Analysis Of Treatment Effects Research Articles

Effects of electroacupuncture on cognitive symptoms in major depressive disorder: a pilot study and randomized controlled trial

Objectives To investigate the impact of electroacupuncture on cognitive function, quality of life (QoL), and depression severity in patients with major depressive disorder (MDD). Methods This double-blinded randomized controlled trial included 60 participants aged 18-55 with cognitive symptoms related to MDD at Thammasat University Hospital. Participants were divided into two groups: the electroacupuncture group combined with standard antidepressant treatment (EG; n=30) and the control group receiving standard care with placebo acupuncture (CG; n=30). The study assessed 1) executive functions using the Trail making test- B and Stroop Color and Word Test, 2) delayed recall, and 3) subjective cognitive complaint and Quality of life (QoL) using WHODAS 2.0. Depressive symptoms were measured using the Thai version of the Patient Health Questionnaire (PHQ-9). Baseline and post-intervention assessments were conducted over 10 weeks. Mann-Whitney U test analyzed treatment effects by comparing median differences between groups. Results Both groups exhibited similar demographics and cognitive traits. Cognitive improvement was observed in both groups at the endpoint. Intention-to-treat analysis revealed significantly higher median scores for subjective cognitive complaints in the EG compared to the CG (EG: Median = 5.5, CG: Median = 0.0, p=0.049). No serious side effects were identified from either electroacupuncture or placebo acupuncture. Conclusions Electroacupuncture improved subjective complaints in MDD patients with cognitive symptoms, but did not show effects on specific cognitive functions, QoL, or depressive symptoms. This study provides initial evidence supporting the potential of electroacupuncture in MDD patients with cognitive symptoms, suggesting opportunities for further research. Trial registration NCT06239740, February 2, 2024, ClinicalTrials.gov.

The Effect of an Obesity Prevention Intervention Among Specific Subpopulations: A Heterogeneity of Treatment Effect Analysis of the Greenlight Trial.

Background: Understanding how different populations respond to a childhood obesity intervention could help optimize personalized treatment strategies, especially with the goal to reduce disparities in obesity. Methods: We conducted a secondary analysis of the Greenlight Cluster Randomized Controlled Trial, a health communication focused pediatric obesity prevention trial, to evaluate for heterogeneity of treatment effect (HTE) by child biological sex, caregiver BMI, caregiver reported race and ethnicity, primary language, and health literacy. To examine HTE on BMI z-score from 2 to 24 months of age, we fit linear mixed effects models. Results: We analyzed 802 caregiver-child pairs, of which 52% of children were female, 58% of households reported annual family income of <$20,000, and 83% did not have a college degree. We observed evidence to suggest HTE by primary language (p = 0.047 for Spanish vs. English) and the combination of primary language and health literacy (p = 0.01). There was insufficient evidence to suggest that the Greenlight intervention effect differed by biological sex, caregiver BMI, or by race/ethnicity. Conclusions: This HTE analysis found that the Greenlight obesity prevention intervention had a more beneficial effect on child BMI z-score over 2 years for children of caregivers with limited health literacy and for caregivers for whom Spanish was the primary language.

On the side effects of fiscal policy: Fiscal rules and income inequality

Contributing to an important literature on the side effects of fiscal policy, this paper employs a treatment effect analysis to show that fiscal rules (FR) have significant side effects on income inequality (IQ). Economically meaningful, this favorable causal direct effect is robust to many alternative specifications. Nevertheless, not all FR are alike: balanced budget and debt rules decrease IQ, contrary to expenditure rules that increase it. Finally, the effect of FR on IQ is found to be subject to heterogeneity related to various factors. Given the current upward global IQ trends, our results provide insightful evidence for governments of countries aiming at reducing IQ.

