Intervention Dose Research Articles

Ginger intervention on body weight and body composition in adults: a GRADE-assessed systematic review and dose-response meta-analysis of 27 randomized controlled trials.

Ginger consumption may have an inverse relationship with obesity and metabolic syndrome parameters; however, clinical trials have reported contradictory results. To systematically review and analyze randomized controlled trials (RCTs) assessing the effects of ginger on body weight and body composition parameters. Databases were searched for appropriate articles up to August 20, 2022. All selected RCTs investigated the impact of ginger on glycemic indices in adults. A random effects model was used to conduct a meta-analysis, and heterogeneity was assessed using the I2 statistic. Net changes in body weight, body mass index (BMI), waist circumference (WC), and percent body fat were used to calculate the effect size, which was reported as a weighted mean difference (WMD) and 95% confidence intervals (CIs). The risk of bias was assessed. A total of 27 RCTs involving 1309 participants were included. The certainty in the evidence was very low for WC and BMI, and low for body weight and percent body fat as assessed by the GRADE evidence profiles. The meta-analysis showed a significant association between ginger supplementation and a reduction in body weight (WMD, -1.52 kg; 95%CI, -2.37, -0.66; P < 0.001), BMI (WMD, -0.58 kg/m2; 95%CI, -0.87, -0.30; P < 0.001), WC (WMD, -1.04 cm; 95%CI: -1.93, -0.15; P = 0.021), and percent body fat consumption (WMD, -0.87%; 95%CI, -1.71, -0.03; P = 0.042). The results of the nonlinear dose-response analysis showed a significant association between the ginger dose with body weight (Pnonlinearity = 0.019) and WC (Pnonlinearity = 0.042). The effective dose of ginger intervention for body mass reduction was determined to be 2 g/d in dose-response analysis. The duration of ginger intervention had a significant nonlinear relationship with body weight (Pnonlinearity = 0.028) with an effective duration of longer than 8 weeks. Our findings provide evidence that ginger consumption may significantly affect body composition parameters nonlinearly. More, well-constructed RCTs are needed.

Improving 5th Grade Mathematics Knowledge with Worked Examples and Self-Explanation Prompts

Prior short-term studies have shown the effectiveness of worked examples and self-explanation prompts in improving elementary students’ mathematics knowledge. However, year-long classroom-based interventions have been tested only with older students. The purpose of the current study was to explore the effectiveness of a year-long classroom intervention, MathByExample, which paired worked examples and self-explanation prompts with practice problems. We utilized a classroom-based experimental design where 5th-grade classrooms were randomly assigned to one of two conditions. Findings illustrate that intervention dosage impacts the effectiveness of the intervention in improving 5th graders’ grade-level mathematics knowledge. In addition, prior knowledge impacted the effectiveness of the intervention for two of the four outcome variables. This study expands the literature on the use of worked examples and self-explanation prompts in several ways. It provides evidence that this tool has the potential to improve elementary students’ learning. It included four different measures of math knowledge, which provides stronger support for the effectiveness of the intervention. Finally, it adds to the literature that shows the benefits of studying and explaining both correct and incorrect worked examples.

Computer-assisted instruction for transparent language reading for K-3 learners with intellectual, developmental and learning disabilities: a systematic review with meta-analysis

PurposeComputer-assisted instruction (CAI) has been used to combat reading challenges, namely reading accuracy and rate for learners with intellectual, developmental and learning disabilities (IDLD). Whilst most reading CAI effectiveness has been studied in English, other transparent languages have less evidence. This study provides a systematic review and meta-analysis of CAI effectiveness for transparent language reading for K-3 learners with IDLD.Design/methodology/approachThis study systematically reviews academic peer-reviewed studies from 2010 to 2023 with either randomised controlled treatment (RCT) or single-case treatments. Articles were searched from the ACM Digital Library, Google Scholar, IEEE Xplore, ERIC, PsychINFO and Science Direct databases, references and systematic review articles. Reading component skills effect sizes were computed using the random effect sizes model.Findings11 RCT studies of reading CAI for transparent languages with 510 learners with IDLD were found. A random effect sizes (Cohen’s d) of CAI on individual reading component skills were d = 0.24, p-value = 0.063 and confidence interval (CI) 95% (−0.068–0.551) for phonics and phonemic awareness d = 0.41, p-value = 0.000 and CI 95% (0.175–0.644). Given an average intervention dosage of 1.8 h weekly for a maximum of 16 weeks, CAI had better retention with d = 1.13, p-value = 0.066 and CI 95%(−0.339–2.588). However, these results must be interpreted with a concern of only using published studies.Originality/valueThe study contributes to quantitative CAI effectiveness for transparent language reading components for learners with IDLD.

Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial

Linaclotide, a guanylate cyclase C agonist, has been approved in the USA for the treatment of chronic idiopathic constipation and irritable bowel syndrome with predominant constipation in adults. We aimed to assess the efficacy and safety of linaclotide in paediatric patients aged 6-17 years with functional constipation. This randomised, double-blind, placebo-controlled, multicentre, phase 3 study was done at 64 clinic or hospital sites in seven countries (USA, Canada, Israel, Italy, the Netherlands, Ukraine, and Estonia). Patients aged 6-17 years who met modified Rome III criteria for functional constipation were randomly assigned (1:1), with a block size of four and stratified by age (6-11 years and 12-17 years), to receive either oral linaclotide 72 μg or placebo once daily for 12 weeks. Participants, investigators, and data assessors were masked to assignment. The primary efficacy endpoint was change from baseline (CFB) in the 12-week frequency rate of spontaneous bowel movements (SBMs; occurring in the absence of rescue medication on the calendar day of or before the bowel movement) per week and the secondary efficacy endpoint was CFB in stool consistency over the 12-week treatment period; efficacy and safety were analysed in all patients in the randomised population who received at least one dose of study intervention (modified intention-to-treat population and safety population, respectively). The study is registered with ClinicalTrials.gov, NCT04026113, and the functional constipation part of the study is complete. Between Oct 1, 2019, and March 21, 2022, 330 patients were enrolled and randomly assigned to linaclotide (n=166) or placebo (n=164). Two patients in the linaclotide group did not receive any treatment; thus, efficacy and safety endpoints were assessed in 328 patients (164 patients in each group). 293 (89%) patients completed the 12-week treatment period (148 in the linaclotide group and 145 in the placebo group). 181 (55%) of 328 patients were female and 147 (45%) were male. At baseline, the mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) for placebo and 1·16 SBMs per week (0·83) for linaclotide, increasing to 2·29 SBMs per week (1·99) for placebo and 3·41 SBMs per week (2·76) for linaclotide during intervention. Compared with placebo (least-squares mean [LSM] CFB 1·05 SBMs per week [SE 0·19]), patients treated with linaclotide showed significant improvement in SBM frequency (LSM CFB 2·22 SBMs per week [0·19]; LSM CFB difference 1·17 SBMs per week [95% CI 0·65-1·69]; p<0·0001). Linaclotide also significantly improved stool consistency over placebo (LSM CFB 1·11 [SE 0·08] vs 0·69 [0·08]; LSM CFB difference 0·42 [95% CI 0·21-0·64]; p=0·0001). The most reported treatment-emergent adverse event (TEAE) by patients treated with linaclotide was diarrhoea (seven [4%] of 164 vs three [2%] of 164 patients in the placebo group) and by patients treated with placebo was COVID-19 (five [3%] vs four [2%] in the linaclotide group). The most frequent treatment-related TEAE was diarrhoea (linaclotide: six [4%] patients; placebo: two [1%] patients). One serious adverse event of special interest (treatment-related severe diarrhoea resulting in dehydration and hospitalisation) occurred in a female patient aged 17 years in the linaclotide group; this case resolved without sequelae after administration of intravenous fluids. No deaths occurred during the study. Linaclotide is an efficacious and well tolerated treatment for functional constipation in paediatric patients and has subsequently been approved by the US Food and Drug Administration for this indication. AbbVie and Ironwood Pharmaceuticals.

The effect of acarbose on inflammatory cytokines and adipokines in adults: a systematic review and meta-analysis of randomized clinical trials.

