Comparison Of Treatment Groups Research Articles

A Unified Framework for Covariate Adjustment Under Stratified Randomisation

ABSTRACTRandomisation, as a key technique in clinical trials, can eliminate sources of bias and produce comparable treatment groups. In randomised experiments, the treatment effect is a parameter of general interest. Researchers have explored the validity of using linear models to estimate the treatment effect and perform covariate adjustment and thus improve the estimation efficiency. However, the relationship between covariates and outcomes is not necessarily linear, and is often intricate. Advances in statistical theory and related computer technology allow us to use nonparametric and machine learning methods to better estimate the relationship between covariates and outcomes and thus obtain further efficiency gains. However, theoretical studies on how to draw valid inferences when using nonparametric and machine learning methods under stratified randomisation are yet to be conducted. In this paper, we discuss a unified framework for covariate adjustment and corresponding statistical inference under stratified randomisation and present a detailed proof of the validity of using local linear kernel‐weighted least squares regression for covariate adjustment in treatment effect estimators as a special case. In the case of high‐dimensional data, we additionally propose an algorithm for statistical inference using machine learning methods under stratified randomisation, which makes use of sample splitting to alleviate the requirements on the asymptotic properties of machine learning methods. Finally, we compare the performances of treatment effect estimators using different machine learning methods by considering various data generation scenarios, to guide practical research.

Reputation Burning: Analyzing the Impact of Brand Sponsorship on Social Influencers

The growth of the influencer marketing industry warrants an empirical examination of the effect of posting sponsored videos on influencers’ reputations. We collected a novel data set of user-generated YouTube videos created by prominent English-speaking influencers in the beauty and style category. We extracted a rich set of theory-driven video features and used DiNardo-Fortin-Lemieux reweighting to construct comparable treatment and control groups matched at the influencer-video level. The empirical analysis of the matched sample revealed a reputation-burning effect; that is, posting a sponsored video, compared with posting an equivalent organic video, cost the influencers 0.19% of their reputation (operationalized as the number of subscribers). The reputation-burning effect was stronger among the influencers with larger audiences. An analysis of likes, comments, and comment texts revealed a larger gap in audience response between sponsored and organic videos among the influencers with larger (versus smaller) audiences. The reputation-burning effect was mitigated when a high fit existed between the sponsored content and the influencer’s “usual” content and when the promoted brand was less well known. Our study empirically tested the assumption of several theoretical works. Moreover, it contributes to the literature on influencer marketing and celebrity endorsements and provides managerial implications for influencers, brands, and social media platforms. This paper was accepted by D. J. Wu, information systems. Funding: This research was supported by funding provided by Harvard Business School. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.00193 .

Efficacy and Safety of a Tubeless AID System Compared With Pump Therapy With CGM in the Treatment of Type 1 Diabetes in Adults With Suboptimal Glycemia: A Randomized, Parallel-Group Clinical Trial.

To examine the efficacy and safety of the tubeless Omnipod® 5 Automated Insulin Delivery (AID) System compared with pump therapy with a continuous glucose monitor (CGM) in adults with type 1 diabetes with suboptimal glycemic outcomes. In this 13-week multicenter, parallel-group, randomized controlled trial performed in the U.S. and France, adults aged 18-70 years with type 1 diabetes and HbA1c 7-11% (53-97 mmol/mol) were randomly assigned (2:1) to intervention (tubeless AID) or control (pump therapy with CGM) following a 2-week standard therapy period. The primary outcome was a treatment group comparison of time in range (TIR) (70-180 mg/dL) during the trial period. A total of 194 participants were randomized, with 132 assigned to the intervention and 62 to the control. TIR during the trial was 4.2h/day higher in the intervention compared with the control group (mean difference 17.5% [95% CI 14.0%, 21.1%]; P < 0.0001). The intervention group had a greater reduction in HbA1c from baseline compared with the control group (mean ± SD -1.24 ± 0.75% [-13.6 ± 8.2 mmol/mol] vs. -0.68 ± 0.93% [-7.4 ± 10.2 mmol/mol], respectively; P < 0.0001), accompanied by a significantly lower time <70 mg/dL (1.18 ± 0.86% vs. 1.75 ± 1.68%; P = 0.005) and >180 mg/dL (37.6 ± 11.4% vs. 54.5 ± 15.4%; P < 0.0001). All primary and secondary outcomes were met. No instances of diabetes-related ketoacidosis or severe hypoglycemia occurred in the intervention group. Use of the tubeless AID system led to improved glycemic outcomes compared with pump therapy with CGM among adults with type 1 diabetes, underscoring the clinical benefit of AID and bolstering recommendations to establish AID systems as preferred therapy for this population.

