Treatment Allocation Research Articles

Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming.

Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 12, and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety, and other behavioral features. Mice treated with vehicle (n = 18) manifested a 118.71 ± 95.96% increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60 ± 17.90% in mice treated with psilocybin (n = 16) and by 19.20 ± 20.05% in mice treated with psychedelic mushroom extract (n = 16) (p = 0.001 for effect of time; p = 0.0001 for time × treatment interaction). Five mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n = 12) and psychedelic mushroom extract (n = 13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study. Prepared with BioRender ( https://www.biorender.com/ ).

Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial.

Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis. SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete. Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Effects on serum glucose and cortisol concentrations were minimal and transient. There were no treatment-emergent deaths or treatment-related serious adverse events. Plasma concentrations of fluticasone propionate showed a blunted initial peak with terminal half-life of approximately 18-20 weeks. These phase 2 results suggest that EP-104IAR has the potential to offer clinically meaningful pain relief in knee osteoarthritis for an extended period of up to 14 weeks, longer than published data for currently marketed corticosteroids. There were minimal effects on glucose and cortisol, and stable fluticasone propionate concentrations in plasma. The safety and efficacy of EP-104IAR will be further evaluated in phase 3 trials, including the possibility of bilateral and repeat dosing with EP-104IAR. Eupraxia Pharmaceuticals. For the Danish translation of the abstract see Supplementary Materials section.

Artificial Intelligence for Optimizing Cancer Imaging: User Experience Study.

The need for increased clinical efficacy and efficiency has been the main force in developing artificial intelligence (AI) tools in medical imaging. The INCISIVE project is a European Union-funded initiative aiming to revolutionize cancer imaging methods using AI technology. It seeks to address limitations in imaging techniques by developing an AI-based toolbox that improves accuracy, specificity, sensitivity, interpretability, and cost-effectiveness. To ensure the successful implementation of the INCISIVE AI service, a study was conducted to understand the needs, challenges, and expectations of health care professionals (HCPs) regarding the proposed toolbox and any potential implementation barriers. A mixed methods study consisting of 2 phases was conducted. Phase 1 involved user experience (UX) design workshops with users of the INCISIVE AI toolbox. Phase 2 involved a Delphi study conducted through a series of sequential questionnaires. To recruit, a purposive sampling strategy based on the project's consortium network was used. In total, 16 HCPs from Serbia, Italy, Greece, Cyprus, Spain, and the United Kingdom participated in the UX design workshops and 12 completed the Delphi study. Descriptive statistics were performed using SPSS (IBM Corp), enabling the calculation of mean rank scores of the Delphi study's lists. The qualitative data collected via the UX design workshops was analyzed using NVivo (version 12; Lumivero) software. The workshops facilitated brainstorming and identification of the INCISIVE AI toolbox's desired features and implementation barriers. Subsequently, the Delphi study was instrumental in ranking these features, showing a strong consensus among HCPs (W=0.741, P<.001). Additionally, this study also identified implementation barriers, revealing a strong consensus among HCPs (W=0.705, P<.001). Key findings indicated that the INCISIVE AI toolbox could assist in areas such as misdiagnosis, overdiagnosis, delays in diagnosis, detection of minor lesions, decision-making in disagreement, treatment allocation, disease prognosis, prediction, treatment response prediction, and care integration throughout the patient journey. Limited resources, lack of organizational and managerial support, and data entry variability were some of the identified barriers. HCPs also had an explicit interest in AI explainability, desiring feature relevance explanations or a combination of feature relevance and visual explanations within the toolbox. The results provide a thorough examination of the INCISIVE AI toolbox's design elements as required by the end users and potential barriers to its implementation, thus guiding the design and implementation of the INCISIVE technology. The outcome offers information about the degree of AI explainability required of the INCISIVE AI toolbox across the three services: (1) initial diagnosis; (2) disease staging, differentiation, and characterization; and (3) treatment and follow-up indicated for the toolbox. By considering the perspective of end users, INCISIVE aims to develop a solution that effectively meets their needs and drives adoption.

