Control Arm Research Articles

Supporting GPs and people with hypertension to maximise medication use to control blood pressure: a pilot cluster RCT of the MIAMI intervention

BackgroundHypertension, or high blood pressure, is a key modifiable risk factor for heart disease and stroke. International guidelines have highlighted ‘poor adherence to treatment’ and ‘physician inertia’ as major barriers to effective blood pressure management. The Maximising Adherence, Minimising Inertia (MIAMI) intervention, a theory-based complex intervention, supports General Practitioners (GPs) and people with hypertension in maximising medication use to manage blood pressure. This pilot cluster randomised control trial (RCT) aimed to collect and analyse feasibility data to refine the MIAMI intervention and assess the feasibility of a definitive RCT.MethodA pilot cluster RCT with a MIAMI intervention arm and usual care control arm was conducted. Quantitative data collection consisting of clinical measures and a self-report questionnaire took place at baseline and twelve week follow up. Semi-structured interviews with GP and patient participants were conducted. Fidelity (as measured by a protocol checklist and through qualitative interviews) and health economics costings were assessed.ResultsSix GP practices (intervention arm n = 3, control arm n = 3) and 52 patients (intervention arm n = 25, control arm n = 27) took part. All six GP practices and 92% of patients were retained. Fidelity, as measured by a checklist and through qualitative interviews, was good but three deviations from protocol were identified. Outcomes and measures used were acceptable. The implementation cost of the MIAMI intervention was estimated at €490 per participant. The qualitative data demonstrated that the intervention was considered acceptable and feasible by both GP and patient participants, except for the urine test component, which GPs found difficult to incorporate into practice due to logistical challenges.ConclusionsThe MIAMI intervention was considered largely acceptable and feasible. Some changes to both intervention components and trial processes are required but with these in place a definitive RCT could be considered worthwhile.Trial registrationISRCTN registry, ISRCTN85009436, registered 17/1/23.

Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania

Abstract Background We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania. Methods This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18. We estimated incidence rate ratios adjusted for timing of HIV-detection (aIRR) and reported viral suppression <1000 copies/mL. Findings Among 6602 neonates enrolled October 2019-September 2021, 125 were diagnosed HIV-positive by week 12. In the intervention arm, 38/69 (55.1%) were diagnosed at birth with 35 initiating ART within two days. In the control arm, 27/56 (48.2%) were retrospectively detected HIV-positive at birth, of whom 6/56 (10.7%) died or were lost to follow-up before testing. Median age at ART initiation was 6 (intervention) versus 33 days (control). Birth test-and-treat was not associated with a significant reduction in clinical outcomes up to month-18 [53 (76.8%) versus 48 (85.7%); aIRR 0.857; 95% CI 0.505–1.492], but showed a 68% relative reduction in 6-month mortality. Viral suppression was poor overall, but improved in the intervention group at month 18 (65.7% versus 29.6%; p=0.005). Interpretation PoC test-and-treat at birth is feasible in resource-poor settings and resulted in clinically-relevant reduction of early infant mortality, though improved clinical outcomes were not sustained to month-18. Poor viral suppression may undermine early survival benefits, calling for better paediatric treatments and tailored adherence interventions.