Although a large number of trials have observed an anti-inflammatory property of acarbose, the currently available research remains controversial regarding its beneficial health effects. Hence, the purpose of this study was to examine the effect of acarbose on inflammatory cytokines and adipokines in adults. PubMed, Web of Science, and Scopus were systematically searched until April 2023 using relevant keywords. The mean difference (MD) of any effect was calculated using a random-effects model. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated via the random-effects model. The current meta-analysis of data comprised a total of 19 RCTs. Meta-analysis showed that acarbose significantly decreased tumor necrosis factor-alpha (TNF-α) (weighted mean difference [WMD]) = -4.16 pg/ml, 95% confidence interval (CI) -6.58, -1.74; P = 0.001) while increasing adiponectin (WMD = 0.79 ng/ml, 95% CI 0.02, 1.55; P = 0.044). However, the effects of acarbose on TNF-α concentrations were observed in studies with intervention doses ≥ 300 mg/d (WMD = -4.09; 95% CI -7.00, -1.18; P = 0.006), and the adiponectin concentrations were significantly higher (WMD = 1.03 ng/ml, 95%CI 0.19, 1.87; P = 0.016) in studies in which the duration of intervention was less than 24 weeks. No significant effect was seen for C-reactive protein (CRP; P = 0.134), interleukin-6 (IL-6; P = 0.204), and leptin (P = 0.576). Acarbose had beneficial effects on reducing inflammation and increasing adiponectin. In this way, it may prevent the development of chronic diseases related to inflammation. However, more studies are needed.

Family Involvement in Elementary Reading Intervention: Compensatory Relations to Dosage and Tutor-Level Heterogeneity

We used triannual reading curriculum-based measurement of oral reading fluency data from 11,834 U.S. students in Grades 2 and 3 enrolled in an evidence-based Tier 2 reading intervention program (Reading Corps) to investigate the extent to which family involvement in the intervention might buffer against a negative effect of lower intervention dosage. The relation between family involvement in Reading Corps and growth in oral reading fluency was stronger when students spent fewer hours in tutoring, suggesting that family involvement in tiered reading intervention can compensate for receiving less intervention dosage. There was noticeable variation in this effect across tutors, suggestive of tutor-level heterogeneity of this relation. The relation between sending family engagement materials to families and the materials that are returned to tutors also substantially varied across tutors. We discuss findings in terms practical significance for school-based academic intervention systems. We highlight limitations and opportunities for future directions as well.

The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice

Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits of lactate, the by-product of exercise, in various aspects of brain function and disorders. However, there remains a gap in understanding the effects of lactate dosage and its impact on aged rodents. The present study first examined the long-term effects of three different doses of lactate intervention (2000 mg/kg, 1000 mg/kg, and 500 mg/kg) and high-intensity interval training (HIIT) on aging mice (20–22 months) as the 1st experiment. Subsequently, in the 2nd experiment, we investigated the long-term effects of 500 mg/kg lactate intervention and HIIT on brain neuroplasticity in aged mice (25–27 months).The results of the 1st experiment demonstrated that both HIIT and different doses of lactate intervention (500 mg/kg and 2000 mg/kg) positively impacted the neuroplasticity biomarker VEGF in the hippocampus of aging mice. Subsequently, the 2nd experiment revealed that long-term HIIT significantly improved the performance of mice in open-field, novel object recognition, and passive avoidance tests. However, lactate intervention did not significantly affect these behavioral tests. Moreover, compared to the control group, both HIIT and lactate intervention positively influenced the angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial biomarker (SDHA), and metabolic protein (p/t-CREB, p/t-HSL, and LDH) in the hippocampus of aged mice. Notably, only lactate intervention significantly elevated the BDNF (PGC-1α, SIRT1, and BDNF) signaling pathway and metabolic content (lactate and pyruvate). In the end, long-term HIIT and lactate intervention failed to change the protein expression of p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 and Pan Lactic aid-Lysine in the hippocampus of aged mice.In summary, the present study proved that long-term HIIT and lactate treatment have positive effects on the brain functions of aged mice, suggesting the potential usage of lactate as a therapeutic strategy in neurodegenerative diseases in the elderly population.