Detection of genomic alterations in liquid biopsies from patients with non-small cell lung cancer using FoundationOne Liquid CDx: a cost-effectiveness analysis

Objective Liquid biopsy (LB) is a non-invasive technique to detect genetic alterations by next-generation sequencing (NGS) when tissue biopsy is not available. This study aims to estimate in the Spanish setting, the cost-effectiveness of using FoundationOne Liquid CDx (F1L CDx), a novel blood-derived LB test based on NGS, versus non-molecular diagnosis (non-mDx) in patients with advanced non-small cell lung cancer (NSCLC) in whom tissue sampling is not feasible. Methods A joint model was developed combining a decision-tree with partitioned survival models to calculate the costs and health outcomes over a lifetime horizon, comparing F1L CDx in LB versus non-mDx. Only direct costs (expressed in €of 2023) were included and a 3% discount rate for future costs and effects was considered. Health outcomes were expressed in Life Years (LYs) and Quality-Adjusted Life Years (QALYs). Utilities and treatment efficacy were obtained from the literature. An expert panel of 11 Spanish oncologists determined the treatment allocation and validated all model inputs and assumptions. Several sensitivity analyses were performed to assess the robustness of the results. Results In a hypothetical cohort of 1,000 patients, LB using F1L CDx would detect 386 alterations, so those patients could be treated with targeted therapies or enrolled in clinical trials. Cost-effectiveness results showed that F1L CDx provides greater effectiveness than non-mDx (+383.95 LYs and +305.94 QALYs), with an additional cost of €2,898,308. The incremental cost-utility ratio was €9,473/QALY gained. The probabilistic sensitivity analysis confirmed the robustness of the cost-effectiveness results. Limitations Various limitations inherent to cost-effectiveness analyses were described. Conclusion LB with F1L CDx test is a cost-effective strategy in Spain for patients with advanced NSCLC without tissue sample available for molecular diagnosis, improving the personalized treatment of these patients.

Physical Activity in Mild Vascular Cognitive Impairment: Results of the AFIVASC Randomized Controlled Trial at 6 Months.

Vascular cognitive impairment is frequent, in mild (mVCI) or severe forms (vascular dementia). To do a randomized controlled-trial to evaluate the impact of physical activity on cognition (primary outcome), neurocognitive measures, quality of life, functional status, and physical function (secondary outcomes), in patients with mVCI. A hundred and four patients with mVCI (mean age 71.2 years; 53 women) were randomized for a six-month intervention of moderate physical activity (60-minute sessions, 3 times/week) (n = 53) or best-practice "usual care" (n = 51). Comprehensive evaluations of primary and secondary outcomes included an objective measure of physical activity through accelerometry at baseline and after intervention. Mean session attendance was 58%. Adverse events were negligible. After 6 months, no significant primary outcome change was observed, either in the intervention or 'usual care' group. The intervention group improved significantly in some secondary outcomes in physical function - aerobic capacity (U = 403; p = 0.000) and agility (U = 453; p = 0.005) after 6 months. Regardless of randomization arm, a post-hoc analysis based on fulfilling at least 21.5 minutes/day of moderate or 10.7 minutes/day of vigorous physical activity (World Health Organization-WHO standards) revealed improvements. These were not only in motor capacity but also on the global measure of cognition, executive functions and memory. Physical activity was safe and beneficial regarding domains of physical function. No significant cognitive decline was registered over 6-months, regardless of intervention allocation. Larger samples, longer follow-ups and focus on intervention adherence are needed to fully analyze the impact of WHO recommendations for physical activity in mVCI populations.

Maladaptive eating behaviors and health-related quality of life in Spanish children

In children, assessing health-related quality of life (HRQoL) and identifying the factors that can influence it are essential to understanding their overall health and well-being. Although eating disorders in children have been associated with reduced HRQoL, the impact of maladaptive eating behaviors, such as external eating, emotional eating and restrained eating, on children's HRQoL has not yet been prospectively explored. Therefore, the aim of this study was to determine whether external, emotional and restrained eating at baseline was associated with HRQoL in children after 14.65 months (95% CI: 14.57–14.73) of follow-up. The study involved 690 boys and 681 girls aged between 8 and 10 years, recruited from primary schools in Catalonia (Spain). To assess the relationship between external, emotional and restrained eating behaviors at baseline and HRQoL at follow-up, the Dutch Eating Behavior and KIDSCREEN-10 questionnaires were used, respectively. After adjusting for sex, age, intervention allocation group, school, maternal education, zBMI and physical activity, external and emotional eating behaviors at baseline were negatively associated with HRQoL at follow-up (p < 0.01). These associations were attenuated after final adjustment for HRQoL at baseline. Furthermore, a composite score of maladaptive eating behaviors at baseline was created by summing the individual scores for emotional, restrained and external eating behaviors. This composite score showed a significant inverse association with HRQoL at follow-up, even after adjusting for baseline HRQoL (p = 0.024). In conclusion, external and emotional eating behaviors seems to negatively affect HRQoL prospectively in Spanish children. The composite score of maladaptive eating behaviors showed a stronger inverse association with HRQoL than each eating behavior individually. Trial registration numberISRCTN registry: ISRCTN68403446; Date of registration, August 01, 2014 ′Retrospectively registered'.

