Intervention Dose Research Articles

Effect of Nuts on Markers of Inflammation and Oxidative Stress: A Narrative Review.

Oxidative stress and inflammation are mediators in the pathophysiology of several non-communicable diseases (NCDs). Tree nuts and peanuts lower risk factors of cardiometabolic disease, including blood lipids, blood pressure and insulin resistance, among others. Given their strong antioxidant/anti-inflammatory potential, it is plausible that nuts may also exert a favorable effect on inflammation and oxidative stress. Evidence from systematic reviews and meta-analyses of cohort studies and randomized controlled trials (RCTs) suggest a modest protective effect of total nuts; however, the evidence is inconsistent for specific nut types. In this narrative review, the state of evidence to date is summarized for the effect of nut intake on biomarkers of inflammation and oxidative stress, and an attempt is made to define the gaps in research while providing a framework for future research. Overall, it appears that some nuts, such as almonds and walnuts, may favorably modify inflammation, and others, such as Brazil nuts, may favorably influence oxidative stress. There is a pressing need for large RCTs with an adequate sample size that consider different nut types, and the dose and duration of nut intervention, while evaluating a robust set of biomarkers for inflammation and oxidative stress. Building a stronger evidence base is important, especially since oxidative stress and inflammation are mediators of many NCDs and can benefit both personalized and public health nutrition.

Water Extract of Chrysanthemum indicum L. Flower Inhibits Capsaicin-Induced Systemic Low-Grade Inflammation by Modulating Gut Microbiota and Short-Chain Fatty Acids.

Systemic low-grade inflammation induced by unhealthy diet has become a common health concern as it contributes to immune imbalance and induces chronic diseases, yet effective preventions and interventions are currently unavailable. The Chrysanthemum indicum L. flower (CIF) is a common herb with a strong anti-inflammatory effect in drug-induced models, based on the theory of "medicine and food homology". However, its effects and mechanisms in reducing food-induced systemic low-grade inflammation (FSLI) remain unclear. This study showed that CIF can reduce FSLI and represents a new strategy to intervene in chronic inflammatory diseases. In this study, we administered capsaicin to mice by gavage to establish a FSLI model. Then, three doses of CIF (7, 14, 28 g·kg-1·day-1) were tested as the intervention. Capsaicin was found to increase serum TNF-α levels, demonstrating a successful model induction. After a high dose of CIF intervention, serum levels of TNF-α and LPS were reduced by 62.8% and 77.44%. In addition, CIF increased the α diversity and number of OTUs in the gut microbiota, restored the abundance of Lactobacillus and increased the total content of SCFAs in the feces. In summary, CIF inhibits FSLI by modulating the gut microbiota, increasing SCFAs levels and inhibiting excessive LPS translocation into the blood. Our findings provided a theoretical support for using CIF in FSLI intervention.

Adaptation of a Behavioural Activation Intervention for Depression in People with Diabetes in Bangladesh and Pakistan: DiaDeM Intervention

The cultural tailoring of interventions is a cost-effective approach to reach underserved populations. There are multiple frameworks for intervention adaptation, however, information on their use in practice, and sources to guide the adaptations is limited. The aim of this paper is to describe our experience using intervention adaptation frameworks and illustrate the adaptation process of a behavioural activation intervention for depression in people with type 2 diabetes in Bangladesh and Pakistan. We were guided by the intervention mapping adaptation framework for development and evaluation of health interventions and the Bernal and the Escoffery frameworks to address the cultural components of the adaptation. We performed a needs assessment, developed a logic model and systematically searched for available evidence-based interventions. To obtain evidence to guide the adaptations, we conducted a literature review, a qualitative study and workshops with community, expert advisory panels and a co-design group which systematically fed into the adaptation process. We co-produced the materials (training manual and booklet) with stakeholders. Finally, an implementation and evaluation plan was produced to test the feasibility and effectiveness of the intervention. We selected 3 interventions that had a good fit for our target population. Guided by the logic model, we identified core components of these interventions that could not be changed. We made changes in the language, pictures, illustrations, intervention dose and delivery (self-guided versus facilitator), inclusion of carers and/or family members, and training intensity. We developed a protocol to test the feasibility and effectiveness of the intervention considering key changes from the original intervention and the characteristics of the new setting and target population. Intervention adaptation frameworks proved to be valuable tools to guide the intervention process, and ensure the inclusion of multiple sources of evidence and key stakeholders.

Cognitive Behavioral Sleep Self-Management Intervention for Young Adults With Type 1 Diabetes (NCT04975230).