Continuous peri-operative glucose monitoring in noncardiac surgery

BACKGROUND Glucose management is an important component of peri-operative care. The usefulness of continuous glucose monitoring (CGM) in noncardiac surgery is uncertain. OBJECTIVE To systematically assess the glycaemic profile and clinical outcome of patients equipped with a CGM device during the peri-operative period in noncardiac surgery. DESIGN Systematic review. DATA SOURCES Electronic databases were systematically searched up to July 2024. ELIGIBILITY CRITERIA Any studies performed in the peri-operative setting using a CGM device were included. Closed-loop systems also administering insulin were excluded. Analyses were stratified according to diabetes mellitus status and covered intra-operative and postoperative data. Outcomes included glycaemic profile (normal range 3.9 to 10.0 mmol l−1), complications, adverse events, and device dysfunction. RESULTS Twenty-six studies (1016 patients) were included. Twenty-four studies were not randomised, and six used a control arm for comparison. In bariatric surgery, diabetes mellitus patients had a mean ± SD glucose of 5.6 ± 0.5 mmol l−1, with 15.4 ± 8.6% time below range, 75.3 ± 5.5% in range and 9.6 ± 6.7% above range. During major surgery, diabetes mellitus patients showed a mean glucose of 9.6 ± 1.1 mmol l−1, with 9.5 ± 9.1% of time below range, 56.3 ± 13.5% in range and 30.6 ± 13.9% above range. In comparison, nondiabetes mellitus patients had a mean glucose of 6.4 ± 0.6 mmol l−1, with 6.7 ± 8.4% time below range, 84.6 ± 15.5% in range and 11.2 ± 4.9% above range. Peri-operative complications were reported in only one comparative study and were similar in CGM and control groups. Device-related adverse events were rare and underreported. In 9.21% of cases, the devices experienced dysfunctions such as accidental removal and issues with sensors or readers. CONCLUSION Due to the limited number of controlled studies, the impact of CGM on postoperative glycaemic control and complications compared with point-of-care testing remains unknown. Variability in postoperative glycaemic profiles and a device dysfunction rate of 1 in 10 suggest CGM should be investigated in a targeted surgical group.

Impact of a virtual antenatal intervention for improved diet and iron intake in Kapilvastu district, Nepal - the VALID randomized controlled trial

IntroductionCounseling, together with iron and folic acid supplements, can improve hemoglobin levels in pregnant women, but few interventions have tested a virtual method of delivering counseling. We hypothesized that a virtual counseling intervention delivered via a mobile device (mHealth) would prevent and treat anemia, compared with routine antenatal care (ANC).MethodsVirtual antenatal intervention for improved diet and iron intake (VALID) was a non-blinded parallel group two-arm, individually randomized superiority trial (1:1 allocation). Participants were pregnant women who were married, aged 13–49 years, able to answer questions, 12–28 weeks’ gestation and living in Kapilvastu district, Nepal. Women were randomized to receive routine ANC (control arm), or ANC plus a virtual antenatal intervention of two problem-solving counseling sessions via video call. The primary outcome was iron folic acid (IFA) tablet compliance (consumption on 12 or more days of the previous 14 days). Secondary outcomes were dietary diversity, promoted food consumption, iron bioavailability enhancement, and knowledge of iron-rich foods. Primary logistic regression analysis was by intention-to-treat, adjusting for baseline values.ResultsWe enrolled 319 pregnant women (161 control, 158 intervention) from 23 January 2022 to 6 May 2022 and analyzed outcomes in 144 control and 127 intervention women. Compliance with IFA increased in both arms. In the intervention arm, compliance increased by 29.7 percentage points (pp) (49.0–78.7%) and 19.8 pp. in the control arm (53.8–73.6%). Despite the more significant increase in the intervention arm, we found no intervention effect upon IFA compliance (adjusted odds ratio [aOR] 1.33; 95% confidence interval [CI]: 0.75, 2.35; p = 0.334), dietary diversity, or ANC visits. The intervention increased knowledge of iron-rich foods (coefficient 0.96; 95% CI: 0.50, 1.41; p < 0.001), consumption of promoted foods (aOR: 1.81; 95% CI: 1.08, 3.02; p = 0.023), behavior to enhance iron bioavailability (aOR: 4.41; 95% CI: 1.23, 15.83; p = 0.023), and coronavirus disease 2019 (COVID-19) knowledge (aOR: 4.06; 95% CI: 1.56, 10.54; p = 0.004). The total intervention cost was US$35,193, and the cost per pregnant woman receiving two virtual counseling sessions was US$277.ConclusionVirtual counseling can improve antenatal health behaviors, such as the consumption of promoted foods and methods to enhance bioavailability. Improved IFA consumption and ANC attendance may require additional family/community support.Clinical trial registrationhttps://www.isrctn.com/ISRCTN17842200, identifier ISRCTN17842200.

Gene expression of tight junctions in foreskin is not affected by HIV pre-exposure prophylaxis

IntroductionTight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied.MethodsWe analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman’s correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites.ResultsA high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines’ genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF.DiscussionTJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis.

A randomized trial of early cardiotoxicity in breast cancer patients receiving postoperative IMRT with or without serial cardiac dose constraints.