A systematic assessment of robustness in CNS safety pharmacology.

Irwin tests are key preclinical study elements for characterising drug-induced neurological side effects. This multicentre study aimed to assess the robustness of Irwin tests across multinational sites during three stages of protocol harmonisation. The projects were part of the Enhanced Quality in Preclinical Data framework, aiming to increase success rates in transition from preclinical testing to clinical application. Female and male NMRI mice were assigned to one of three groups (vehicle, MK-801 0.1and 0.3 mg kg-1). Irwin scores were assessed at baseline and multiple times following intraperitoneal injection of MK-801 using local protocols (Stage 1), shared protocols with harmonised environmental design (Stage 2) and fully harmonised Irwin scoring protocols (Stage 3). The analysis based on the four functional domains (motor, autonomic, sedation and excitation) revealed substantial data variability in Stages 1 and 2. Although there was still marked overall heterogeneity between sites in Stage 3 after complete harmonisation of the Irwin scoring scheme, heterogeneity was only moderate within functional domains. When comparing treatment groups versus vehicle, we found large effect sizes in the motor domain and subtle to moderate effects in the excitation-related and autonomic domains. The pronounced interlaboratory variability in Irwin datasets for the CNS-active compound MK-801 needs to be carefully considered when making decisions during drug development. While environmental and general study design had a minor impact, the study suggests that harmonisation of parameters and their scoring can limit variability and increase robustness.

Effects of Switching FSH Preparations on Sperm Parameters and Pregnancy: A Prospective Controlled Study

Objective: To study the effect of switching to a follicle-stimulating hormone (FSH) preparation other than that to which infertile male patients have not had an effective response. Patients and methods: Seventy-four normogonadotropinemic, non-obstructive, oligozoospermic patients who were poor responders to the administration of highly purified FSH (hpFSH) (Group 1 (n = 22) and Group 3 (n = 15)) or to recombinant human FSH (rhFSH) (Group 2 (n = 22) and Group 4 (n = 15)) were selected for this prospective study. After 3 months of washout from treatment with the first FSH preparation of choice, rhFSH was administered to patients in Groups 1 and 4 and hpFSH to those in Groups 2 and 3. Serum luteinizing hormone, FSH, total testosterone levels, conventional sperm parameters, testicular volume, and the number of pregnancies were evaluated at study entry and after the first and second treatment cycles. Results: Comparing treatment groups, the greatest improvement in sperm parameters was recorded in the groups of patients prescribed the switch in FSH preparation. Group 1 had the greatest benefit from therapy, with the highest pregnancy rate after the second treatment cycle. Indeed, eight couples achieved pregnancy (36.4%), compared to Groups 2 (n = 4; 18.2%), 3 (n = 1; 6.7%), and 4 (n = 2; 13.3%) (p = 0.04). Conclusions: The results of this study suggest that a therapeutic scheme involving the “switching” of the FSH preparation yields better results than a protocol using the same FSH preparation for six months. These findings, if confirmed by further studies, will help us better design a treatment strategy with FSH for infertile patients with oligozoospermia.