The purpose of this study was to explore perceptions of the first dose of a cognitive behavioral sleep self-management intervention (CB-sleep) among young adults aged 18 to 25 years with type 1 diabetes (T1D). We used a qualitative descriptive approach to conduct in-depth semi-structured focused interviews with a purposive sample of 16 young adults with T1D, transitioning from adolescence to early adulthood. Interviews were audio-recorded, transcribed verbatim, and analyzed using qualitative content analysis. Participants described their sleep knowledge (previous, new, and additional), sleep health goals, along with barriers and facilitators of the CB-sleep intervention. Based on these results, we suggest CB-sleep is a useful modality with the potential to support sleep self-management in young adults with T1D during this complex life transition. Furthermore, CB-sleep could be incorporated into an existing diabetes self-management education and support program after pilot testing and determining efficacy to improve sleep and glycemic health.

Exercise dosage to facilitate the recovery of balance, walking, and quality of life after stroke.

Although aerobic training (AT) and resistance training (RT) are recommended after stroke, the optimal dosage of these interventions and their effectiveness on balance, walking capacity, and quality of life (QoL) remain conflicting. Our study aimed to quantify the effects of different modes, dosages and settings of exercise therapy on balance, walking capacity, and QoL in stroke survivors. PubMed, CINHAL, and Hinari databases were searched for randomised controlled trials (RCTs) evaluating the effects of AT and RT on balance, walking, and QoL in stroke survivors. The treatment effect was computed by the standard mean differences (SMDs). Twenty-eight trials (n = 1571 participants) were included. Aerobic training and RT interventions were ineffective on balance. Aerobic training interventions were the most effective in improving walking capacity (SMD = 0.37 [0.02, 0.71], p = 0.04). For walking, capacity, a higher dosage (duration ≥ 120 min/week; intensity ≥ 60% heart rate reserve) of AT interventions demonstrated a significantly greater effect (SMD = 0.58 [0.12, 1.04], p = 0.01). Combined AT and RT improved QoL (SMD = 0.56 [0.12, 0.98], p = 0.01). Hospital located rehabilitation setting was effective for improving walking capacity (SMD = 0.57 [0.06, 1.09], p = 0.03) compared with home and/or community and laboratory settings. Our findings showed that neither AT nor RT have a significant effect on balance. However, AT executed in hospital-located settings with a higher dose is a more effective strategy to facilitate walking capacity in chronic stroke. In contrast, combined AT and RT is beneficial for improving QoL. A high dosage of aerobic exercise, duration ≥ 120 min/week; intensity ≥ 60% heart rate reserve is beneficial for improving walking capacity.

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial

Despite the introduction of new monoclonal antibodies and oral therapies for the treatment of ulcerative colitis, clinical remission rates remain low, underscoring the need for innovative treatment approaches. We assessed whether guselkumab plus golimumab combination therapy was more effective for ulcerative colitis than either monotherapy. We did a randomised, double-blind, controlled, proof-of-concept trial at 54 hospitals, academic medical centres, or private practices in nine countries. Eligible adults (aged ≥18 to 65 years) had a confirmed diagnosis of ulcerative colitis at least 3 months before screening and moderately-to-severely active ulcerative colitis (Mayo score 6-12) with a centrally-read baseline endoscopy subscore of 2 or higher. Patients were randomly assigned (1:1:1) using a computer-generated randomisation schedule to combination therapy (subcutaneous golimumab 200 mg at week 0, subcutaneous golimumab 100 mg at weeks 2, 6, and 10, and intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab monotherapy 100 mg every 8 weeks for 32 weeks), golimumab monotherapy (subcutaneous golimumab 200 mg at week 0 followed by subcutaneous golimumab 100 mg at week 2 and every 4 weeks thereafter for 34 weeks), or guselkumab monotherapy (intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab 100 mg every 8 weeks thereafter for 32 weeks). The primary endpoint was clinical response at week 12 (defined as a ≥30% decrease from baseline in the full Mayo score and a ≥3 points absolute reduction with either a decrease in rectal bleeding score of ≥1 point or a rectal bleeding score of 0 or 1). Efficacy was analysed in the modified intention-to-treat population up to week 38, which included all randomly assigned patients who received at least one (partial or complete) study intervention dose. Safety was analysed up to week 50, according to study intervention received among all patients who received at least one (partial or complete) dose of study intervention. This trial is complete and is registered with ClinicalTrials.gov, NCT03662542. Between Nov 20, 2018, and Nov 15, 2021, 358 patients were screened for eligibility, of whom 214 patients were randomly assigned to combination therapy (n=71), golimumab monotherapy (n=72), or guselkumab monotherapy (n=71). Of the 214 patients included, 98 (46%) were women and 116 (54%) were men and the mean age was 38·4 years (SD 12·0). At week 12, 59 (83%) of 71 patients in the combination therapy group had achieved clinical response compared with 44 (61%) of 72 patients in the golimumab monotherapy group (adjusted treatment difference 22·1% [80% CI 12·9 to 31·3]; nominal p=0·0032) and 53 (75%) of 71 patients in the guselkumab monotherapy group (adjusted treatment difference 8·5% [-0·2 to 17·1; nominal p=0·2155). At week 50, 45 (63%) of 71 patients in the combination therapy group, 55 (76%) of 72 patients in the golimumab monotherapy group, and 46 (65%) of 71 patients in the guselkumab monotherapy group had reported at least one adverse event. The most common adverse events were ulcerative colitis, upper respiratory tract infection, headache, anaemia, nasopharyngitis, neutropenia, and pyrexia. No deaths, malignancies, or cases of tuberculosis were reported during the combination induction period. One case of tuberculosis was reported in the combination therapy group and one case of colon adenocarcinoma was reported in the guselkumab monotherapy group; both occurred after week 12. Two deaths were reported after the final dose of study intervention (poisoning in the combination therapy group and COVID-19 in the guselkumab monotherapy group). Data from this proof-of-concept study suggest that combination therapy with guselkumab and golimumab might be more effective for ulcerative colitis than therapy with either drug alone. These findings require confirmation in larger trials. Janssen Research and Development.