Optimal cardiac dose constraints in breast cancer (BC) patients undergoing postoperative intensity-modulated radiation therapy (IMRT) are unclear, although as low as possible is recommended. This trial proposes serial cardiac dose constraint to optimize cardiac safety. Postoperative BC patients eligible for anthracycline/taxanes-based chemotherapy or HER2-targeted therapy were randomized to cardiac safety arm with prespecified mean heart dose (MHD) (≤6 Gy), V30 (≤20%), and V10 (≤50%) constraints, or to a control arm with in-house protocol (mainly MHD ≤8 Gy). The primary endpoint was cumulative incidence of newly onset cardiac events within 1-year post-RT. An exploratory analysis examined the relationship between whole heart dose metrics and those of substructures. Of 199 participants, 93 were in the cardiac safety and 106 in the control arm. The cardiac safety group showed lower MHD, V10, and V30. The 1-year cardiac event incidence was slightly lower in the cardiac safety group (19.4%) compared to controls (24.9%). The LVEF and diastolic dysfunction rates were 0% and 5.4% in the study arm, and 1.9% and 8.8% in the control arm, respectively. The LAD, LV, and RV received the highest doses for left-sided patients. For right-sided patients, RA, RCA, and RV were most irradiated. The MHD, V10, and Dmax of heart significantly correlated with all substructure doses in either laterality. Our study supports the early cardiac safety profile using IMRT in BC patients receiving cardiac-toxic systemic therapy, with serial cardiac dose constraints. Combined constraints on MHD and dose-volume parameters are representative of the cardiac substructure dose.

Comparison of Letrozole Versus Combination Letrozole and Clomiphene Citrate (CC) for Ovulation Induction in Sub Fertile Women with Polycystic Ovarian Syndrome (PCOS)-An Open Label Randomized Control Trial.

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5mg letrozole and 50mg Clomiphene Citrate (CC) daily or 2.5mg letrozole alone from 2nd to 6thday of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial RegistrationThe trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020.

Intra-Articular Injection of Human Umbilical Cord-Derived Mesenchymal Stromal Cells Reduces Radiographic Osteoarthritis in an Ovine Model.

To determine if mesenchymal stromal cells (MSCs) derived from human umbilical cords (hUC) could reduce degeneration developing when injected into the knee of a large animal model of osteoarthritis (OA). Ten million culture-expanded UC-MSCs (pooled from 3 human donors) were injected in 50 μL of tissue culture medium into the left stifle joints of 7 sheep whose medial meniscus was transected 4 weeks previously. Seven other sheep had only 50 μL of medium injected as the no treatment "control" group. After 8 weeks the sheep underwent euthanasia, the joints were excised and examined macroscopically, via x-ray and magnetic resonance imaging (MRI), both via histology for degenerative and inflammatory changes and immunohistochemically to identify any human cells within the joint tissues. Activity monitoring both before meniscus transection and euthanasia was also undertaken. There was a significant reduction in the Kellgren-Lawrence x-ray score for joints injected with hUC-MSCs compared with the control joints. Likewise, macroscopic, MRI, synovitis and OARSI histology scores were all lower (better) in the joints injected with hUC-MSCs than in the control arm, but not significantly. Activity levels and synovitis scores were similar in both groups of animals. hUC-MSCs appear to modify and reduce the development of osteoarthritic changes in the ovine stifle joint after meniscal destabilization, an injury which commonly leads to OA in humans. These results are encouraging for the potential benefit of culture expanded UC-MSCs as an allogeneic cell therapy in patients who may have early OA following a meniscal injury of the knee.

Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women.

In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

A self-help mobile messaging intervention to improve subthreshold depressive symptoms among older adults in a socioeconomically deprived region of Brazil (PRODIGITAL): a pragmatic, two-arm randomised controlled trial