Comparative quantitative phosphoproteomic and parallel reaction monitoring analysis of soybean roots under aluminum stress identify candidate phosphoproteins involved in aluminum resistance capacity

Aluminum (Al) toxicity adversely impacts soybean (Glycine max) growth in acidic soil. Reversible protein phosphorylation plays an important role in adapting to adverse environmental conditions by regulating multiple physiological processes including signal transduction, energy coupling and metabolism adjustment in higher plant. This study aimed to reveal the Al-responsive phosphoproteins to understand their putative function and involvement in the regulation of Al resistance in soybean root. We used immobilized metal affinity chromatography to enrich the key phosphoproteins from soybean root apices at 0, 4, or 24 h Al exposure. These phosphoproteins were detected using liquid chromatography-tandem mass spectrometry measurement, verified by parallel reaction monitoring (PRM), and functionally characterized via overexpression in soybean hairy roots. A total of 638 and 686 phosphoproteins were identified as differentially enriched between the 4-h and 0-h, and the 24-h and 0-h Al treatment comparison groups, respectively. Typically, the phosphoproteins involved in biological processes including cell wall modification, and RNA and protein metabolic regulation displayed patterns of decreasing enrichment (clusters 3, 5 and 6), however, the phosphoproteins involved in the transport and metabolic processes of various substrates, and signal transduction pathways showed increased enrichment after 24 h of Al treatment. The enrichment of phosphoproteins in organelle organization bottomed after 4 h of Al treatment (cluster 1). Next, we selected 26 phosphoproteins from the phosphoproteomic profiles, assessed their enrichment status using PRM, and detected enrichment patterns similar to those observed via phosphoproteomic analysis. Among them, 15 phosphoproteins were found to reduce the accumulation of Al and callose in Al-stressed soybean root apices when their corresponding genes were individually overexpressed in soybean hairy roots. In summary, the findings of this study facilitated a comprehensive understanding of the protein phosphorylation events involved in Al resistance responses and revealed some critical phosphoproteins that enhance Al resistance in soybean roots.

Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study.

Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting. Patients with gastric adenocarcinoma and synchronous peritoneal metastases (with or without other metastases) diagnosed in the Netherlands between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Median overall survival (OS) and time-to-treatment failure were determined and multivariable Cox regression analyses were used to compare treatment groups, corrected for relevant tumor and patient characteristics. In total, 1,972 patients were included, of whom 842 (43%) were treated with palliative systemic therapy. The majority received capecitabine + oxaliplatin (CAPOX; 44%), followed by fluorouracil/leucovorin/oxaliplatin (FOLFOX; 19%), and epirubicin + capecitabine + oxaliplatin (EOX; 8%). Of the 99 (45%) patients who received second-line systemic treatment, ramucirumab + paclitaxel were administered most frequently (63%). After adjustment for sex, age, comorbidities, performance status, tumor location, Lauren classification, and the presence of metastases outside of the peritoneum, patients treated with a triplet containing docetaxel and those treated with a regimen containing trastuzumab had a significantly longer OS compared with patients treated with a doublet containing a fluoropyrimidine derivate + oxaliplatin (hazard ratio [HR], 0.69; 95% CI, 0.52-0.91, and HR, 0.68; 95% CI, 0.51-0.91, respectively). Monotherapy was associated with a shorter OS (HR, 2.08, 95% CI, 1.53-2.83). There is substantial heterogeneity in systemic treatment choices in patients with gastric cancer and peritoneal metastases in the Netherlands. In this study, patients treated with triplets containing docetaxel and with trastuzumab-containing regimens survived longer than patients who received doublet therapy. Despite this, median OS for all treatment groups remained below one year.

Frequent Error Augmentation Training in Physical Therapy Post Stroke.