Abstract WP67: Determining The Dosage Of BCI-FES Intervention For Optimal Motor Recovery Of Stroke Survivors

Brain-computer interface (BCI)-mediated functional electrical stimulation (FES) of stroke impaired upper extremity motor function has been shown to improve motor capacity but accurate dosing of BCI-FES has not been determined. This analysis seeks to determine whether participants with a greater number of FES runs realized greater change in the Stroke Impact Scale-Hand Function subdomain (SIS-hf) as a result of intervention. Participants (n = 14, 8 females, mean age = 61.3 ± 11.5 yr) in an ongoing study completed up to 30 hours of BCI-FES intervention. These participants were grouped post hoc into two groups, high (greater than 184 runs) and low (less than 184 runs) dosages of BCI-FES intervention. All participants underwent a series of behavioral tests at baseline and completion which included the Stroke Impact Scale-hand function (SIS-hf) domain. Group mean change in SIS-hf scores were compared using an independent samples t-test. Participants who completed 15 intervention sessions with fewer than 184 BCI-FES runs (n = 7) had a greater mean increase in SIS-hf scores (group mean difference = 2.29 ± 4.65) compared to those who completed more than 184 runs with paired FES (n = 7, group mean difference = 0.86 ± 1.68). These group mean differences as a result of intervention were not statistically significant t (7.54) = 0.77, p = 0.47. As expected, SIShf scores increased in both low-dose and high-dose groups of participants; however, the present results suggest that increasing the dose (i.e., number of runs) of BCI-FES intervention may not necessarily result in greater motor recovery in stroke participants.

First-line lenvatinib plus pembrolizumab plus chemotherapy versus chemotherapy in advanced/metastatic gastroesophageal adenocarcinoma (LEAP-015): Safety run-in results.

411 Background: LEAP-015 (NCT04662710) is a randomized, open-label, 2-part, phase 3 study of the safety and efficacy of lenvatinib + pembrolizumab + chemotherapy as a first-line treatment for advanced/metastatic gastroesophageal adenocarcinoma. We report findings from part 1, the safety run-in, of LEAP-015. Methods: Eligible patients had untreated, HER2-negative, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma, measurable disease per RECIST v1.1, and ECOG performance status 0 or 1. In part 1, patients received induction with IV pembrolizumab 400 mg Q6W (×2) + oral lenvatinib 8 mg QD + investigator choice of chemotherapy (capecitabine + oxaliplatin [CAPOX] Q3W ×4 or 5-fluorouracil + leucovorin + oxaliplatin [mFOLFOX6] Q2W ×6) and consolidation with pembrolizumab 400 mg Q6W for ≤16 doses + lenvatinib 20 mg QD; dose-limiting toxicities (DLTs), defined as selected prespecified grade ≥3 adverse events (AEs) or any-grade thromboembolic events, were evaluated for 21 days after the first dose of study intervention. If ≥3 DLTs occurred in either oxaliplatin-containing regimen, then enrollment in part 2 may be delayed to allow for the examination of safety data and to consider design changes. In part 1, the primary end point was safety and tolerability in all patients. Preliminary efficacy was also assessed in part 1. Objective response and disease control rate were assessed per RECIST version 1.1 by blinded independent central review. Results: In part 1, 15 pts received ≥1 dose of lenvatinib + pembrolizumab + chemotherapy. 1 DLT of grade 3 asthenia occurred in the CAPOX cohort and 1 DLT of grade 4 neutropenia occurred in the FOLFOX cohort. Median time from first dose to data cutoff (Oct 13, 2021) was 7 mo (range, 7-9). Treatment-related AEs occurred in 14 patients (93%), with grade 3/4 events in 8 patients (53%). 4 patients (27%) discontinued any drug because of a treatment-related AE, and no patient discontinued all drugs because of a treatment-related AE. No patients died because of a treatment-related AE. No grade ≥3 immune-mediated AEs or infusion reactions occurred. Objective response was reported in 11 of 15 patients (73%; 95% CI, 45-92) who received ≥1 dose of treatment. Disease control rate was reported in 14 of 15 patients (93%; 95% CI, 68-100) who received ≥1 dose of treatment. Conclusions: In the safety run-in of LEAP-015, lenvatinib + pembrolizumab + chemotherapy was associated with a manageable safety profile in the first-line treatment of advanced/metastatic gastroesophageal adenocarcinoma. Preliminary antitumor activity was observed for lenvatinib + pembrolizumab + chemotherapy. Part 2 will evaluate the efficacy and safety of lenvatinib + pembrolizumab + chemotherapy versus chemotherapy in this same patient population and patient accrual is ongoing. Clinical trial information: NCT04662710 .