Subthreshold depression is a risk factor for major depression and is associated with increased morbidity and mortality, especially in older adults. There is emerging evidence that digital interventions, including self-help interventions, may reduce depressive symptoms. We aimed to evaluate the effectiveness of a mobile messaging intervention at reducing subthreshold depressive symptoms among older adults in Brazil. PRODIGITAL was a single blind, two-arm, individually randomised controlled trial conducted in 46 primary care clinics in the city of Guarulhos, Brazil. Individuals aged 60+ years were contacted by phone following a randomly ordered list for a screening assessment. Those who presented with anhedonia and/or depressed mood (Patient Health Questionnaire (PHQ)-2≥1), and who subsequently scored between 5 and 9 on the PHQ-9 were invited to participate. The intervention arm received the 'Viva Vida' digital self-help intervention consisting of automated multi-media messages sent via WhatsApp. Forty-eight audio and visual messages based on psychoeducation and behavioural activation were automatically delivered over six weeks. The control arm received a single message containing information about depression. The primary outcome was the difference in mean PHQ-9 scores between treatment arms at the three-month follow-up. All primary analyses were performed according to allocated arm with imputed data. The trial is registered with ReBEC, RBR-6c7ghfd. Participants were recruited between 8 September 2021 and 19 August 2022. Of the 454 participants enrolled, 223 were randomised to the intervention arm, 231 to the control arm. Participants' mean age was 65.3 years (SD 5.0) and 64.0% (n=292) were female. A total of 385 (84.8%) completed the three-month follow-up assessment; no difference in mean PHQ-9 scores between the treatment arms was observed (adjusted difference:-0.61; 95% CI:-1.75, 0.53; p=0.29). These results demonstrate that the Viva Vida digital self-help intervention did not help to improve subthreshold depressive symptoms amongst older adults. Further research is needed to understand why this self-help intervention was not effective in this population, and to explore how it might be adapted to achieve this goal. São Paulo Research Foundation and UK Joint Global Health Trials.

Population Health Management and Guideline-Concordant Care in CKD: A Secondary Analysis of K-CHAMP.

Gaps in guideline-concordant care for chronic kidney disease (CKD) lead to poor outcomes. The Kidney Coordinated HeAlth Management Partnership (K-CHAMP) cluster randomized trial tested the effect of a population health management intervention versus usual care on CKD progression and evidence-based care delivery in the primary care setting. K-CHAMP included adults aged 18-85 years with eGFR <60 mL/min/1.73m2 and moderate-high risk of CKD progression who were not seeing a nephrologist. The multi-faceted intervention included nephrology e-consult, pharmacist-led medication management, and patient education. In this post-hoc analysis, we evaluate the effectiveness of K-CHAMP on guideline-concordant care processes (blood pressure and glycemic control, annual albuminuria testing), and medication exposure days (ACEi/ARB, moderate-high intensity statin, SGLT-2i, GLP-1RA). Given multiplicity of outcomes, Benjamini-Hochberg method was used to control false discovery rate (FDR). All 1,596 (754 intervention, 842 usual care) enrolled patients (mean age 74±9 years, eGFR 37±8 mL/min/1.73m2, 928 (58%) female, 127 (8%) Black) were analyzed. After a median 17-month follow-up, intervention arm patients had significantly higher exposure days per year to SGLT-2i (56 vs 32 days, relative benefit 1.72, 95% CI 1.14-2.30) and GLP-1RA (78 vs 29 days, relative benefit 2.65, 95% CI 1.59-3.71) compared to usual care in adjusted analysis. At study initiation in 2019, similar proportion of patients were prescribed SGLT-2i and/or GLP-1RA in intervention and control arm (8% vs 6% respectively, rate ratio 1.23, 95% CI 0-2.99), but by 2022, prescription of these medications was significantly higher in intervention arm (44% vs 27% respectively, rate ratio 1.63, 95% CI 1.32-1.94). There was no significant difference in any process measures or exposure days to ACEi/ARB in patients with albuminuria or moderate-high intensity statin. K-CHAMP was effective in accelerating implementation of SGLT-2i and GLP-1RA but did not increase ACEi/ARB in patients with albuminuria or moderate-high intensity statin use, or improve blood pressure control, glycemic control, or albuminuria testing in individuals with CKD in the primary care setting.