BCL11A-related intellectual developmental disorder; intervention dosage; gray-matter volume

BCL11A-related intellectual developmental disorder; intervention dosage; gray-matter volume

Behavioral Interventions to Improve Sleep Outcomes in Individuals With Multiple Sclerosis: A Systematic Review.

Sleep disturbances are common in individuals with multiple sclerosis. The objective of this systematic review was to determine effective behavioral interventions to improve their sleep. Literature searches were performed in December 2021 in Ovid MEDLINE, Elsevier Embase, and Web of Science, along with hand searching for grey literature and cited references. Four reviewers independently reviewed titles and abstracts (2 reviewers for each article; n = 830) and the full-text articles (n = 81). Consensus for inclusion was achieved by a fifth reviewer. Thirty-seven articles were eligible for inclusion. Four reviewers extracted relevant data from each study (2 reviewers for each article) using a standard data extraction table. Consensus was achieved for completeness and accuracy of the data extraction table by a fifth reviewer. The same 4 reviewers conducted a quality appraisal of each article to assess the risk of bias and quality of the articles, and consensus was achieved by a fifth reviewer as needed. Descriptive data were used for types of interventions, sleep outcomes, results, and key components across interventions. Overall, the cognitive behavioral therapy for insomnia, cognitive behavioral therapy/psychotherapy, and education/self-management support interventions reported positive improvements in sleep outcomes. Quality appraisal scores ranged from low to high, indicating potential for bias. Variability in the intervention type, intervention dose, outcomes used, training/expertise of interventionist, specific sample, and study quality made it difficult to compare and synthesize results. Further research is necessary to demonstrate the efficacy of most of the interventions.

Experiences of physiotherapists considering virtual reality for shoulder rehabilitation: A focus group study.

Shoulder pain is common and associated with substantial morbidity. Different treatment strategies are being prescribed with equivocal results. Virtual reality (VR) is a novel technology and emerging research suggests that VR may be a promising alternative to current treatments. Prior to effectiveness research or any large-scale introduction, VR-applications require appropriate scrutiny including feasibility- and acceptability of clinicians and patients. Therefore, the aim of this study was to collect experiences of physiotherapists after using immersive VR. A qualitative interpretive design was used to explore physiotherapists' experiences related to the use of VR for people with shoulder symptoms. 17 physiotherapists were asked to use VR at home for five days prior to a focus group interview. Data from the focus group interviews were analyzed using a six-phase process of thematic analysis. Three main themes were identified, each divided into subthemes. The main themes were: 1. VR as an extension of contemporary physiotherapy care: physiotherapists were positive about the potential of VR and its applicability in daily care. 2. Physiotherapist uncertainties of future care using VR: participants expressed concerns about their professional identity, particularly as patients engage in independent home exercises. 3. Physiotherapist's requirements for implementation of VR: participants shared their needs for evidence regarding the effectiveness and parameters such as frequency, dosage and intensity of the VR intervention. Physiotherapists were positive about VR as an intervention tool. However, they felt more knowledge is needed about parameters of VR. The findings of this study inform researchers and technology developers about optimal design of interventions and applications using VR.

Amelioration of Oxidative Stress in Rats with Chronic Obstructive Pulmonary Disease through Shenqi Huatan Decoction Activation of Peroxisome Proliferator‐Activated Receptor Gamma‐Mediated Activated Protein Kinase/Forkhead Transcription Factor O3a Signaling Pathway