KEYMAKER-U06 substudy 06A trial in progress: A phase 1/2 study of investigational agents with pembrolizumab (pembro) plus chemotherapy (chemo) or lenvatinib in PD-1/L1 treatment-naïve advanced esophageal cancer.

TPS487 Background: Immunotherapy has improved clinical outcomes in esophageal carcinoma; however, patients with advanced esophageal cancer that progresses after first-line chemo continue to have limited treatment options and poor prognosis. KEYMAKER-U06 substudy 06A (NCT05342636) is evaluating pembro (anti–PD-1) + investigator choice of chemo (irinotecan or paclitaxel), MK-4280A, a coformulation of pembro and favezelimab (anti-LAG3) + chemo, pembro + MK-4830 (anti-ILT4) + chemo, and pembro + MK-4830 + lenvatinib (multitargeted RTK inhibitor) for the second-line treatment of patients with PD-1/L1 treatment-naive advanced esophageal squamous cell carcinoma (ESCC). Methods: KEYMAKER-U06 substudy 06A is a phase 1/2, multicenter, open-label study comprising a safety lead-in phase and an efficacy phase. Adults with histologically or cytologically confirmed metastatic or locally advanced ESCC, who experienced disease progression on 1 prior line of therapy, have not received anti-PD-1/L1 therapy, any immune-modulating therapy, and/or VEGF targeted therapy, have measurable disease per RECIST v1.1 confirmed by blinded independent central review (BICR), and have an Eastern Cooperative Oncology Group performance status of 0 or 1 are eligible. Patients are being allocated to 1 of 4 treatment arms: pembro 200 mg IV Q3W + investigator choice of chemo (paclitaxel 80-100 mg/m2 IV days 1, 8, and 15 of every 28-day cycle or irinotecan 180 mg/m2 day 1 of every 14-day cycle) (arm 1), MK-4280A (pembro 200 mg/favezelimab 800 mg IV day 1 then Q3W) + investigator choice of chemo (arm 2), pembro 200 mg IV Q3W + MK-4830 800 mg IV Q3W + investigator choice of chemo (arm 3), or pembro 200 mg IV Q3W + MK-4830 800 mg IV Q3W + lenvatinib 20 mg orally once daily (arm 4). Arms 2-4 will have a safety lead-in phase; arm 1 will not have a safety lead-in phase because the safety and tolerability of pembro + chemo has been established in multiple phase 3 studies in the first-line treatment setting. The safety lead-in phase includes 10 patients who will be closely monitored for dose-limiting toxicities (DLTs) for 21 days after the first dose of study intervention. If ≥4 patients experience DLTs in any treatment arm, then enrollment in the efficacy phase may be delayed to allow for examination of safety data and to consider design changes. If ≤3 patients experience DLTs, up to 30 patients per arm will be enrolled (inclusive of the 10 patients from the safety lead-in) for efficacy assessment. In the safety lead-in phase, the primary end point is safety/tolerability assessed by DLTs, adverse events (AEs), and discontinuation of treatment due to AEs. In the efficacy phase, the primary end point is ORR per RECIST v1.1 by BICR, and secondary end points are PFS and DOR, per RECIST v1.1 by BICR, and OS and safety/tolerability. Enrollment in this study is ongoing. Clinical trial information: NCT05342636 .