The purpose of this pilot trial was to evaluate the impact of increased frequency of physical therapy sessions with error augmentation on functional mobility and disability outcomes in patients with acute stroke. We hypothesized that participants receiving frequent error augmentation physical therapy interventions (F-EA-PT) would demonstrate a higher degree of improvement on functional mobility and disability measures from admission to three post-intervention time points (treatment day 3, discharge, or 90-day follow-up). We allocated 100 individuals to receive either F-EA-PT or standard-of-care physical therapy (SOC-PT). The F-EA-PT group received physical therapy with error augmentation twice daily for 3 out of the first 5 days of hospitalization, and daily treatment sessions thereafter. Error augmentation training emphasizes impairments throughout mobility to challenge the individual, rather than facilitating normal movement patterns. The SOC-PT group received treatment once daily for 3 to 5 days per week. Assessments included National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Activity Measure for Post-Acute Care (AM-PAC) and Postural Assessment Scale for Stroke (PASS). A repeated measures mixed model approach compared treatment groups for all outcomes. The F-EA-PT group demonstrated larger magnitudes of reduction of -1.34 on NIHSS (p=0.0426) and -0.81 on mRS (p=0.0037) from admission to 90-day follow-up compared to the SOC-PT group. The F-EA-PT group demonstrated larger magnitudes of change in AM-PAC of 2.12 at treatment day 3 (p=0.0009) and 2.75 at discharge (p<0.0001) compared to SOC-PT. F-EA-PT group experienced greater improvement in PASS over the SOC-PT group with a difference in change of 4.08 at treatment day 3 (p=0.0019) and 4.45 at discharge (p=0.001). Intervening with a regimen focused on increased frequency and error augmentation from a physical therapy standpoint was safe with only one adverse event. It demonstrated significant improvements in functional outcomes post stroke above those seen with standard-of-care regimen, as evidenced by PASS and AM-PAC scores. URL: https://www.clinicaltrials.gov. Unique identifier: NCT04778475.Medical University of South Carolina IRB II Approved 04/20/2021 PRO00108635.

Discontinuation Rate of Lurasidone and Quetiapine Extended Release in Bipolar Depression.

Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317). This is a retrospective cohort study. Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively. The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.

The Effect of Coordinating the Outpatient Treatment across Medical Specialities for Patients With Multimorbidity.

Patients with multimorbidity attend multiple outpatient clinics. We assessed the effects on hospital use of scheduling several outpatient appointments to same-day visits in a multidisciplinary outpatient pathway (MOP). This study used a quasi-experimental design. Eligible patients had multimorbidity, were aged ≥18 years and attended ≥2 outpatient clinics in five different specialties. Patients were identified through forthcoming appointments from August 2018 to March 2020 and divided into intervention group (alignment of appointments) and comparison group (no alignment). We used patient questionnaires and paired analyses to study care integration and treatment burden. Using negative binomial regression, we estimated healthcare utilisation as incidence rates ratios (IRRs) at one year before and one year after baseline for both groups and compared IRR ratios (IRRRs). Intervention patients had a 19% reduction in hospital visits (IRRR: 0.81, 95% CI: 0.70-0.96) and a 17% reduction in blood samples (IRRR: 0.83, 0.73-0.96) compared to comparison patients. No effects were found for care integration, treatment burden, outpatient contacts, terminated outpatient trajectories, hospital admissions, days of admission or GP contacts. The MOP seemed to reduce the number of hospital visits and blood samples. These results should be further investigated in studies exploring the coordination of outpatient care for multimorbidity. Can an intervention of coordinating outpatient appointments to same-day visits combined with a multidisciplinary conference influence the utilisation of healthcare services and the patient-assessed integration of healthcare services and treatment burden among patients with multimorbidity?

Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials

IntroductionAnifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using...

Randomized Controlled Trials to Treat Obesity in Military Populations: A Systematic Review and Meta-Analysis