Background. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. Currently, no specific treatment strategy has been established; therefore, finding new treatment methods is essential. Clinically, Shenqi Huatan Decoction (SQHT) is a traditional Chinese medicinal formula for COPD treatment; however, its mechanism of action in treatment needs to be clarified. Methods. The COPD rat model was replicated by cigarette smoking and tracheal injection using the LPS method. The control group and the SQHT groups were treated with dexamethasone and SQHT by gavage, respectively. After treatment, superoxide dismutase (SOD) serum levels, total antioxidant capacity (TAOC), lipid peroxidation, and malondialdehyde (MDA) were detected by enzyme‐linked immunosorbent assay (ELISA). Activated protein kinase alpha (AMPK‐α), forkhead transcription factor O3a (FOXO3a), manganese SOD (MnSOD), and peroxisome proliferator‐activated receptor gamma (PPARγ) were detected using reverse transcriptase quantitative polymerase chain reaction (RT‐qPCR) and Western blot. Microribonucleic acid and protein expression levels were measured, and pathological changes in lung tissue were observed using hematoxylin and eosin staining. Results. The pathological findings suggested that SQHT substantially affects COPD treatment by enhancing alveolar fusion and reducing emphysema. ELISA results showed that SQHT could lower the blood levels of MDA and lipid peroxide and raise SOD and TAOC levels, suggesting that it could lessen oxidative stress. In the lung tissue of rats with COPD, large doses of SQHT intervention dramatically increased AMPK protein expression, AMPK‐α, FOXO3a, MnSOD, and PPARγ, indicating that SQHT may reduce oxidative stress by activating the PPARγ‐mediated AMPK/FOXO3a signaling pathway. Similar results were obtained using RT‐qPCR. Conclusion. SQHT is effective for COPD treatment. The mechanism of action may be related to the activation of the PPARγ‐mediated AMPK/FOXO3a signaling pathway to improve oxidative stress in lung tissue.

Atorvastatin inhibits Lipopolysaccharide (LPS)-induced vascular inflammation to protect endothelium by inducing Heme Oxygenase-1 (HO-1) expression.

This study aimed to explore the differential effects of varying doses of atorvastatin on antagonizing lipopolysaccharide (LPS)-induced endothelial inflammation based on heme oxygenase 1 (HO-1) expression. Vascular endothelial inflammatory injury was induced in 40 Sprague-Dawley rats by intraperitoneal injection of LPS. These rats were randomly divided into control, low-dose atorvastatin, high-dose atorvastatin, and HO-1 blocking groups. Seven days after treatment, all rats were sacrificed, and heart-derived peripheral blood was collected to measure the serum concentrations of bilirubin, alanine aminotransferase (ALT), total cholesterol, malondialdehyde, endothelial cell protein C receptor, endothelin-1, von Willebrand factor, and soluble thrombomodulin. Meanwhile, the number of circulating endothelial cells was determined using flow cytometry. Vascular tissues from descending aorta of rats from each group were extracted to detect the expression level of HO-1. After different doses of atorvastatin intervention, the above inflammatory indices were decreased, and HO-1 expression and ALT concentration were increased in the atorvastatin-treated group of rats compared with the control group. These changes were more pronounced in the high-dose statin group (P < 0.05). Conversely, no significant decrease in the above inflammatory indices and no significant increase in HO-1 expression were observed in rats in the blocking group (P > 0.05). For LPS-induced vascular inflammation, high-dose atorvastatin exerts potent anti-inflammatory and vascular endothelial protection effects by inducing HO-1 expression.

The Effect of Various Types of Exercise on Gut Microbiota: A Systematic Review

Objective: Gut microbiota composition plays a pivotal role in health and emerging evidence supports the ability of exercise training programs to alter the gut microbiota’s composition and function, which could counteract dysbiosis and the effects of chronic diseases. This study aims to investigate the effectiveness of different exercise methods on the composition of intestinal microbiota. Methods: We searched for published peer-reviewed articles in PubMed and Google Scholar databases up until January 2023. We searched using the terms "exercise", "education", "microbiome" and "microbiota". Results: By electronic search until January 2023 in the databases with keywords made in Mesh by mentioning Title/Abstract, several 1814 articles were collected. By repeating and performing filtering at each stage, 15 clinical trials were finally left in the study. The results showed varying degrees of efficacy and high inter-individual variations. In conclusion, the baseline microbiome profile was shown to have a decisive role in microbiome responsiveness to training intervention and training dose and duration seem to be a determining factor in all exercise modalities. Conclusion: In general, can be said that exercise can balance GM. More importantly, exercise is proposed to present a stressor to the gut that stimulates beneficial adaptations and improves long-term gut barrier flexibility over time through regular physical activity. It seems that the GM changes caused by aerobic exercise are reversible after returning to a sedentary lifestyle. Therefore, it is recommended that exercise initially causes a disrupts in GM that, with continued exercise and thus adaptation, revenues to the pre-exercise state.