Analysis of sewage treatment process and effect Take Maidao sewage plant in Qingdao as an example

The purpose of this paper is to analyze the current situation of urban sewage treatment, understand the process of sewage treatment, conduct in-depth analysis of it combined with actual cases, and put forward effective suggestions for improvement. Nowadays, with the development of science and technology, many cities have built advanced sewage plants, as an example as Qingdao, which is a serious water shortage city in Shandong Province of China. More specifically, a field interview and a field trip in Mai Dao sewage plant provide the actual treatment process and real data of the plant. It provides with a comprehensive process and actual removal rate of the plant, so we can have a deeper understanding of the current status of urban sewage treatment processes. Additionally, an analysis of the effect of every devices in the process supports the effectiveness of the plant. Furthermore, this paper gives information about current situations of reuse water process and offers some suggestions to the current treatment process and the use of outflow water.

Dynamic fluctuations of salivary CGRP levels during migraine attacks: association with clinical variables and phenotypic characterization

BackgroundMigraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables.MethodsA prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2 h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype.ResultsA total of 44 migraine patients were included (90.9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. [SE]: 19.4 [5.8], p = 0.001) and quadratic terms of time (-19.1 [6.0], p = 0.002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18.5 [6.2], p = 0.005; quadratic-term: 19.2 [6.8], p = 0.005) was also found. Molecular phenotyping revealed that 72.7% (32/44) of patients presented only CGRP-dependent attacks, while 27.3% (12/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (p < 0.05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks.ConclusionsOur study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches.

318 Discovering Subgroups with Supervised Machine Learning Models for Heterogeneity of Treatment Effect Analysis

OBJECTIVES/GOALS: The goal of the study is to provide insights into the use of machine learning methods as a means to predict heterogeneity of treatment effect (HTE) in participants of randomized clinical trials. METHODS/STUDY POPULATION: Using data from 2,441 participants enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial of daily low-dose aspirin vs placebo in the United States, we developed multivariable risk prediction models for the composite outcome of dementia, disability, or death. We used two machine learning techniques, decision trees and random forests, to develop novel non-parametric outcomes classifiers and generate risk-based subgroups. The comparator method was an extant semi-parametric proportional hazards predictive risk model. We then assessed HTE by examining the 5-year absolute risk reduction (ARR) of aspirin vs placebo in each risk subgroup. RESULTS/ANTICIPATED RESULTS: In the random forest classifier, the ARR at 5 years in the highest risk quintile was 13.7% (95% CI 3.1% to 24.4%). For the semi-parametric proportional hazards model, the ARR in the highest risk quintile was 15.1% (95% CI 4.0% to 26.3%). These results were comparable and provide evidence of the viability of internally developed parsimonious non-parametric machine learning models for HTE analysis. The decision tree model results (5-year ARR = 17.0%, 95% CI= -5.4% to 39.4% in the highest risk subgroup) exhibited more uncertainty in the results. DISCUSSION/SIGNIFICANCE: None of the models detected significant HTE on the relative scale; there was substantial HTE on the absolute scale in three of the models. Treatment benefit on the absolute scale may be regarded as bearing greater clinical importance and may be present even in the absence of benefit on the relative scale.