Policy Learning for Many Outcomes of Interest: Combining Optimal Policy Trees with Multi-objective Bayesian Optimisation

AbstractMethods for learning optimal policies use causal machine learning models to create human-interpretable rules for making choices around the allocation of different policy interventions. However, in realistic policy-making contexts, decision-makers often care about trade-offs between outcomes, not just single-mindedly maximising utility for one outcome. This paper proposes an approach termed Multi-Objective Policy Learning (MOPoL) which combines optimal decision trees for policy learning with a multi-objective Bayesian optimisation approach to explore the trade-off between multiple outcomes. It does this by building a Pareto frontier of non-dominated models for different hyperparameter settings which govern outcome weighting. The method is applied to a real-world case-study of pricing targetting subsididies for anti-malarial medication in Kenya.

A Group Parenting Intervention for Male Postpartum Depression

Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings. To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual. This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022. LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months. The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization. Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months. The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted. ClinicalTrials.gov Identifier: NCT03564847.

Efficacy and safety of ketogenic diet in infants with epilepsy: KIWE RCT

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with &gt; 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Comparison of pooled cohort equation and PREVENT™ risk calculator for statin treatment allocation

Comparison of pooled cohort equation and PREVENT™ risk calculator for statin treatment allocation

The effect of rituximab on patient reported outcomes in the preclinical phase of rheumatoid arthritis: 2 year data from the PRAIRI study

ObjectivesEarly treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and...

Effect of the i2TransHealth e-health intervention on psychological distress among transgender and gender diverse adults from remote areas in Germany: a randomised controlled trial

Transgender and gender diverse (TGD) people in remote areas face challenges accessing health-care services, including mental health care and gender-affirming medical treatment, which can be associated with psychological distress. In this study, we aimed to evaluate the effectiveness of a 4-month TGD-informed e-health intervention to improve psychological distress among TGD people from remote areas in northern Germany. In a randomised controlled trial done at a single centre in Germany, adults (aged ≥18 years) who met criteria for gender incongruence or gender dysphoria and who lived at least 50 km outside of Hamburg in one of the northern German federal states were recruited and randomly assigned (1:1) to i2TransHealth intervention or a wait list control group. Randomisation was performed with the use of a computer-based code. Due to the nature of the intervention, study participants and clinical staff were aware of treatment allocation, but researchers responsible for data analysis were masked to allocation groups. Study participants in the intervention group (service users) started the i2TransHealth intervention immediately after completing the baseline survey after enrolment. Participants assigned to the control group waited 4 months before they were able to access i2TransHealth services or regular care. The primary outcome was difference in the Brief Symptom Inventory (BSI)-18 summary score between baseline and 4 months, assessed using a linear model analysis. The primary outcome was assessed in the intention-to-treat (ITT) population, which included all randomly assigned participants. The trial was registered with ClinicalTrials.gov, NCT04290286. Between May 12, 2020, and May 2, 2022, 177 TGD people were assessed for eligibility, of whom 174 were included in the ITT population (n=90 in the intervention group, n=84 in the control group). Six participants did not provide data for the primary outcome at 4 months, and thus 168 people were included in the analysis population (88 participants in the intervention group and 80 participants in the control group). At 4 months, in the intervention group, the adjusted mean change in BSI-18 from baseline was -0·65 (95% CI -2·25 to 0·96; p=0·43) compared with 2·34 (0·65 to 4·02; p=0·0069) in the control group. Linear model analysis identified a significant difference at 4 months between the groups with regard to change in BSI-18 summary scores from baseline (between-group difference -2·98 [95% CI -5·31 to -0·65]; p=0·012). Adverse events were rare: there were two suicide attempts and one participant was admitted to hospital in the intervention group, and in the control group, there was one case of self-harm and one case of self-harm followed by hospital admission. The intervention was clinically significant in averting worsening psychological distress in service users, outperforming the wait list control group. These findings support the effectiveness of e-health services in TGD health care, specifically for people from remote areas. Innovation Committee at the Federal Joint Committee. For the German translation of the abstract see Supplementary Materials section.