Global research hotspots and trends in constraint-induced movement therapy in rehabilitation over the past 30 years: a bibliometric and visualization study.

Stroke is a cerebrovascular disease with high prevalence and mortality, and upper limb hemiparesis is a major factor limiting functional recovery in stroke patients. Improvement of motor function in stroke patients through various forms of constraint-induced movement therapy (CITM) has been recognized as safe and effective in recent years. This research field lacks a comprehensive systematic and clear vein combing analysis, analyzing the literature research of CIMT in the field of rehabilitation in the past three decades, summarizing the research hotspots and cutting-edge trends in this field, in an effort to offer ideas and references for subsequent researchers. Relevant literature on CIMT in rehabilitation was collected from 1996 to 2024 within the Web of Science database's core dataset by using CiteSpace6.1, VOSviewer1.6.18, R-bibliometrix4.6.1, Pajek5.16, Scimago Graphica 1.0.26 software for visualization and analysis. There were 970 papers in all United States was ranked first with 401 papers. Alabama Univ was ranked first for institutions with 53 papers. Neurorehabilitation and Neural Repair was ranked first for journals with 78 papers, and Taub E was ranked first for author publications with 64 papers. Research keywords were CIMT, stroke rehabilitation, upper extremity function, lower extremity gait balance, randomized controlled trials, physical therapy techniques (transcranial magnetic stimulation and sensory amplitude electrical stimulation), primary motor cortex plasticity, lateral dominance (spatial behaviors), cerebral vascular accidents, activities of daily living, hand function, disability, functional restoration, bimanual training, aphasia, acquired invalidity, type A Botulinum toxin and joystick riding toys. The current state of research shows that CIMT still has a vast potential for development in the field of rehabilitation research. The research hotspots are the clinical efficacy of CIMT combined with other therapies (botulinum toxin type A, transcranial direct current stimulation, virtual reality, mirror therapy, robotic-assisted) to enhance the functionality of upper limb hemiparesis in stroke patients, the mechanism of CIMT to improve the plasticity of the motor cortex through electrophysiological and imaging methods, and improvement of lower limb gait balance function in stroke patients and aphasia applications, the optimal intervention time and dose, and exploration of CIMT in new settings such as robot-assisted, telemedicine, and home rehabilitation.

Family responsive care mediating the home visiting effects on left-behind children's early development in rural China.

The early development of left-behind children requires great concern and improvement. Yet, current interventions for left-behind children are mainly focussed on children older than 3. This study aims to assess the effectiveness of a home visiting programme on family responsive care and early development of rural left-behind children and examine whether family responsive care mediates the effects of intervention on child development. A quasi-experimental study design was utilized in this study. A stratified clustered sampling was employed to choose villages in programme towns into intervention group. A control village was matched with every intervention village. All of the left-behind children and their caregivers meeting the inclusion criteria in the chosen villages were enrolled in the survey. The outcomes included child development, caregiver's early stimulation, parent-child communication, and learning materials. Baseline assessments were conducted in 2018, and endline assessments were conducted in 2020. In the endline survey, we enrolled 608 children with 258 in the intervention group and 350 in the control group. Left-behind children in the intervention group were less likely to have development delay compared with the control group (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.36, 0.96). Migrant parents of children in the intervention group showed higher proportion of expressing emotional support to their children when communicating (OR = 1.69, 95% CI: 1.05, 2.72). Children who received home visits more than once per 2months had lower level of suspected development delay than children in the control group (OR = 0.34, 95% CI: 0.18, 0.68). Caregiver's early stimulation and migrant parents' emotional support to left-behind children mediated the intervention dose and left-behind children's development. Caregiver's early stimulation mediates the intervention and child's development. The findings suggest a promising future for scaling similar early childhood development interventions for left-behind children in rural settings.

Evaluation of adapted parent training for challenging behaviour in pre-school children with moderate to severe intellectual developmental disabilities: A randomised controlled trial.