IntroductionIn recent years, overweight and obesity have reached an alarmingly high incidence and prevalence worldwide; they have also been steadily increasing in military populations. Military personnel as an occupational group are often exposed to stressful and harmful environments that represent a risk factor for disordered eating with major repercussions on both physical and mental health.ObjectivesThis study aims to explore the effectiveness of weight loss interventions and to assess the significance of current obesity treatments for military populations.MethodsThree online databases (PubMed, PsycInfo, and Web of Science) were screened to identify randomized controlled trials (RCTs) aiming to treat obesity in active-duty military personnel and veterans. Random-effects meta-analyses were conducted for body weight (BW) and body mass index (BMI) values, both longitudinally comparing treatment group from pre-to-post intervention, and cross-sectionally comparing the treatment group to controls at the end of the intervention.ResultsA total of 21 studies were included: 16 cross-sectional (BW: n=15; BMI: n=12) and 16 longitudinal (BW: n=15; BMI: n=12) were meta-analyzed, and 5 studies were narratively synthesized. A significant small overall BW and BMI reduction from baseline to post-intervention was observed (BW: g = -0.10; p = 0.015; BMI: g = -0.32; p &lt; 0.001), together with a decreased BMI ( g = -0.16; p = 0.001) and nominally lower BW ( g = -0.08; p = 0.178) in the intervention group compared to controls at post-intervention time-point. When conducting additional meta-analyses dividing by sample type, a significant decrease in both BMI (g= -0.35; p&lt; 0.001) and BW (g= -0.12; p= 0.041) from pre-to-post intervention was observed in active-duty military personnel but not for veterans.Recommendations for clinical practice have been outlined from the findings of this study and summarized in Figure 1.Image:ConclusionsDespite limitations, such as the heterogeneity across the included interventions and the follow-up duration, our findings highlight how current weight loss interventions are effective in term of BW and BMI reductions in military populations, and how a comprehensive approach with multiple therapeutic goals should be taken during the intervention.Disclosure of InterestNone Declared

Impact of Targeted Agents on Survival of Chronic Lymphocytic Leukemia Patients Fit for Fludarabine, Cyclophosphamide, and Rituximab (FCR) Relative to Age- and Sex-Matched Population.

To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7-58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was -0.4 months (95% CI: -0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: -0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: -1.6 months; 95% CI: -2.4 to -0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: -0.9 months; 95% CI: -1.7 to -0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP.

Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation – Clinical and safety results

IntroductionWe investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. Material and methodsPatients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. ResultsTwenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (−5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01).Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DiscussionOur results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

Dietary Intervention Favorably Influences Physical Functioning: The Women’s Health Initiative Randomized Dietary Modification Trial

BackgroundIn the Women’s Health Initiative Dietary Modification randomized trial, the dietary intervention reduced breast cancer mortality by 21% (P = .02) and increased physical activity as well. ObjectiveTherefore, the aim was to examine whether or not these lifestyle changes attenuated age-related physical functioning decline. DesignIn a randomized trial, the influence of 8 years of a low-fat dietary pattern intervention was examined through 20 years of cumulative follow-up. Participants and settingFrom 1993 to 1998, 48,835 postmenopausal women, ages 50 to 79 years with no prior breast cancer and negative baseline mammogram were randomized at 40 US clinical centers to dietary intervention or usual diet comparison groups (40 out of 60). The intervention significantly reduced fat intake and increased vegetable, fruit, and grain intake. Main outcome measuresIn post hoc analyses, physical functioning, assessed using the RAND 36-Item Short Form Health Survey, evaluated quality or limitations of 10 hierarchical physical activities. Longitudinal physical functioning, reported against a disability threshold (when assistance in daily activities is required) was the primary study outcome. Statistical analyses performedSemiparametric linear mixed effect models were used to contrast physical functioning trajectories by randomization groups. ResultsPhysical functioning score, assessed 495,317 times with 11.0 (median) assessments per participant, was significantly higher in the intervention vs comparison groups through 12 years of cumulative follow-up (P = .001), representing a reduction in age-related functional decline. The intervention effect subsequently attenuated and did not delay time to the disability threshold. Among women in the dietary intervention vs comparison groups, aged 50 to 59 years, who were physically inactive at entry, a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold by approximately a year was seen (P value for interaction = .007). ConclusionsIn the Women’s Health Initiative Dietary Modification randomized trial, a dietary intervention that significantly reduced breast cancer mortality also significantly reduced age-related functional decline through 12 years, which was attenuated with longer follow-up.