Physical training augmented with whole body electronic muscle stimulation favorably impacts cardiovascular biomarkers in healthy adults – A pilot randomized controlled trial

BackgroundPhysical activity is protective against cardiovascular disease (CVD) and favorably improves CVD risk profile. However, more than 25 % of American adults report no participation in physical activity. Whole body electronic muscle stimulation (WB-EMS) training is a novel FDA-cleared technology which offers a time-efficient and adaptable method for physical training by simultaneously stimulating the main muscle groups using percutaneous electrical impulse transmission. Studies have demonstrated increased muscle mass, reduced fat mass, and improved functional capacity in sedentary individuals after training with WB-EMS, but studies evaluating the role of WB-EMS training on CVD risk profile are lacking. MethodsWe performed a pilot randomized controlled trial in healthy adults randomized to physical training with versus without WB-EMS for one session of 20 min duration per week across 16-weeks. Study participants were asked to perform their usual activities but to abstain from any strength training during the study. During each training session, all study participants wore a specifically designed vest and arm and leg straps that were connected with electrical wires to the WB-EMS device (Miha Bodytec Gersthofen, Germany). Biphasic electrical stimulation was delivered through the vest and straps (4 s on, 4 s off) at a frequency that elicited a score of 5 or 6 on the Borg rating of perceived exertion scale from study participants when each of the following muscle groups was stimulated: thighs, buttocks, lower back, upper back, latissimus dorsi, abdomen, chest and arms. These frequencies were ‘titrated’ during the first 4 weeks and were then fixed at each muscle group for each participant. Individuals randomized to no WB-EMS wore the same equipment but received no electrical stimulation. Physical training sessions were provided by personal trainers certified for WB-EMS training and consisted of a fixed number of exercises and repetitions. We measured and compared several clinically important cardiovascular parameters at baseline and post-intervention. ResultsSeventy-eight participants were recruited between January 2021 and March 2022 with a mean age of 35.9 ± 11.2, 61.3 % females, median BMI 24.3 (21.8, 28.1); N = 46 were randomized to intervention group and N = 32 were randomized to the control group. Eighteen (23 %) participants dropped out of the trial, including 9 participants from the EMS arm (19.6 %), and 9 participants in control arm (28.1 %). There was no significant differences in the rate of dropping out of the WB-EMS and control groups (p = 0.27). Those in the intervention group compared to controls exhibited the following changes after 16-weeks of training: waist:hip ratio (∆ -0.03 ± 0.05, p = 0.01 vs. -0.01 ± 0.0, p = 0.1), peripheral endothelial function, measured using reactive hyperemia peripheral arterial tonometry (∆: 0.02 ± 0.1, p = 0.5 vs. -0.20 ± 0.3 p = 0.05), high-sensitivity C-reactive protein (∆: 0.06 ± 0.7, p = 0.3 vs. 0.20 ± 2.3 p = 0.02), total cholesterol (∆: −1.7 ± 25.1, p = 0.3 vs. 19.2 ± 26.5, p < 0.001), high density lipoprotein (∆: 2.02 ± 6.6, p = 0.2 vs. 3.6 ± 7.5 p = 0.01) and low density lipoprotein cholesterol (∆: 0.5 ± 26.7, p = 0.4 vs. 17.1 ± 23.2, p < 0.001). ConclusionOnce weekly physical training with WB-EMS in healthy adults resulted in either improved or stable biomarkers of cardiovascular risk, which either remained stable or worsened in those undergoing conventional training alone. Thus WB-EMS may provide an effective and time-efficient form of physical training that may be considered in those unable or unwilling to perform exercise conventionally.

Motion Controller for Multi-Joint Robotic Arm with Deep Cascade Gated Bayesian Broad Learning System

Intelligent controllers based on the broad learning system can simplify the process of model parameter adjustment, finding wide applications in the motion control of multi-joint robotic arms. However, motion controllers for multi-joint robotic arms based on broad learning system exhibit insufficient precision and overlook the impact of joint motion commonalities on controller design. Therefore, this paper proposes a novel motion control strategy for a multi-joint robotic arm based on a deep cascade feature-enhancement gated Bayesian broad learning system. Firstly, the motion controller of the deep cascade feature-enhancement Bayesian broad learning system is constructed to enhance the robotic arm motion control precision. Secondly, an incremental node generation module with an attention-gated mechanism is constructed to capture the unique motion characteristics of the target joints, which is further combined with model generalization to simplify the motion control process of the multi-joint robotic arm. Finally, controller convergence is enhanced by combining it with the Lyapunov theory to constrain the learning parameters. Simulations and physical experiments are designed to verify the feasibility and superiority of the proposed motion control strategy. The results demonstrated that the strategy improved the accuracy of robotic arm motion control, with the root mean square error in position tracking reduced to 0.0019 rad. This represents a 93.39% reduction in error compared to existing techniques.