Effect of anthocyanins on gut health markers, Firmicutes-Bacteroidetes ratio and short-chain fatty acids: a systematic review via meta-analysis

Researchers discovered that diets rich in anthocyanin-rich fruits and vegetables significantly impacted gut flora. To conclude, large-scale randomized controlled clinical trials are challenging to conduct; therefore, merging data from multiple small studies may aid. A systematic review collects and analyses all research on a particular subject and design. This comprehensive review and meta-analysis examined the influence of dietary anthocyanins on Firmicutes/Bacteroide (Fir/Bac) and short-chain fatty acids (SCFAs) content. The current meta-analysis followed the guidelines of PRISMA—the preferred reporting items for systematic reviews and meta-analyses. Diets high in anthocyanins substantially reduced the Fir/Bac ratio in the assessed trials. Among three SCFAs, the highest impact was observed on acetic acid, followed by propionic acid, and then butanoic acid. The meta-analysis results also obtained sufficient heterogeneity, as indicated by I2 values. There is strong evidence that anthocyanin supplementation improves rodent gut health biomarkers (Fir/Bac and SCFAs), reducing obesity-induced gut dysbiosis, as revealed in this systematic review/meta-analysis. Anthocyanin intervention duration and dosage significantly influenced the Fir/Bac ratio and SCFA. Anthocyanin-rich diets were more effective when consumed over an extended period and at a high dosage.

Comparative effects of kinect-based versus therapist-based constraint-induced movement therapy on motor control and daily motor function in children with unilateral cerebral palsy: a randomized control trial

BackgroundConstraint-induced movement therapy (CIMT) is a prominent neurorehabilitation approach for improving affected upper extremity motor function in children with unilateral cerebral palsy (UCP). However, the restraint of the less-affected upper extremity and intensive training protocol during CIMT may decrease children’s motivation and increase the therapist’s workload and family’s burden. A kinect-based CIMT program, aiming to mitigate the concerns of CIMT, has been developed. The preliminary results demonstrated that this program was child-friendly and feasible for improving upper extremity motor function. However, whether the kinect-based CIMT can achieve better or at least comparable effects to that of traditional CIMT (i.e., therapist-based CIMT) should be further investigated. Therefore, this study aimed to compare the effects of kinect-based CIMT with that of therapist-based CIMT on upper extremity and trunk motor control and on daily motor function in children with UCP.MethodsTwenty-nine children with UCP were recruited and randomly allocated to kinect-based CIMT (n = 14) or therapist-based CIMT (n = 15). The intervention dosage was 2.25 h a day, 2 days a week for 8 weeks. Outcome measures, namely upper extremity and trunk motor control and daily motor function, were evaluated before and after 36-h interventions. Upper extremity and trunk motor control were assessed with unimanual reach-to-grasp kinematics, and daily motor function was evaluated with the Revised Pediatric Motor Activity Log. Between-group comparisons of effectiveness on all outcome measures were analyzed by analysis of covariance (α = 0.05).ResultsThe two groups demonstrated similar improvements in upper extremity motor control and daily motor function. In addition, the kinect-based CIMT group demonstrated greater improvements in trunk motor control than the therapist-based CIMT group did (F(1,28) > 4.862, p < 0.036).ConclusionKinect-based CIMT has effects comparable to that of therapist-based CIMT on UE motor control and daily motor function. Moreover, kinect-based CIMT helps decrease trunk compensation during reaching in children with UCP. Therefore, kinect-based CIMT can be used as an alternative approach to therapist-based CIMT.Trial registration: ClinicalTrials.gov Identifier: NCT02808195. Registered on 2016/06/21, https://clinicaltrials.gov/ct2/show/NCT02808195.

A multi-center, randomized, 12-month, parallel-group, feasibility study to assess the acceptability and preliminary impact of family navigation plus usual care versus usual care on attrition in managing pediatric obesity: a study protocol

BackgroundPediatric obesity management can be successful, but some families discontinue care prematurely (i.e., attrition), limiting treatment impact. Attrition is often a consequence of barriers and constraints that limit families’ access to obesity management. Family Navigation (FN) can improve access, satisfaction with care, and treatment outcomes in diverse areas of healthcare. To help our team prepare for a future effectiveness trial, the objectives of our randomized feasibility study are to (i) explore children’s and caregivers’ acceptability of FN and (ii) examine attrition, measures of study rigor and conduct, and responses to FN + Usual Care vs Usual Care by collecting clinical, health services, and health economic data.MethodsIn our 2.5-year study, 108 6–17-year-olds with obesity and their caregivers will be randomized (1:1) to FN + Usual Care or Usual Care after they enroll in obesity management clinics in Calgary and Mississauga, Canada. Our Stakeholder Steering Committee and research team will use Experience-Based Co-Design to design and refine our FN intervention to reduce families’ barriers to care, maximizing the intervention dose families receive. FN will be delivered by a navigator at each site who will use logistical and relational strategies to enhance access to care, supplementing obesity management. Usual Care will be offered similarly at both clinics, adhering to expert guidelines. At enrollment, families will complete a multidisciplinary assessment, then meet regularly with a multidisciplinary team of clinicians for obesity management. Over 12 months, both FN and Usual Care will be delivered virtually and/or in-person, pandemic permitting. Data will be collected at 0, 3, 6, and 12 months post-baseline. We will explore child and caregiver perceptions of FN acceptability as well as evaluate attrition, recruitment, enrolment, randomization, and protocol integrity against pre-set success thresholds. Data on clinical, health services, and health economic outcomes will be collected using established protocols. Qualitative data analysis will apply thematic analysis; quantitative data analysis will be descriptive.DiscussionOur trial will assess the feasibility of FN to address attrition in managing pediatric obesity. Study data will inform a future effectiveness trial, which will be designed to test whether FN reduces attrition.Trial registrationThis trial was registered prospectively at ClinicalTrials.gov (#NCT05403658; first posted: June 3, 2022).