패널 고정효과모형을 활용한 사회맞춤형 산학협력 선도대학(LINC+) 사업의 효과성 분석

This study used a panel fixed-effects model to analyze the effectiveness of the LINC+ project, focusing on key industry-academia-related education-related performance indicators and industry-academia cooperation outcome indicators. Through this, the purpose is to derive policy implications for the effective promotion of local government-centered industry-academia-research cooperation projects after the RISE transition. The panel fixed effects model analysis to analyze the effectiveness of the LINC+ project was analyzed by analyzing the treatment effect according to participation in the LINC+ project and the treatment intensity effect according to the size of the project cost, and was further analyzed by controlling the annual trend line and university characteristics. . In this model, the treatment effect analysis model is a model that verifies the performance between participating and non-participating universities by inserting a dummy variable for project participation, and the treatment intensity effect analysis model is a model that takes the logarithm of the support amount for each university and inputs it to participate in the project. This is a model that confirms the effectiveness of projects depending on the size of inter-university support funds. As a result of analyzing the effectiveness of the project between participating and non-participating universities through a panel fixed effects model, the performance indicators that have a static effect on project participation and project costs are the ratio of students completing capstone design and technology transfer per full-time faculty member. It appeared as an import fee. On the other hand, performance indicators that had a negative effect on project participation and project expenses were domestic research performance, employment rate, and proportion of students completing 4 weeks of field training. Based on the above analysis results, future RISE plans to continuously improve and advance the performance of industry-academia-research cooperation are as follows. First, there is a need to encourage problem-solving, industry-academia-linked curriculum such as Capstone Design to be actively reflected in the RISE project in the future. Second, each local government needs to prepare support measures to increase technology transfer fees, which is a representative result of value creation through industry-academia cooperation under RISE. Third, institutional support should be strengthened so that local governments, local companies, and local universities can discover various field training institutions through close collaboration and receive substantial field training for more than 12 weeks. Lastly, for a more rigorous analysis of the employment rate of the LINC+ project, it is necessary to analyze the effectiveness of the project only for departments participating in the LINC+ project.

Methodological biases in observational hospital studies of COVID-19 treatment effectiveness: pitfalls and potential.

This study aims to discuss and assess the impact of three prevalent methodological biases: competing risks, immortal-time bias, and confounding bias in real-world observational studies evaluating treatment effectiveness. We use a demonstrative observational data example of COVID-19 patients to assess the impact of these biases and propose potential solutions. We describe competing risks, immortal-time bias, and time-fixed confounding bias by evaluating treatment effectiveness in hospitalized patients with COVID-19. For our demonstrative analysis, we use observational data from the registry of patients with COVID-19 who were admitted to the Bellvitge University Hospital in Spain from March 2020 to February 2021 and met our predefined inclusion criteria. We compare estimates of a single-dose, time-dependent treatment with the standard of care. We analyze the treatment effectiveness using common statistical approaches, either by ignoring or only partially accounting for the methodological biases. To address these challenges, we emulate a target trial through the clone-censor-weight approach. Overlooking competing risk bias and employing the naïve Kaplan-Meier estimator led to increased in-hospital death probabilities in patients with COVID-19. Specifically, in the treatment effectiveness analysis, the Kaplan-Meier estimator resulted in an in-hospital mortality of 45.6% for treated patients and 59.0% for untreated patients. In contrast, employing an emulated trial framework with the weighted Aalen-Johansen estimator, we observed that in-hospital death probabilities were reduced to 27.9% in the "X"-treated arm and 40.1% in the non-"X"-treated arm. Immortal-time bias led to an underestimated hazard ratio of treatment. Overlooking competing risks, immortal-time bias, and confounding bias leads to shifted estimates of treatment effects. Applying the naïve Kaplan-Meier method resulted in the most biased results and overestimated probabilities for the primary outcome in analyses of hospital data from COVID-19 patients. This overestimation could mislead clinical decision-making. Both immortal-time bias and confounding bias must be addressed in assessments of treatment effectiveness. The trial emulation framework offers a potential solution to address all three methodological biases.

Low thyroxine serves as an upstream regulator of ecophysiological adaptations in Ansell's mole-rats.