Design and Control Co-Optimization for Dynamic Loco-Manipulation With a Robotic Arm on a Quadruped Robot

Abstract Research in quadrupedal robotics is transitioning to studies into loco-manipulation, featuring fully articulated robotic arms mounted atop these robots. Integrating such arms enhances the practical utility of legged robots, paving the way for expanded applications like industrial inspection and search and rescue. Existing literature commonly employs a six-degree-of-freedom (six-DoF) arm directly mounted to the robot, which inherently adds significant weight and reduces the available payload for manipulation tasks. Our study explores an optimized combination of arm configuration and control framework by strategically reducing the DoFs and leveraging the quadruped robot’s inherent agile mobility. We demonstrate that by minimizing the DoFs to just one, a range of canonical loco-manipulation tasks can still be accomplished. Some tasks even show improved performance with fewer robotic arm DoFs due to the higher torque motor used in the design, allowing more of the robot’s payload to be used for manipulation. We designed our optimized one-DoF robotic arm and the control framework and tested it on top of a Unitree Aliengo. Our design outperforms conventional six-DoF counterparts in lifting capacity, achieving an impressive 8 kg payload compared to the 2 kg maximum payload of industry-standard six-DoF robotic arms on the same quadruped platform.

STOPTHEBURN: A Randomized Controlled Trial of Death Cafés for Burnout Prevention in Intensive Care Unit Employees.

Rationale: Effective interventions to prevent burnout among intensive care unit (ICU) clinicians are urgently needed. Death cafés, group discussions about death, build a sense of community and create a space for reflection on distressing events. Objective: To assess whether participation in regular death cafés can prevent burnout in ICU clinicians (physicians, nurses, pharmacists, therapists). Methods: A randomized clinical trial was conducted from July 2020 to December 2022 in 10 ICUs in Louisiana. Subjects were randomized to attend four psychotherapist-facilitated virtual death cafés or to a control arm. The primary outcome was burnout defined by the Maslach Burnout Inventory-Human Services Survey at 6 months. Depression and anxiety scores were measured, as were qualitative data on stressors, coping, and death café experience. Results: Among 340 clinicians who were screened and gave consent (171 physicians, 169 nonphysicians), 251 participated (mean age, 31.0 ± 6.8 years; 63% female; 72% White; 37% nurses, 27% residents, 25% interns, 11% other). Burnout prevalence was 19% at baseline. Of 136 participants who completed the 6-month follow-up, no significant differences were found between intervention and control for the primary outcome (18% vs. 25%; unadjusted odds ratio, 0.64; 95% confidence interval, 0.26-1.57; P = 0.33). There were no differences in anxiety or depression. Notably, the study was limited by an inability to achieve target enrollment and a high attrition rate (46%). Conclusions: Virtual death cafés were unable to reduce burnout, although the study was underpowered to detect differences between groups. Clinical trial registered with clinicaltrials.gov (NCT04347811).

Short-term outcomes of oropharyngeal administration of colostrum in preterm neonates: a double-blind placebo-controlled randomized trial.

The oropharyngeal administration of colostrum (OAC) in neonates has several benefits. To investigate the short-term outcomes of OAC in preterm neonates. We performed this two-arm, double-blind, placebo-controlled randomized trial at a tertiary neonatal center in Iran in 2021-2023. The intervention and control arms received 0.2 mL of their mother's colostrum or distilled water via oropharyngeal administration every 6 h for 3 days starting from birth until 72 h of age. The main study outcomes were neonatal death, the incidence of necrotizing enterocolitis (NEC), sepsis, retinopathy of prematurity (ROP), length of hospital stay, and period to full enteral feeding. A regression analysis was used to adjust for possible confounders. A total of 126 neonates (mean gestational age, 30.05 weeks) were randomized to the intervention and placebo groups (n=63 each) and had a mean ± SD weight of 1247 ± 193 vs 1156 ± 215 g (P=0.013) and 1- and 5-min Apgar scores of 6.35 vs 5.38 (P=0.003) and 7.84 vs 7.13 (P=0.001), respectively. The mortality rate was 12.7% in the intervention group versus 14.3% in the placebo group (P=0.794). The NEC rate was significantly lower in the intervention versus placebo arm (11.1% vs. 28.6%, respectively; P=0.010), as was the clinically suspected sepsis rate (15.9% vs. 39.7%, respectively; P=0.004). The ROP and bronchopulmonary dysplasia rates did not differ significantly between groups after the adjustment for confounders. The mean length of hospital stay was shorter in the intervention group (26.1 vs. 37.32; P=0.023). Moreover, the mean duration of antibiotic therapy and period to full feeding were significantly shorter in the intervention group. OAC could effectively decrease the incidence of complications in preterm infants and facilitate earlier patient discharge.