AI-based chatbot micro-intervention for parents: Meaningful engagement, learning, and efficacy.

Mental health issues have been on the rise among children and adolescents, and digital parenting programs have shown promising outcomes. However, there is limited research on the potential efficacy of utilizing chatbots to promote parental skills. This study aimed to understand whether parents learn from a parenting chatbot micro intervention, to assess the overall efficacy of the intervention, and to explore the user characteristics of the participants, including parental busyness, assumptions about parenting, and qualitative engagement with the chatbot. A sample of 170 parents with at least one child between 2-11 years old were recruited. A randomized control trial was conducted. Participants in the experimental group accessed a 15-min intervention that taught how to utilize positive attention and praise to promote positive behaviors in their children, while the control group remained on a waiting list. Results showed that participants engaged with a brief AI-based chatbot intervention and were able to learn effective praising skills. Although scores moved in the expected direction, there were no significant differences by condition in the praising knowledge reported by parents, perceived changes in disruptive behaviors, or parenting self-efficacy, from pre-intervention to 24-hour follow-up. The results provided insight to understand how parents engaged with the chatbot and suggests that, in general, brief, self-guided, digital interventions can promote learning in parents. It is possible that a higher dose of intervention may be needed to obtain a therapeutic change in parents. Further research implications on chatbots for parenting skills are discussed.

Effectiveness of Motivational Interviewing in Increasing Use of Hearing Protection Devices Among Agricultural Producers.

Agricultural producers are frequently exposed to noise that is hazardous to their hearing and cardiovascular health, and have among the highest rates of noise-induced hearing loss of all occupations. However, despite information-sharing approaches, few producers wear sufficient hearing protection. There is a need to develop effective methods of protecting producers from their noise exposure. We provided a series of 2 to 3 short (30-minute) telephone-based motivational interviewing (MI) sessions to noise-exposed agricultural producers. We assessed intervention effectiveness through changes in measuring hearing protector use pre- and post-intervention using a one-group pre/posttest design. The sample (N = 29) predominantly consisted of crop producers from Michigan. The mean percentage of time hearing protection was used increased from 44.9% to 51.8% after the intervention, approximately a 7% increase (p =.105). Regression analysis suggested the relationship between intervention dose and use of hearing protection was not correlative. There was a marginal increase in the use of hearing protection after the intervention, although setting-specific increases in use were uneven. Intervention dose did not correlate with a change in hearing protection use. Further research is warranted to determine the effectiveness of MI, how it compares to information sharing, and to identify intervention dose parameters that promote efficiency.

Effects of Oleanolic Acid on Myocardial Injury in Diabetic Mice by Regulating Phosphatidylinositol 3 Kinase/Protein Kinase B/Glucose Transporter Type 4 Signalling Pathway

One of the leading causes of diabetes-related deaths is myocardial damage, which may be the cause of heart failure in people with type 2 diabetes mellitus. The objective of the research was to look at the impact of coronary failure with kind a pair of type 2 diabetes mellitus. This project aimed to explore the protective impact of oleanolic acid on myocardial damage in type 2 diabetes mellitus and to investigate the connected mechanism. Specific pathogen free grade db/db male mice were elected as model, while the Db/m mice were opted for control. Different doses of drug intervention were performed and the general condition, cardiac function, blood glucose, blood lipids, degree of myocardial injury, and degree of oxidative stress were examined by morphological examination of myocardial tissues, biochemical examination, and gene and protein amount detection. The results showed that lactate dehydrogenase, creatine kinase isoenzyme, total cholesterol, triglycerides and malondialdehyde levels in serum of Db/db mice were increased, while phosphatidylinositol 3 kinase, protein kinase B, glucose transporter 4 expression and superoxide dismutase level in myocardial tissue were decreased. After using oleanolic acid, the serum concentrations of lactate dehydrogenase, creatine kinase isoenzyme, total cholesterol, triglycerides and malondialdehyde were declined in Db/db mice, while phosphatidylinositol 3 kinase, protein kinase B, glucose transporter 4 expression and superoxide dismutase level were rised. The results recommend that oleanolic acid has protective impact on cardiac muscle injury in Db/db mice and conjointly the mechanism could also be correlated with promoting the activation of phosphatidylinositol 3 kinase/protein kinase B/glucose transporter 4 signal transduction.