Investigating of augmented reality and cold vibration therapy on anxiety in children during intravenous insertion: a quasi-experimental study

Anxiety tends to escalate when children undergo intravenous insertion. The success rate of the first attempt at intravenous insertion is suboptimal, leading to increased anxiety in children and prolonged treatment. Unfortunately, current interventions are not yet optimal. This study aimed to determine the influence of augmented reality and cold vibration on children's anxiety during intravenous insertion procedure. This research used an experimental pre-post-test nonequivalent control group design. Purposive sampling was employed, taking into consideration inclusion and exclusion criteria. The instrument used demographic data and Child Anxiety Meter (CAM). The independent variables in this study are augmented reality and cold vibration. The dependent variable is anxiety. The total sample consisted of 60 respondents divided into an intervention group (n=30) and comparison group (n=30). Descriptive statistics, frequency distribution, percentages, Paired T-test, Wilcoxon, and Independent T-test were applied for data analysis. Participants in the intervention group experienced a decrease in mean higher anxiety score (2.03), compared to the comparison group (0.59). The independent t-test indicated &lt;0.001 (&lt;0.05) for a p-value. Based on these results, the application of augmented reality and cold vibration can be considered as non-pharmacological therapy to reduce anxiety. The results of this research are very useful for preparing operational plans and developing inpatient service systems, especially in providing health services to pediatric patients during intravenous insertion.

Effect of Inclusive Early Childhood Development (IECD) on Growth and Development of Children in the Rural Part of the Central India: A Cohort Study.

To compare the difference between the growth and developmental status of the children who were residing in the area where Inclusive Early Childhood Development (IECD) project was being implemented and who had received interventions through trained Anganwadi workers (Frontline workers) under Integrated Child Development Services (ICDS) scheme with the children who had not received the Inclusive ECD project interventions. It was a mixed method cohort study, nested in an ongoing project in a medical college in which Inclusive ECD was used as an intervention through International Guide for Monitoring Child Development (GMCD) which is a tool for both monitoring and assessment with the help of existing government structures and personnel such as Anganwadi workers, Anganwadi supervisors and their contact points with communities. A sample of 200 children was selected; 100 each from intervention group (IECD cohort) and comparison group (Usual care cohort) and were followed till the child became 2 y of age. IECD intervention showed statistically significant effect on weight (p = 0.04) and height (p = 0.03) of the IECD cohort. Overall developmental assessment showed that the identified developmental issues (Concerns + Delays) were approximately half in IECD cohort (9.67%+5.37%=15.04%) as compared to usual care cohort (17.20%+11.82%=29.02%). The results from binomial logistic regression performed for developmental outcomes were statistically significant (p = 0.04) suggesting that children with IECD intervention have lower odds of developing developmental issues. The study indicates that it is possible to implement IECD interventions through frontline workers, which significantlyimproves the growth and development of the children.

Evaluation of the Treatment Programme for Families with Children in Andalusia: An analysis of the impact on the children

AbstractThe Treatment Programme for Families with Children in Andalusia is fundamentally aimed at promoting the integral development of children and adolescents through the strengthening of parental competences and family preservation strategies. In the last 20 years, this programme has been applied to over 75 000 families, involving about 150 000 children and adolescents. The aim of this study was to analyse the effects of this family intervention programme on the quality of life and behaviour problems of the children. This quasi‐experimental and longitudinal study had two non‐randomized groups (intervention group and comparison group) and two evaluation measures (pre‐treatment and post‐treatment). The intervention group was constituted by 297 families (540 children) who had participated in the programme. The comparison group consisted of 95 families (138 children) at a similar risk level, although these families had not participated in the programme. The results showed a significant improvement in the quality of life of the children of the families that belonged to the intervention group, which was significantly greater than the evolution detected in the children of the families that belonged to the comparison group. The results of efficacy and efficiency of this type of practice constitute a quality criterion of evidence‐based programmes and a requirement to maintain public investment.