Efficacy of a Multimodal Digital Behavior Change Intervention on Lifestyle Behavior, Cardiometabolic Biomarkers, and Medical Expenditure: Protocol for a Randomized Controlled Trial.

The US Preventive Services Task Force recommends providers offer individualized healthy behavior interventions for all adults, independent of their risk of cardiovascular disease. While strong evidence exists to support disease-specific programs designed to improve multiple lifestyle behaviors, approaches to adapting these interventions for a broader population are not well established. Digital behavior change interventions (DBCIs) hold promise as a more generalizable and scalable approach to overcome the resource and time limitations that traditional behavioral intervention programs face, especially within an occupational setting. We aimed to evaluate the efficacy of a multimodal DBCI on (1) self-reported behaviors of physical activity, nutrition, sleep, and mindfulness; (2) cardiometabolic biomarkers; and (3) chronic disease-related medical expenditure. We conducted a 2-arm randomized controlled trial for 12 months among employees of an academic health care facility in the United States. The intervention arm received a scale, a smartphone app, an activity tracker, a video library for healthy behavior recommendations, and an on-demand health coach. The control arm received standard employer-provided health and wellness benefits. The primary outcomes of the study included changes in self-reported lifestyle behaviors, cardiometabolic biomarkers, and chronic disease-related medical expenditure. We collected health behavior data via baseline and quarterly web-based surveys, biometric measures via clinic visits at baseline and 12 months, and identified relevant costs through claims datasets. A total of 603 participants were enrolled and randomized to the intervention (n=300, 49.8%) and control arms (n=303, 50.2%). The average age was 46.7 (SD 11.2) years, and the majority of participants were female (80.3%, n=484), White (85.4%, n=504), and non-Hispanic (90.7%, n=547), with no systematic differences in baseline characteristics observed between the study arms. We observed retention rates of 86.1% (n=519) for completing the final survey and 77.9% (n=490) for attending the exit visit. This study represents the largest and most comprehensive evaluation of DBCIs among participants who were not selected based on their underlying condition to assess its impact on behavior, cardiometabolic biomarkers, and medical expenditure. ClinicalTrials.gov NCT04712383; https://clinicaltrials.gov/study/NCT04712383. RR1-10.2196/50378.

Control of Multi-Robot Arms in Object Retrieval Based on Human-Machine Interface

Multi-robot arm control is the result of the development of advanced robotics technology. With the advancement in the field of human-machine interface, controlling robot arms has become more efficient and can be done intuitively by humans. In this study, we designed three robot arms of 4-DoF, each of which is controlled by a computer in a visual program interface. This research aims to develop a human-machine interface-based multi-robot arm control system that allows humans to interact with the robots directly. The movement method of each robot uses Trajectory Planning, which works when the operator gives motion commands through the interface display. Multi-robot communication with a computer using USB hub serial format. The computer is the master, and each Arduino on the robot is the enslaved. Three robot arms have been tested and controlled by the HMI computer, and all of them move according to the commands of the operator. The time required by each robot to complete its mission is ± 10 seconds. The results of this study are expected to open new opportunities in the application of robotics in various fields, such as the manufacturing industry, health services, and transportation.