Gestational diabetes mellitus - Neonatal and maternal outcomes in women treated with insulin or diet: A propensity matched analysis

AimsPregnant women worldwide face the risk of developing gestational diabetes mellitus (GDM), if left untreated, can cause complications. The study explores factors influencing the choice between diet control and insulin therapy for pregnant women with GDM. It aims to understand how these choices impact maternal and neonatal outcomes. MethodsIn this quasi-experimental study, clinicians determined treatment (diet control or insulin) for 1030 individuals with GDM at a private practice from 2010 to 2020 based on baseline characteristics. Propensity scores (PS), reflecting the probability of treatment allocation, were derived through multiple logistic regression. ResultsAfter PS matching, 386 individuals were paired from two study groups. The insulin-treated group exhibited a 4.43 times higher risk of neonatal hypoglycemia than the diet group. Insulin-treated individuals, stratified by PS, revealed that the high-risk quartile had significantly higher mean insulin requirements and a doubled dose at full term compared to the lower-risk quartiles. The mean insulin dose did not significantly differ in the first three quartiles, but the last quartile showed a significant increase (p = 0.008), particularly for individuals with PS exceeding 0.70, indicating a higher insulin dose requirement for effective glucose control. ConclusionThis study reveals that individuals with a bad obstetrics history, a family history of diabetes, obesity, and elevated baseline glycemic parameters necessitate higher insulin doses. This insight improves clinicians' decision-making in diagnosis and treatment planning, enhancing the precision of medical practices.

Indocyanine Green and Hepatobiliary Surgery: An Overview of the Current Literature.

Indocyanine green (ICG) is an inert polypeptide that almost totally binds to high molecular weight plasma proteins; it is cleared by the hepatocytes and directly excreted into the bile with a half-life of about 3-5 minutes. Specific systems are required to see fluorescent images. The use of this dye has been reported in different surgical specialties, and the applications in hepatobiliary surgery are widening. Being firstly used to evaluate the preoperative liver function, intra- and postoperative dynamic checking of hepatic activity has been reported and integrated within perioperative protocols allowing a tailored treatment allocation. Intravenous injection (IV) or injection into the gallbladder can ease difficult cholecystectomy. Biliary leakage detection could be enhanced by IV ICG injection. Although with some contrasting results, the use of ICG for both delineating the limits of the resection and tumor-enhanced visualization was demonstrated to improve short- and long-term outcomes. Although the lack of strong evidence still precludes the introduction of this tool in clinical practice, it harbors great potential in liver surgery.

Combined interventions for the testing and treatment of HIV and schistosomiasis among fishermen in Malawi: a three-arm, cluster-randomised trial

Undiagnosed HIV and schistosomiasis are highly prevalent among fishermen in the African Great Lakes region. We aimed to evaluate the efficacy of lakeside interventions integrating services for HIV and male genital schistosomiasis on the prevalence of schistosomiasis, uptake of antiretroviral therapy (ART) for HIV, and voluntary male medical circumcision (VMMC) among fishermen in Malawi. We conducted a three-arm, cluster-randomised trial in 45 lakeshore fishing communities (clusters) in Mangochi, Malawi. Clusters were defined geographically by their home community as the place where fishermen leave their boats (ie, a landing site). Eligible participants were male fishermen (aged ≥18 years) who resided in a cluster. Clusters were randomly allocated (1:1:1) through computer-generated random numbers to either enhanced standard of care (SOC), which offered invitation with information leaflets to a beach clinic offering HIV testing and referral, and presumptive treatment for schistosomiasis with praziquantel; peer education (PE), in which a nominated fisherman was responsible for explaining the study leaflet to promote services to his boat crew; or peer distribution education (PDE), in which the peer educator explained the leaflet and distributed HIV self-test kits to his boat crew. The beach clinic team and fishermen were not masked to intervention allocation; however, investigators were masked until the final analysis. Coprimary composite outcomes were the proportion of participants who had at least one Schistosoma haematobium egg observed on light microscopy from 10 mL of urine filtrate and the proportion who had self-reported initiating ART or scheduling VMMC by day 28. Outcomes were analysed by intention to treat; multiple imputation for missing outcomes was done; random-effect binomial models adjusting for baseline imbalance and clustering were used to compute unadjusted and adjusted risk differences, risk ratios (RRs) and 95% CIs, and intracluster correlation coefficients for each outcome. This trial is registered with ISRCTN, ISRCTN14354324. Between March 1, 2022, and Jan 29, 2023, 45 (65·2%) of 69 clusters assessed for eligibility were enrolled in the trial, with 15 clusters per arm. Of the 6036 fishermen screened at baseline, 5207 (86·3%) were eligible for participation: 1745 (87·6%) of 1991 in the enhanced SOC group, 1687 (81·9%) of 2061 in the PE group, and 1775 (89·5%) of 1984 in the PDE group. Compared with the prevalence of active schistosomiasis in the enhanced SOC group (292 [16·7%] of 1745), 241 (13·6%) of 1775 fishermen in the PDE group (adjusted RR 0·80 [95% CI 0·69-0·94]; p=0·0054) and 263 (15·6%) of 1687 fishermen in the PE group (0·92 [0·79-1·07]; p=0·28) had schistosomiasis at day 28. 230 (13·2%) in the enhanced SOC group, 281 (16·7%) in the PE group, and 215 (12·1%) in the PDE group initiated ART or were scheduled for VMMC. ART initiation or VMMC scheduling was not significantly increased with the PDE intervention (0·88 [0·74-1·05); p=0·15) and was marginally increased with the PE intervention (1·16 [0·99-1·37]; p=0·069) when compared with the enhanced SOC group. No serious adverse events were reported in this trial. We found weak evidence for the use of peer education to increase uptake of ART and VMMC, but strong evidence for the added distribution of HIV self-test kits to promote high engagement with services and reduce the prevalence of active schistosomiasis, suggesting a high potential for scale-up in hard-to-reach communities across Malawi. Wellcome Trust and the UK National Institute for Health Research.