About 10% of all rodent species have evolved a subterranean way of life, although life in subterranean burrows is associated with harsh environmental conditions that would be lethal to most animals living above ground. Two key adaptations for survival in subterranean habitats are low resting metabolic rate (RMR) and core body temperature (Tb). However, the upstream regulation of these traits was unknown thus far. Previously, we have reported exceptionally low concentrations of the thyroid hormone (TH) thyroxine (T4), and peculiarities in TH regulating mechanisms in two African mole-rat species, the naked mole-rat and the Ansell's mole-rat. In the present study, we treated Ansell's mole-rats with T4 for four weeks and analyzed treatment effects on the tissue and whole organism level with focus on metabolism and thermoregulation. We found RMR to be upregulated by T4 treatment but not to the extent that was expected based on serum T4 concentrations. Our data point towards an extraordinary capability of Ansell's mole-rats to effectively downregulate TH signaling at tissue level despite very high serum TH concentrations, which most likely explains the observed effects on RMR. On the other hand, body weight was decreased in T4-treated animals and Tb was upregulated by T4 treatment. Moreover, we found indications of the hypothalamus-pituitary-adrenal axis potentially influencing the treatment effects. Taken together, we provide the first experimental evidence that the low serum T4 concentrations of Ansell's mole-rats serve as an upstream regulator of low RMR and Tb. Thus, our study contributes to a better understanding of the ecophysiological evolution of the subterranean lifestyle in African mole-rats.

Hierarchical endpoints in critical care: A post-hoc exploratory analysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury and the intensity of continuous renal-replacement therapy in critically ill patients trials

PurposeTo perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR). Material and methodsAll patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy – RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis. ResultsThe WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96–1.13; p = 0.33) and 1.02 (95% CI; 0.90–1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79–0.99; p = 0.03) and 1.02 (95% CI; 0.87–1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial. ConclusionWR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation.Trial Registry: ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL).

Therapeutic Effect and Adverse Event Rate of Different Treatment Methods in Patients with Multiple Myeloma and Renal Insufficiency

Introduction: This study involves the collation and analysis of clinical characteristics and laboratory findings in patients with multiple myeloma (MM) combined with renal insufficiency. The objective was to assess the impact of various treatment methods on patient outcomes and the incidence of adverse events in individuals with MM and renal insufficiency. Methods: We analyzed the correlation between clinical characteristics, gene loci, fluorescence in situ hybridization, treatment methods, and prognosis in patients with MM and renal insufficiency. The differences in hematological and therapeutic efficacy indexes between two groups subjected to different treatments were evaluated. The assessment of treatment effectiveness was based on the total effective rate, calculated as the sum of stringent CR rate, complete remission rate, very good partial remission rate, and partial remission rate. Results: (1) The renal insufficiency group exhibited higher percentages of bone marrow abnormal plasma cells, lactate dehydrogenase (LDH), blood calcium, white blood cell count, percentage of neutrophils, and blood β2-microglobulin (β2-MG) levels compared to the normal renal function group. Conversely, hemoglobin levels and lymphocyte percentage were lower in the renal insufficiency group. Binary logistic regression analysis identified hemoglobin, blood calcium values, blood β2-MG, and LDH as independent risk factors for the development of renal insufficiency in patients with MM (p < 0.05). (2) Based on the Durie-Salmon staging criteria, the proportion of Stage III patients was the highest (up to 81.8%), indicating that patients with MM usually suffer from insidious disease, often with high tumor load and late-disease stage at the time of consultation. International Staging System (ISS) and Revised ISS staging also revealed a higher proportion of Stage III patients in the renal insufficiency group (p < 0.05), indicating a worse long-term prognosis in patients with MM and renal insufficiency. (3) Before treatment, there was no significant difference between the two groups in the analysis of various indices. Complications such as sepsis, herpes zoster, peripheral neuropathy, thrombosis, secondary pulmonary infection, and cardiac complications were significantly lower in the BCD group (Bortezomib + Cyclophosphamide + Dexamethasone) compared to the BD group (Bortezomib + Dexamethasone) (χ² = 6.333, p < 0.05), suggesting fewer complications with the BCD regimen. (4) The clinical treatment effects analysis indicated that the BCD group demonstrated a more significant impact than the BD group in the treatment of MM. Conclusion: The application of the BCD regimen in the treatment of MM has shown significant efficiency, effectively alleviating clinical symptoms with fewer adverse reactions and high safety.