Safer and targeted use of antipsychotics in youth: an embedded, pragmatic randomized trial

BackgroundAntipsychotic medications (AP) are inappropriately prescribed to young people. The goal of this pragmatic trial was to test a four‐component approach to improved targeting of antipsychotic prescribing to people aged ≥3 and &lt;18 years.MethodsClinicians in four health systems were cluster randomized by the number of previous AP orders and service line – specialty mental health and all others. Intervention arm clinicians received a best practice alert and child psychiatrist consultation and feedback. Families received system navigation and expedited access to psychotherapy. Primary outcomes were total days' supply of AP medication and proportion of youth with any AP supply at 6 months. We estimated the log‐odds of AP use at 6 months and the relative rate of AP over 6 months. The Safer and Targeted Use of Antipsychotics in Youth (SUAY) trial took place between 3/2018 and 12/2020.ResultsThe trial enrolled 733 patients. The odds ratio (OR) comparing use at 6 months was 0.75 (95% CI: 0.52, 1.09). The mean number of days using AP was 118.5 for intervention patients and 128.2 for control patients (relative risk [RR] = 0.92; 95% CI: 0.81–1.04). Exploratory heterogeneity of treatment effects (HTE) was not detected in groups defined by age, gender, provider specialty, and insurance type. HTE by race/ethnicity was present: among youth of color, mean days' supply was 103.2 for intervention arm and 131.2 for the control arm (RR 0.79, 95% CI: 0.67–0.93). Among secondary outcomes, only new psychotherapy referrals differed with 44.3% (n = 154) of intervention participants having a new order for psychotherapy compared to 33.5% (n = 129) in the control arm (OR 1.47: 95% CI: 1.01–2.14).ConclusionsThis intervention did not result in less AP use at 6 months or a reduction in the days' supply of AP medication, although psychotherapy orders increased. The intervention may be effective for some subgroups.

Fastidious adherence to 0/1-hour high-sensitivity troponin T testing reduces emergency department length of stay in patients presenting with suspected acute coronary syndromes

Abstract Background High-sensitivity cardiac troponins (hs-cTn) are key clinical biomarkers in patients presenting with suspected acute coronary syndromes (ACS) to Emergency Departments (EDs). They have facilitated rapid 0h/1h troponin testing protocols, leading to safe, effective, and efficient triage of patients. However, early distinction of myocardial infarction (MI), which has a reported frequency of less than 10% in most cohorts, from the apparently stable hs-cTn elevations of chronic myocardial injury (CMI) remains a challenge. Often CMI patients require confirmation by further testing and observation, prolonging patient length of stay. Further, reliably obtaining serial hs-cTn samples at 60-minutes in a busy ED setting may be difficult. A potential explanation for only 5-6% of Australian sites adopting 0h/1h hs-cTn testing. Methods and Results We undertook a case-control study between March and August 2023 among patients with suspected ACS presenting to Liverpool Hospital ED (Sydney, Australia). 185 patients (cases) underwent hs-cTnT sampling at 30- and 60-minutes (± 5 minutes) after baseline. Diagnosis of MI was made in 8.6%, 35.7% were placed into a further observation group and MI ruled-out in 55.7%. The latter two groups were matched to 169 patients (controls) who received ‘usual’ care, which was a 0h/1h hs-cTnT testing protocol. The case and control arms were matched by age, gender, time from symptom onset and main presenting symptom. Control patients had a median sampling interval of 118 [85 to 174] minutes, rather 60 minutes as the protocol directs. When comparing the paired differences between the case and control arms, there was a mean reduction in length of stay of 104 (95% CI: 41 to 186, P = 0.01) and 47 (95% CI: 11 to 84, P = 0.01) minutes, for the observation and rule-out MI groups respectively. The figure shows the distribution of lengths of stay by group. Among the rule-out group, Wilcoxon signed rank test indicated the control arm had a longer median length of stay of 6.3 [5.1 to 8.4] hours, compared to 5.0 [4.5 to 7.1] hours in the case arm (P=0.005). Similarly, in the further observation group, control patients also had a longer median length of stay of 9.2 [6.9 to 10.4] hours compared to case patients of 8.1 [5.1 to 10.3] hours (P = 0.009). At 30-days, ED representation rates were 10.7% in controls and 8.3% in cases, rehospitalisation 3.6% in controls and 5.3% in cases, cardiac death 0% in both arms and non-cardiac death 1% in both arms. There were no differences in event rates between each arm (P &amp;gt; 0.05). Conclusion Accurate 0h/1h hs-cTnT testing reduces patient length of stay in ED and offers more personalised prediction of MI risk. The importance of adherence to protocol-directed sampling times is clear, where further studies are required regarding routine implementation in a busy ED setting.Exact 60 min TnT and LOSOutcomes at 30 days