Mobile health clinics for distribution of vaccinations to underserved communities during health emergencies: A COVID-19 case study

ObjectivesMobile health clinics (MHCs) effectively provide healthcare to underserved communities. However, their application during health emergencies is understudied. We described the implementation of an MHC program delivering vaccinations during the COVID-19 pandemic, examined the program's reach to medically underserved communities, and investigated characteristics of vaccination uptake in order to inform the utility of MHCs during health emergencies. Study designThe study observed COVID-19 MHC vaccination rates and factors associated with uptake between February 20th, 2021, and February 17th, 2022. MethodsPrisma Health deployed six MHCs to underserved communities. We described the characteristics of individuals who utilized the MHCs and evaluated census tract-level community factors associated with use of the MHCs through generalized linear mixed effects models. ResultsThe MHCs conducted 260 visits at 149 unique sites in South Carolina, providing 12,102 vaccine doses to 8545 individuals: 2890 received a partial dose, 4355 received a primary series, and 1300 received a booster dose. Among individuals utilizing the MHC, the median age was 42 years (IQR: 22–58), 44.0 % were Black, 49.2 % were male, and 44.2 % were uninsured. Black, Hispanic, and uninsured individuals were significantly more likely to utilize MHC services for COVID-19 vaccination. During periods when vaccines were limited, MHC utilization was significantly greater in communities facing access barriers to healthcare. ConclusionsThe high COVID-19 vaccination uptake at MHCs demonstrated that the MHC framework is an effective and acceptable intervention among medically underserved populations during health emergencies, especially when resources are scarce. The identified factors associated with vaccination uptake demonstrated that the MHCs had the greatest impact in higher-risk communities and can be used to inform allocation of such field-level interventions in future health emergencies.

A custom tailored, evidence-based, theory-informed intervention for healthcare professionals to prevent burnout (LAGOM): study protocol for a pragmatic randomized controlled trial

BackgroundHealthcare professionals in hospitals are exposed to a high level of professional stress, time pressure, workload, and often times poor organizational support. This makes them especially susceptible to burnout. In this pragmatic randomized controlled trial, we test the hypothesis that participation in a 9-week program (LAGOM) that was designed in close collaboration with healthcare professionals, incorporating both individual and organizational aspects reduces emotional exhaustion in healthcare professionals (primary outcome).MethodsEighty four nurses and physicians working at the Charité – Universitätsmedizin Berlin and the Immanuel Hospital Berlin are automatically randomized to the LAGOM program (n = 42) or to usual care (n = 42) in a one-to-one allocation rate. The primary outcome emotional exhaustion is measured by the Maslach Burnout Inventory—Human Services Survey at baseline, post-intervention, and 1-month follow-up via an online survey. Secondary outcomes include depersonalization, personal accomplishment, subjective stress, mental well-being, self-care, self-efficacy, working conditions, mindfulness, and adverse events. Electrophysiological measures for heart rate variation analysis are captured. The PRECIS-2 tool is used to characterize the degree of pragmatism in our trial. Data analysis and primary intention-to-treat analysis using repeated measures analysis of variance are performed blind to intervention allocation. Per-protocol, subgroup, and secondary outcome analyses are conducted exploratively. An advisory board consisting of various stakeholders accompanies the study process.DiscussionIf LAGOM proves to be effective in reducing symptoms of burnout, the program could make an important contribution to tackling the problem of the very high burnout rates among healthcare professionals and become an integral part of preventive services offered by hospitals.Trial registrationGerman Clinical Trials Register, DRKS00034060. Registered 31 May 2024.

