with no statistically difference in the proportion reaching iodine sufficiency according to maternal randomisation (p=0.64) or maternal use of an iodine-containing multivitamin (p=0.95). In this cohort, there was no significant improvement in mUIC in those receiving a milk intervention. Presentation: 6/1/2024

In vivo anti-schistosomal activity of the methanol extracts from Searsia longipes and Lannea schimperi

Schistosomiasis is a disease caused by the flat worms under the genus Schistosoma. The disease is prominent in tropical and sub tropical countries and it is manifested in two forms; the acute and the chronic form. Treatment and control of the schistosomiasis is constrained with various factors including immerging worm resistance and selective efficacy of the current recommended drug of choice. This therefore calls for the search of new approaches to offset the problems. The aim of this study was to investigate the efficacy of the methanolic extract from Searsia longipes and Lannea schimperi against Schistosoma mansoni by using animal model. Swiss albino mice were used for the efficacy testing, whereby, for each extract, 5 groups of mice were used, and each contained 5 mice. Three different doses were administered to three groups, whereas the remaining two groups were used as negative and positive control arms. Efficacies were assessed based on the reduction of the worm eggs in the faeces and organs, body weight gain, loss of liver weight, as well as reduction of worm burden. Both extracts demonstrated significant egg and worm reduction, which was directly proportional to the dose increment. At the highest dose used, Searsia longipes expressed the higher percentage egg reduction (73.33 %), whereas Lannea schimperi demonstrated the higher worm burden reduction (68.53 %). The present study provides strong evidence of the anti-schistosomal activity of the extracts from both S. longipes and L. schimperi. These findings are a significant step forward, suggesting that these plants could be a promising alternative medicine for the treatment of schistosomiasis. However, further investigations are warranted to isolate the compound responsible for this activity and to assess the sub-acute toxicity of the plant extracts. This next phase of research is crucial for advancing our understanding and potential use of these plant extracts.

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.