Comparative Study of the Effect of Vaginal use of Primrose Oil with Misoprostol on Cervical Preparation of Prim Gravid Women: A Double-blind Clinical Trial.

This study compares the effect of vaginal administration of evening primrose oil with misoprostol on cervical preparation in prim gravid women at ≥40 weeks gestation. This was a double-blind randomized clinical trial conducted in Isfahan, Iran during 2019-2020 on 110 prim gravid pregnant women with a gestational age of 40 weeks and more and cephalic presentation of the fetus with the obstetrical indication for pregnancy termination. After obstetric examinations to rule out cephalo pelvic disproportion and calculation of the Bishop score by the researcher, patients were randomized to receive 25 μg misoprostol tablets (n = 55) or 1000 mg evening primrose oil Pearls (n = 55) administrated vaginally by a midwife. We compared Bishop's score before and after the intervention, time of cervical ripening, a dose of intervention for cervical ripening, need to induce labor, the interval between cervical preparation and induction of labor, duration of oxytocin use, need for cesarean section, and its cause, Apgar score at 5 and 10 minutes, neonatal birth weight. Mean baseline Bishop Score was not significant between the groups (P = 0.45); after the intervention, it was significantly higher in the primrose oil group (P < .001). Significantly fewer patients required cesarean sections in the primrose oil group (P = 0.03). The other outcomes were. not significant between the groups (P > 0.05). Misoprostol and primrose oil administration appear to positively affect cervical readiness. Primrose oil resulted in significantly better Bishop Scores and fewer cesarean sections compared to misoprostol in pregnancy 40 weeks and more.

The effect of 6-week consumption of bakery products on changes in selected anthropometric parameters in women.

The changes in consumers' eating habits are one of the most important factors affecting the consumption of selected foods. The most important factors for bakery products consumers are freshness, taste, price, durability, composition, and country of origin. The aim of this study was to monitor changes in selected anthropometric characteristics in women from the general population in Slovakia, after 6 weeks of bakery products consumption. The study was conducted on healthy adult women from the general population (n=78), who were divided into four subgroups ("gluten" group, "gluten-free" group, "whole-grain" group and "control" group). The intervention dose consisted of a different combination of several types of bakery products (bread, pastries, soft pastries) within the individual weeks of consumption, while the intervention lasted 6 weeks, women consumed 150-200 grams per day. Anthropometric characteristics were measured by body composition analyser InBody 720 (Biospace Co. Ltd., Seoul, Republic of Korea), which works on the principle of bioelectrical impedance analysis. We also used the Lookin´Body 3.0 software to process the results. The collected data from these measurements were evaluated statistically and graphically in Microsoft Office Excel 2010 (Los Angeles, CA, USA). The levels of statistical significance were set at P<0.05 (*); P<0.01 (**); P<0.001 (***). Differences among subgroups of probands were tested with Pared Student t-test. The amount of fat mass (FM) in the participants changed along a similar curve as their body weight. After the 6-week intervention, there was a slight decrease in FM with statistical significance (P<0.01). In the third measurement, i.e., two months after the intervention, there was an increase in the amount of FM, but without statistical significance. Fat free mass (FFM) values in women increased very slightly after 6 weeks of consumption and remained approximately at the same level two months after the intervention (without statistical significance). We noted the most significant changes in the visceral fat area (VFA) parameter, which had a steadily increasing tendency. Changes in VFA values were statistically significant after the 6-week intervention (P<0.01) and also after two months of the intervention (P<0.05). Changes in body composition in women were noted already after 6 weeks of bakery products consumption, especially in the FM, FFM, VFA and partially BMI parameters, but no changes were recorded in the WHR parameters during the entire duration of the study. One of the most significant results is the finding that there was an increase in VFA when consuming all types of bakery products (gluten, gluten-free and whole grain).

The gestational diabetes future diabetes prevention study (GODDESS): A partially randomised feasibility controlled trial.