From Unemployed to Self-Employed: Analysis of Treatment Effects of a Dutch Self-Employment Programme

This paper evaluates the effectiveness of a programme that aims to activate welfare recipients to become self-employed. We use unique administrative data which contain applicants for a self-employment programme between 2007 and 2010. We examine the long-term effects of the programme on people’s welfare recipience, employment and income until 8 years after they applied to the programme. The estimations show positive long-term effects of being accepted into the programme. It seems that even applying to the programme and subsequently being rejected also had positive employment effects. This was probably due to the training and guidance the applicants received while writing a business plan, which was a prerequisite to participating in the programme. Moreover, a cost–benefit analysis showed that the programme is cost-effective.

Impact of dexmedetomidine use on pediatric PACU length of stay and practice patterns: A single center study

BackgroundDexmedetomidine has been increasingly incorporated in pediatric anesthesia owing to its opioid sparing analgesic effect. In theory, dexmedetomidine may lower the use of intraoperative and postoperative opioids but increase post anesthesia care unit (PACU) patient recovery time. In 2020, the Anesthesia Department of Albany Medical Center implemented an opioid reducing initiative with dexmedetomidine incorporation as a major strategy. As such, we have carried out this retrospective study to examine the effect of dexmedetomidine on pediatric PACU length of stay (LOS) across a blend of invasive surgical procedures requiring general anesthesia. MethodsThe present study is a single-institution, retrospective chart review of children undergoing invasive procedures requiring general anesthesia at an academic center during 2021 and 2022. Convenience sampling of the first 200 patients from each of those years was analyzed (n=400). Here, we compared PACU LOS between patients who did or did not receive dexmedetomidine using the propensity-score matching treatment effects analysis. We also examined changes in perioperative medication patterns between patients who did versus did not receive dexmedetomidine. Results344 patients over the study period met inclusion criteria. The matched cohort consisted of 118 patients without dexmedetomidine administration and 122 patients with dexmedetomidine administration. The average treatment effect for administration of dexmedetomidine was an increase in PACU LOS of 19.4 min (p < 0.001). Dosages and proportion of patients receiving intraoperative or postoperative opioids did not significantly change during the study period. ConclusionsIn our center, dexmedetomidine use in pediatric procedures with general anesthesia was associated with prolonged recovery times, without a corresponding reduction in opioid use. Further investigations are therefore warranted to understand the role of dexmedetomidine as an anesthetic adjunct and in multimodal pain management.

The medium-term impact of a micronutrient powder intervention on anemia among young children in Rural China

BackgroundPoor development of young children is a common issue in developing countries and it is well established that iron deficiency anemia is one of the risk factors. Research has shown that iron deficiency is a common micronutrient deficiency among children in rural China and can result in anemia. A previous paper using data from the same trial as those used in the current study, but conducted when sample children were younger, found that after 6 months of providing caregivers of children 6–11 months of age free access to iron-rich micronutrient powder (MNP) increased the hemoglobin concentrations (Hb) of their children. However, no effects were found 12 and 18 months after the intervention. The current study followed up the children four years after the start of the original intervention (when the children were 4–5 years old) and aims to assess the medium-term impacts of the MNP program on the nutritional status of the sample pre-school-aged children, including their levels of Hb, the prevalence of anemia, and the dietary diversity of the diets of the children.MethodsAt baseline, this study sampled 1,802 children aged 6–11 months in rural Western China. The intervention lasted 18 months. In this medium-term follow-up study that successfully followed 81% (n = 1,464) of children (aged 49–65 months) from the original study population 4 years after the start of the intervention, we used both intention-to-treat (ITT) effect and average treatment on the treated effect (ATT) analyses to assess the medium-term impacts of the MNP distribution program on the nutritional status of sample children.ResultsThe ITT analysis shows that the MNP intervention decreased the prevalence of anemia of young children in the medium run by 8% (4 percentage points, p < 0.1). The ATT analysis shows that consuming 100 (out of 540) MNP sachets during the initial intervention led to a decrease in anemia of 4% (2 percentage points, p < 0.1). Among children with moderate anemia at baseline (Hb < 100 g/L), the intervention reduced the probability of anemia by 45% (9 percentage points, p < 0.1), and, for those families that complied by consuming 100 (out of 540) sachets, a 25% (5 percentage points, p < 0.05) reduction in the anemia rate was found. The MNP intervention also led to a persistent increase in dietary diversity among children that were moderately anemic at baseline. The results from the quantile treatment effect analysis demonstrated that children with lower Hb levels at baseline benefited relatively more from the MNP intervention.ConclusionsThe findings of the current study reveal that the MNP intervention has medium-term effects on the nutritional status of children in rural China. The impacts of the MNP program were relatively higher for children that initially had more severe anemia levels. Hence, the implications of this study are that programs that aim to increase caregiver knowledge of nutrition and improve their feeding practices should be encouraged across rural China. Families, policymakers, and China’s society overall need to continue to pay more attention to problems of childhood anemia in rural areas. This is particularly crucial for families with moderately anemic children at an early age as it can significantly contribute to improving the anemia status of children across rural areas of China.Trial registrationISRCTN44149146 (15/04/2013).