Combined strategy of device-based contrast minimization and urine flow rate-guided hydration to prevent acute kidney injury in high-risk patients undergoing coronary interventional procedures.

Contrast-associated acute kidney injury (CA-AKI) is a major complication following coronary procedures. We aimed to evaluate the effectiveness of a combination of urine flow rate-(UFR) guided hydration (RenalGuardTM) and device-based contrast media (CM) reduction (DyeVertTM) in CA-AKI prevention. Stable high-risk patients undergoing coronary procedures with the use of DyeVertTM and RenalGuardTM were prospectively included (Combined group) and matched with a similar cohort of patients treated only with RenalGuardTM in whom CM volume was controlled by operator-dependent strategies (Control group). CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL at 48 h. Overall, 55 patients were enrolled and matched with comparable controls. Patients in the Combined group were exposed to a lower CM dose (Control: 55 [30-90] mL vs. Combined: 42.1 [24.9-59.4] mL; p = 0.024). A significant interaction was found between treatment allocation and serum creatinine changes (p = 0.048). CA-AKI occurred in five (9.1%) patients in the Combined group and in 14 (25.4%) patients in the Control group (OR 0.29, 95% CI [0.09-0.88]). A combined strategy of device-based CM reduction plus UFR-guided hydration is superior to operator-dependent CM sparing strategies plus UFR-guided hydration in preventing CA-AKI in high-risk patient.

Effect of probiotics on glycemic control and lipid profiles in patients with type 2 diabetes mellitus: a randomized, double blind, controlled trial.

This double-blind, placebo-controlled, randomized (1:1) clinical trial was conducted at the West China Hospital, Sichuan University, from March to September 2017. Eligible participants included adults aged 18 years and older, living in the community, diagnosed with type 2 Diabetes Mellitus according to ADA guidelines, capable of self-managing their diabetes, and able to visit the study site for follow-up. The intervention group received 25 ml of a probiotic beverage containing with over 10^8 CFU/mL of Lactobacillus, administered four times daily. An equal volume of inactivated Lactobacillus was administered to the control group and the control group was administered the same volume of inactivated Lactobacillus. This study aimed to evaluate the effectiveness of probiotics on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes patients. The primary outcomes were changes in HbA1c and FBG levels post-intervention. Investigators, participants, and study site personnel were blinded to the treatment allocation until the conclusion of the study. This double-blind, randomized, placebo-controlled clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR-POR-17010850). Of the 490 participants screened, 213 were randomized to either the probiotics group (n = 103) or the placebo group (n = 110). After 16 weeks of follow-up, the probiotic group showed reductions in HbA1c [-0.44 (-0.66 to -0.22)] and FBG [-0.97 (-1.49 to 0.46)] post-intervention, similar to the placebo group with reductions in HbA1c [-0.33 (-0.52 to -0.15)] and FBG [-0.90 (-1.32 to -0.47)], but these changes were not statistically significant in PP and ITT analyses (P>0.05). Adverse events were similarly distributed among groups, indicating comparable safety profiles. Overall, 16-week probiotic supplementation showed no beneficial effects on glycemic control, lipid profiles, or weight. https://www.chictr.org.cn/showproj.html?proj=18421, identifier ChiCTR-POR-17010850.

Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial

Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury. In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30mL/min/1.73m2) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19). Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n=45) and 39.8% (n=35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p=0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3mL/min/1.73m2, 90% CI 0.51-8.12, p=0.06; and MAKE 6.7% (n=6) vs 15.9% (n=14); RR: 0.41, 90% CI: 0.19, 0.88, p=0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group). In this proof-of-concept study, RMC-035 did not reduce AKI 72h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes. Guard Therapeutics.