There is limited evidence on the effectiveness of parenting interventions to improve disruptive behaviour in children with intellectual developmental disabilities. This clinical trial evaluated whether an adapted group parenting intervention for preschool children with intellectual developmental disabilities who display challenging behaviour is superior to treatment as usual in England. 261 children aged 30-59 months with moderate to severe intellectual developmental disabilities and challenging behaviour were randomised to either the intervention (Stepping Stones Triple P) and treatment as usual or treatment as usual alone. The primary outcome was the parent-rated Child Behaviour Checklist at 52 weeks after randomisation. A health economic evaluation was also completed. We found no significant difference between arms on the primary outcome (mean difference -4.23; 95% CI: -9.99 to 1.53; p = 0.147). However, a subgroup analysis suggests the intervention was effective for participants randomised before the COVID-19 pandemic (mean difference -7.12; 95% CI: -13.44 to -0.81; p = 0.046). Furthermore, a complier average causal effects analysis (mean difference -11.53; 95% CI: -26.97 to 3.91; p = 0.143) suggests the intervention requires participants to receive a sufficient intervention dose. The intervention generated statistically significant cost savings (-£1,057.88; 95% CI -£3,218.6 to -£46.67) but the mean point estimate in Quality Adjusted Life Years was similar in both groups. This study did not find an effect of the intervention on reducing challenging behaviour, but this may have been influenced by problems with engagement. The intervention could be considered by services as an early intervention if families are supported to attend, especially given its low cost.

Apolipoprotein E Genetic Variant and Blood Lipid Responses to Plant Sterols: A Systematic Review and Pooled Analysis of Clinical Trials.

Plant sterols/stanols are effective cholesterol-lowering agents. However, it is unclear whether the apolipoprotein E (ApoE) genetic variants influence it. We investigated whether ApoE genetic variants modulate the responses of blood lipids to dietary intervention plant sterols/stanols in adults and if the intervention dose and duration, as well as the age and status of participants, influence this effect. Randomized clinical trials were identified by searching databases in the Cochrane Library. Random-effect models were used to estimate the pooled effect size of each outcome of interest total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. Meta-regression and subgroup analysis were used to investigate the effects of potential modifiers on the outcomes of interest. Eleven articles were selected from 3,248 retrieved abstracts. Plant sterol/stanol intervention was associated with a more significant reduction in LDL levels in the E3 group [-0.251 mmol/L; 95% confidence interval (95% CI), -0.488 to -0.015] compared with both the E4 and E2 groups. In E4 carriers, the plant sterol/stanol intervention dose and duration resulted in a larger decrease in LDL levels (-0.088027 mmol/L; 95% CI, -0.154690 to -0.021364). In conclusion, ApoE genetic variants affected the response of blood LDL levels to supplementation with plant sterols/stanols, as individuals with E3 variant showed significantly decreased LDL levels compared with the other genotypes. However, future studies recruiting participants according to their ApoE genetic variants are needed to confirm our conclusion.

Potential Therapeutic Effects of Tali Bamboo Leaf Tea (Gigantochloa apus) on Lipid Profile of Rats With Metabolic Syndrome

This study aimed to determine the potential of Tali bamboo leaf tea (Gigantochloa apus) on the lipid profile of metabolic syndrome rats. This study is an laboratory-based experimental study using 30 male Wistar rats with metabolic syndrom aged 8 weeks and weighed 150–250 g, that were divided into 5 groups namely negative control (K-), positive control (K+), and three intervention groups with intervention doses of bamboo leaf tea at 300, 600, and 900 mg/200 g BW for 28 days. The results showed that there were significant differences (p&lt;0.05) in High- Density Lipoprotein Cholesterol (HDL-C) and Low-Density Lipoprotein Cholesterol (LDL-C) levels before and after intervention. Tali bamboo leaf tea has the potential to improve the lipid profile of rats with metabolic syndrome (p&lt;0.001).