Effects of different intervention methods on psychological anxiety, stress, and fatigue among healthcare workers during COVID-19 pandemic: a systematic review and meta-analysis.

This study aimed to explore the treatment effects of various intervention methods on the stress, anxiety, and fatigue of medical workers during the 2019 Coronavirus Disease (COVID-19) pandemic. We conducted computer searches in both Chinese and English databases including China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wang Fang), VIP Chinese Journal Service Platform (VIP), Web of Science, Embase, PubMed, Cochrane Library, Scopus, and ScienceDirect to include prospective randomized controlled studies (Prospective RCT) published before September 30, 2023, regarding different treatment methods for stress, anxiety, and fatigue among healthcare workers during COVID-19. Data on anxiety, stress, and fatigue of research participants were extracted from the included studies, followed by statistical analysis of treatment effects using R software with the meta package. A total of 9 articles were eventually included, involving a total of 1,466 participants, including 686 in the control group and 780 in the study group. Intervention measures included mindfulness-based therapy in 4 studies and other intervention methods in 5. The anxiety status of the health workers was assessed using the Generalized Anxiety Disorder-7 (GAD-7), and the meta-analysis revealed a pooled mean difference (MD) of -0.53 (95% CI: -1.42, 0.37). Stress status was evaluated by Perceived Stress Scale 4 (PSS-4), and the meta-analysis results showed a post-treatment MD of 0.13 (95% CI: -0.39, 0.65), with a pre- and post-treatment difference MD of -0.44 (95% CI: -2.65, 1.76). Maslach Burnout Inventory (MBI) was employed for the evaluation of fatigue. The meta-analysis results showed an MD of -6.13 (95% CI: -16.68, 4.43) for the MBI Emotional index, an MD of 5.04 (95% CI: -3.25, 13.33) for the Personal Accomplishment index, and an MD of -1.68 (95% CI: -6.50, 3.13) for the Depersonalization index. Maintaining the mental health of frontline health workers is crucial during the COVID-19 pandemic, and mindfulness-based therapy is the most extensively employed psychological intervention method. However, its effectiveness requires further research confirmation.

Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Confidence distributions for treatment effects in clinical trials: Posteriors without priors.