Effects of EPs 7630 on Illness Absence from Childcare or School due to Acute Bronchitis—A Meta-analysis

Abstract Objective In the pediatric population, acute bronchitis (AB) is a leading cause of illness absence from childcare, school, or apprenticeship. We report a meta-analysis of double-blind, randomized trials with children and adolescents with AB (aged 1–18 years), who were treated with Pelargonium extract EPs 7630 or placebo for 7 days. Methods The average number of days absent from childcare, school, or apprenticeship due to illness and the proportion of patients still unable to return to their normal activities at treatment end were assessed. Results Literature search identified two eligible trials with a total of 420 patients. Illness absence was reported for all but two patients under placebo at baseline and for 46.7% (EPs 7630) and 85.0% (placebo) of patients at day 7. Meta-analysis risk ratio for absence at day 7 was 0.55 (95% confidence interval: 0.47, 0.64) for all patients, 0.59 (0.46, 0.76) for children younger than 6 years, and 0.53 (0.44, 0.64) for participants aged 6 to 18 years, all favoring EPs 7630. Compared with placebo, average time until return to normal activities was reduced by EPs 7630 by 1.51 (1.16, 1.86) days for all subjects, by 1.50 (0.92, 20.7) days for those younger than 6 years, and by 1.54 (1.11, 1.97) days for those 6 to 18 years of age (p &lt; 0.001 favoring EPs 7630 for all treatment group comparisons shown). Conclusion For children and adolescents with AB, meta-analysis shows that EPs 7630 treatment for 7 days significantly reduces the average time of illness absence and significantly increases the proportion of patients able to return to normal activities within 1 week.

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis.

Background: Ulcerative colitis is a chronic immune-mediated inflammatory bowel disease that involves inflammation and ulcers of the colon and rectum. To date, no definite cure for this disease is available. Objective: The objective of the current study was to assess the effect of Calliandra haematocephala on inflammatory mediators and oxidative stress markers for the exploration of its anti-ulcerative colitis activity in rat models of acetic acid-induced ulcerative colitis. Methods: Methanolic and n-hexane extracts of areal parts of the plant were prepared by cold extraction method. Phytochemical analysis of both extracts was performed by qualitative analysis, quantitative methods, and high-performance liquid chromatography (HPLC). Prednisone at 2mg/kg dose and plant extracts at 250, 500, and 750mg/kg doses were given to Wistar rats for 11days, which were given acetic acid on 8th day through the trans-rectal route for the induction of ulcerative colitis. A comparison of treatment groups was done with a normal control group and a colitis control group. To evaluate the anti-ulcerative colitis activity of Calliandra haematocephala, different parameters such as colon macroscopic damage, ulcer index, oxidative stress markers, histopathological examination, and mRNA expression of pro and anti-inflammatory mediators were evaluated. mRNA expression analysis was carried out by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: The phytochemical evaluation revealed polyphenols, flavonoids, tannins, alkaloids, and sterols in both extracts of the plant. Results of the present study exhibited that both extracts attenuated the large bowel inflammation and prevented colon ulceration at all tested doses. Macroscopic damage and ulcer scoreswere significantly decreased by both extracts. Malondialdehyde (MDA) levels and nitrite/nitrate concentrations in colon tissues were returned to normal levels while superoxide dismutase (SOD) activity was significantly improved by all doses. Histopathological examination exhibited that both extracts prevented the inflammatory changes, cellular infiltration, and colon thickening. Gene expression analysis by RT-qPCR revealed the downregulation of pro-inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) whereas the anti-inflammatory cytokines including Interleukin-4 (IL-4) and Interleukin-10 (IL-10) were found to be upregulated in treated rats. Conclusion: It was concluded based on study outcomes that methanolic and n-hexane extracts of Calliandra haematocephala exhibited anti-ulcerative colitis activity through modulation of antioxidant defense mechanisms and the immune system. In this context, C. haematocephala can be considered as a potential therapeutic approach for cure of ulcerative colitis after bioassay-directed isolation of bioactive phytochemicals and clinical evaluation.