To assess the feasibility of an ante- and post-natal lifestyle intervention for women with gestational diabetes mellitus (GDM) to reduce type 2 diabetes risk. A partially randomised patient preference feasibility trial. Diabetes antenatal clinics in two inner-London hospitals, UK. Pregnant women ≥18 years with a GDM diagnosis and pre-pregnancy body mass index of ≥25kg/m2. Participants in the intervention group were offered four motivational interview-based sessions (two antenatally and two postnatally, at 3 and 6 months postpartum), a WhatsApp support group, a FitBit and electronic self-help resources. Recruitment; retention; intervention dose received; data completion; adaptions; proportion achieving ≥5% weight loss; weight change, blood glucose; blood pressure; diet, physical activity, breastfeeding and depression. Clinical outcomes were measured at baseline and 6 months postpartum. 50 participants were recruited from 155 eligible women (32% recruitment rate). Thirty-four were recruited to the intervention group (23 following randomisation (RI-group) and 11 based on preference (PI-group)); and 16 to the control group (13 randomised (RC-group) and 3 preference (PC-group)). Attrition was 44% (n = 22/50). Forty-six percent (n = 6) of the intervention group (25% (n = 2) of the RI-group and 80% (n = 4) of the PI-group) achieved ≥5% weight loss compared to 8% (n = 1) in the control group (95% confidence interval (CI) -0.69 to 0.07). Mean weight change was -2.1kg±9.0 in the intervention group (0kg±5.4 in the RI-group and -5.4kg±13.0 in the PI-group) compared to +4.4kg±4.9 in the control group (RC +4.4kg ±5.3 and PC +4.7kg ±3.1, 95% CI -12.4 to 0.2). Recruitment was feasible, but strategies to improve retention are needed. The findings suggest the intervention can support women with GDM to lose weight. The observed weight loss was primarily in women who preferred the intervention. Therefore, future trials may need to adopt a preference design and consider factors associated with preference. Trial registration: ISRCTN52675820 https://www.isrctn.com/ISRCTN52675820?q=ISRCTN52675820&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search.

Investigation of the Utility of Multivariate Meta-Analysis Methods in Estimating the Summary Dose Response Curve.

Traditional meta-analyses often assess the effectiveness of different doses of the same intervention separately or examine the overall differences between intervention and placebo groups. The present study aimed to model the effect sizes obtained from different doses in multiple studies using a two-stage dose-response meta-analytic approach while taking dose variations into account. Different dose-response meta-analysis models using linear, quadratic, and restricted cubic spline (RCS) functions were fitted. A two-stage approach utilizing multivariate meta-analysis was performed and the obtained results were compared with those of the univariate meta-analysis. A random effect dose-response meta-analysis was performed using data from an existing systematic review on combination therapy with zonisamide and anti-Parkinson drugs for Parkinson's disease. The effective or optimum dose for producing maximum response was also investigated. Moreover, a sensitivity analysis was performed by changing the knots of the RCS model. Dose-response meta-analysis was performed using data from four double-blinded randomized controlled trials with 724 and 309 patients with Parkinson's disease in dose and placebo arms, respectively. The quadratic model yielded the smallest Akaike information criterion (AIC), compared to the linear and RCS models, indicating it to be the best fit for the data. Compared to the traditional approach, the two-stage approach could model the dose-dependent effect of zonisamide on the Unified Parkinson's Disease Rating Scale (UPRDS) part III score and predict the outcome for different doses through a single analysis.

Efficacy of Different Dosing Regimens of IgE Targeted Biologic Omalizumab for Chronic Spontaneous Urticaria in Adult and Pediatric Populations: A Meta-Analysis.

Chronic urticaria is a debilitating skin condition that is defined as itchy hives at least twice a week and lasting for six or more weeks, with or without angioedema. Chronic spontaneous urticaria (CSU) is a form of disease that is witnessed in two-thirds of those with chronic urticaria. This meta-analysis explores the efficacy of differential dosages of omalizumab for outcomes of weekly itching scores, weekly wheal scores, urticarial assessment score 7 (UAS7), and responder rates. Adhering to PRISMA Statement 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Embase, and Web of Science was conducted until 15 September 2022. A combination of the following keywords was used: omalizumab and chronic urticaria. Data comprising clinical trial ID, name, author/year, country, dosage and time of intervention, inclusion criteria, mean age, female gender, and racial grouping information were obtained. The meta-analytical outcomes were analyzed in RevMan 5.4. The risk-of-bias assessment was conducted using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). A total of 10 trials comprising 1705 patients with CSU were included. Notably, 1162 belonged to the intervention group, while 543 were controls. A total of 70.4% of the participants were female in the intervention group, while 65.6% of them were female in the control group. The overall mean age was 38.64 ± 10.66 years. Weekly itch score outcomes were most notable with 150 mg dosage (Cohen's d = -2.6, 95% CI = -4.75, -0.46, p = 0.02). The weekly wheal score outcomes had the largest effect size with 300 mg dosage (Cohen's d = -1.45, 95% CI = -2.2, -0.69, p = 0.0002). For UAS7 outcomes, the largest effect size was yielded with 150 mg dosage (Cohen's d = -6.92, 95% CI: -10.38, -3.47, p &lt; 0.0001). The response rate to omalizumab had a likelihood of being higher with 300 mg of intervention compared to placebo (OR = 8.65, 95% CI = 4.42, 16.93, p &lt; 0.0001). Well-rounded urticarial symptom resolution was observed with 150 mg and 300 mg dosages of omalizumab. Improvement of UAS7 was more comparable with 150 mg dosage, whereas the chance of response to treatment was higher with 300 mg dosage. Our findings support omalizumab as an effective intervention for adult and pediatric populations that are resistant to many therapies, including high-dose H1-antihistamines.