FACTORS ASSOCIATED WITH THE USE OF A PERSONALIZED MUSIC INTERVENTION FOR NURSING HOME RESIDENTS WITH DEMENTIA

Abstract Music offers a promising non-pharmacological alternative for managing behavioral dysregulations in people with Alzheimer’s disease and other dementias (ADRD). Using data from an embedded, pragmatic trial (ePCT) of a personalized music intervention for nursing home (NH) residents with ADRD, we examined resident and NH characteristics associated with exposure to the intervention and dose of music received. Participants were enrolled from 54 NHs (27 treatment, 27 control) between June 2019 and February 2020. The intervention was resident-preferred music delivered at early signs of agitation. Intervention dose was calculated by multiplying song duration and number of plays, averaged over days exposed. Facility and resident-level characteristics were identified using the Minimum Data Set and the Certification and Survey Provider Enhanced Reports. A mixed-effects hurdle model was used. 483 residents participated (67.7% female, mean age 79.8±12.2 years). Female residents (p=0.04) taking antipsychotic medications (p=0.06) were more likely to receive the intervention, as were residents from NHs with greater nursing involvement (p=0.02). Residents with greater health instability received a greater dose (p=0.04). In this ePCT of a personalized music intervention, NHs with more nursing engagement had greater use of the intervention and appropriately chose residents with antipsychotic use to participate. After adjusting for initial selection, staff used the intervention more frequently with residents who had a higher likelihood of death in the next six months, potentially indicating the beneficial use for comfort at the end of life. Our findings offer insights into future tailoring of personalized music interventions to increase the likelihood of successful implementation.

Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

In a pivotal phase 3 trial of cytomegalovirus prophylaxis with letermovir for up to 100 days after allogeneic haematopoietic stem-cell transplantation (HSCT), 12% of participants developed clinically significant cytomegalovirus infection after letermovir was discontinued. We aimed to evaluate the efficacy and safety of extending the duration of letermovir prophylaxis for clinically significant cytomegalovirus infection from 100 days to 200 days following HSCT. We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 32 sites in six countries (France, Germany, Italy, Japan, the UK, and the USA). Cytomegalovirus‑seropositive HSCT recipients (aged ≥18 years) who had received letermovir prophylaxis for up to 100 days following HSCT and who remained at high risk of late clinically significant cytomegalovirus infection (with no previous history of clinically significant cytomegalovirus infection, defined as initiation of pre-emptive therapy for documented cytomegalovirus viraemia, onset of cytomegalovirus end-organ disease, or both) were eligible. Participants were randomly assigned (2:1) to receive either an additional 100 days (ie, a total of 200 days; letermovir group) of oral or intravenous letermovir 480 mg once daily, adjusted to 240 mg once daily for participants on cyclosporin A, or 100 days of a placebo comparator for letermovir (ie, a total of 100 days of letermovir; placebo group), following HSCT. Randomisation was done using a central interactive response technology system, stratified by study centre and haploidentical donor (yes or no). Participants, investigators, and sponsor personnel were masked to the treatment allocation. The primary efficacy endpoint was the proportion of participants from randomisation to week 28 (200 days after HSCT) with clinically significant cytomegalovirus infection, analysed using the full analysis set population (ie, those who received at least one dose of study intervention). Safety was analysed in all participants as treated (ie, those who received at least one dose according to the study intervention they were assigned to). This study is registered with ClinicalTrials.gov, NCT03930615, and is complete. Between June 21, 2019, and March 16, 2022, 255 patients were screened for eligibility and 220 (86%) were randomly assigned (145 [66%] in the letermovir group and 75 [34%] in the placebo group). Between randomisation and week 28, four (3%) of 144 participants in the letermovir group and 14 (19%) of 74 in the placebo group developed clinically significant cytomegalovirus infection (treatment difference -16·1% [95% CI -25·8 to -6·5]; p=0·0005). The most common adverse events among participants in the letermovir group versus the placebo group were graft-versus-host disease (43 [30%] vs 23 [31%]), diarrhoea (17 [12%] vs nine [12%]), nausea (16 [11%] vs 13 [18%]), pyrexia (13 [9%] vs nine [12%]), and decreased appetite (six [4%] vs nine [12%]). The most frequently reported serious adverse events were recurrent acute myeloid leukaemia (six [4%] vs none) and pneumonia (three [2%] vs two [3%]). No deaths were considered to be drug-related by the investigator. Extending the duration of letermovir prophylaxis to 200 days following HSCT is efficacious and safe in reducing the incidence of late clinically significant cytomegalovirus infection in patients at risk. Merck Sharp & Dohme LLC.