An attractive feature of using a Bayesian analysis for a clinical trial is that knowledge and uncertainty about the treatment effect is summarized in a posterior probability distribution. Researchers often find probability statements about treatment effects highly intuitive and the fact that this is not accommodated in frequentist inference is a disadvantage. At the same time, the requirement to specify a prior distribution in order to obtain a posterior distribution is sometimes an artificial process that may introduce subjectivity or complexity into the analysis. This paper considers a compromise involving confidence distributions, which are probability distributions that summarize uncertainty about the treatment effect without the need for a prior distribution and in a way that is fully compatible with frequentist inference. The concept of a confidence distribution provides a posterior-like probability distribution that is distinct from, but exists in tandem with, the relative frequency interpretation of probability used in frequentist inference. Although they have been discussed for decades, confidence distributions are not well known among clinical trial statisticians and the goal of this paper is to discuss their use in analyzing treatment effects from randomized trials. As well as providing an introduction to confidence distributions, some illustrative examples relevant to clinical trials are presented, along with various case studies based on real clinical trials. It is recommended that trial statisticians consider presenting confidence distributions for treatment effects when reporting analyses of clinical trials.

Heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy: post hoc analysis of the CEREHETIS trial.

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair. Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk. Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method. Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%-56.7%; H2, 1.56-2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001) and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001). Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001) with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found. Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.

Luffa cylindrica (Sponge Gourd) Fibers in Treatment of Greywater: an Aerobic Fixed-Film Reactor Approach.

The need for potable water consumption in urban and suburban regions can be decreased by greywater treatment and its reuse. Utilizing natural fibers may provide sustainable solutions in addressing challenges related to water resource management. In this study, a fixed-film reactor was designed with Luffa cylindrica (an annually occurring fruit) as a bio-carrier. The lab-scale reactors were configured with and without Luffa cylindrica and were run for 90days in fed-batch mode. Scanning electron microscopy (SEM) was performed to validate biofilm production over time. Monitoring COD, nitrogen, and total phosphate removal allowed for analysis of treatment effectiveness. Results demonstrated the treatment efficiency for the experimental reactor was 70.96%, 97.02%, 92.57%, and 81.20% for COD, nitrogen, phosphate, and anionic surfactant (AS), respectively. 16s rRNA gene sequencing of bio-carrier and control greywater samples was carried out. Many bacteria known to break down anionic surfactants were observed, and microbial succession was witnessed in the control reactor vs. the experimental reactor samples. The three most prevalent genera in the experimental samples were Chlorobium, Chlorobaculum, and Terrimonas. However, it is crucial to underscore that additional research is essential to solidify our understanding in this domain, with this study laying the fundamental groundwork.

Cerebrolysin as an early add-on to reperfusion therapy: heterogeneous treatment effect analysis in ischemic stroke patients with varying risk of hemorrhagic transformation

The study goal was the assessment of heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy in stroke patients with varying risk of hemorrhagic transformation (HT). It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n=238) were stratified by HT risk with the HTI score. The study outcomes were symptomatic and any HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable outcome was defined as an mRS score of ≤2. Heterogeneous treatment effect analysis was performed using techniques of meta-analysis and the matching-smoothing method. Heterogeneity of Cerebrolysin treatment effects was moderate (I2=36.98-69.3%, H2=1.59-3.26) and mild (I2=18.33-32.39%, H2=1.22-1.48) for symptomatic and any HT, respectively. A positive impact of the Cerebrolysin treatment on HT and functional outcome was observed in patients with moderate (HTI=1) and high (HTI≥2) HT risk. However, the effect was neutral in those with low risk (HTI=0). In high HT risk patients, there was a steady decline in the rate of symptomatic (HTI=0 vs. HTI≥2: by 3.8%, p=0.120 vs. 14.3%, p<0.001) and any HT (HTI=0 vs. HTI≥2: by 0.6%, p=0.864 vs. 19.5%, p<0.001). Likewise, Cerebrolysin treatment resulted in an overall decrease in the mRS scores (HTI=0 vs. HTI≥2: by 2.1%, p=0.893 vs. 63%, p<0.001) with a reciprocal increase of the fraction with favorable outcome (HTI=0 vs. HTI≥2: by 2% p=0.634 vs. 19.2%, p<0.001). Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The Cerebrolysin positive impact was significant in those whose estimated on-admission HT risk was either moderate or high.