Randomized Control Trial Design Research Articles

It is Time to Address Fear of Cancer Recurrence in Family Caregivers: Feasibility and Acceptability of a Randomized Pilot Study of the Family Caregiver Version of the Fear of Recurrence Therapy (FC-FORT).

Fear of cancer recurrence (FCR) is common, persistent, and associated with lower quality of life, impaired functioning, and psychological distress in family caregivers (FC) of individuals with a cancer diagnosis. Interventions are needed to specifically target FCR in FC. This study aimed to pilot test the adapted Family Caregiver-Fear Of Recurrence Therapy (FC-FORT) to establish its feasibility, acceptability, and clinical significance. This pilot study used a mixed-method, parallel, two-group randomized control trial (FC-FORT vs. waitlist control group) design. Women FC were recruited through Canadian hospitals, community partners, and social media. FC in the intervention group completed 7 weekly sessions of virtual group therapy (FC-FORT) and an exit interview. All participants completed questionnaires at baseline, post-intervention, and 3-month follow-up. Feasibility (e.g., recruitment, allocation, fidelity), acceptability (e.g., dropout, completion, satisfaction) and clinical significance of secondary outcomes were evaluated. Descriptive statistics, mixed ANOVAs, and conventional content analyses were used. Regarding feasibility, 22 FC were recruited, 18 were randomized and therapist fidelity was 87%. As to acceptability, 67% of participants completed 5 sessions (33% dropout). Questionnaire completion rate was 92%. FC satisfaction was 80%. Analyses did not reveal any significant differences on the secondary outcomes between groups. Qualitative analyses revealed high importance, helpfulness, satisfaction, and group cohesion. Suggestions were made by FC for improvements. This is one of the first interventions to address FCR in FC. While acceptability of FC-FORT was good, important feasibility issues need to be addressed before moving forward with a larger randomized control trial. NCT, NCT05441384. Registered July 1st, 2022, https://classic. gov/ct2/show/NCT05441384.

TAD-SIE: sample size estimation for clinical randomized controlled trials using a Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator

BackgroundPhase-3 clinical trials provide the highest level of evidence on drug safety and effectiveness needed for market approval by implementing large randomized controlled trials (RCTs). However, 30–40% of these trials fail mainly because such studies have inadequate sample sizes, stemming from the inability to obtain accurate initial estimates of average treatment effect parameters.MethodsTo remove this obstacle from the drug development cycle, we present a new algorithm called Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator (TAD-SIE) that powers a parallel-group trial, a standard RCT design, by leveraging a state-of-the-art hypothesis testing strategy and a novel trend-adaptive design (TAD). Specifically, TAD-SIE uses synthetic intervention (SI) to estimate individual treatment effects and thereby simulate a cross-over design, which makes it easier for a trial to reach target power within trial constraints (e.g., sample size limits). To estimate sample sizes, TAD-SIE implements a new TAD tailored to SI given that using it violates assumptions under standard TADs. In addition, our TAD overcomes the ineffectiveness of standard TADs by allowing sample sizes to be increased across iterations without any condition while controlling significance level with futility stopping. Our TAD also introduces a hyperparameter that enables trial designers to trade off between accuracy and efficiency (sample size and number of iterations) of the solution.ResultsOn a real-world Phase-3 clinical RCT (i.e., a two-arm parallel-group superiority trial with an equal number of subjects per arm), TAD-SIE obtains operating points ranging between 63% to 84% power and 3% to 6% significance level in contrast to baseline algorithms that get at best 49% power and 6% significance level.ConclusionTAD-SIE is a superior TAD that can be used to reach typical target operating points but only for trials with rapidly measurable primary outcomes due to its sequential nature. The framework is useful to practitioners interested in leveraging the SI algorithm for their study design.

The Effect of Myofascial Release Applied to Thoracolumbar Fascia on Flexibility, Muscular Endurance, and Balancein Healthy Young Adults: A Single-Blind Randomized Controlled Trial.

Although cranial distant effects occur in self-myofascial release interventions for lower-extremity muscles and fascia, the results of caudal distant effects are still unclear. The aim of this study was to examine the distant effects of myofascial release applied to the thoracolumbar fascia together with exercise training on balance, lower-extremity flexibility, and muscular endurance in healthy young adults. Single-blinded randomized control trial design. Thirty-six healthy participants aged 18-35years were randomly divided into 3 groups: myofascial release and exercise group (group 1, n = 12), exercise group (group 2, n = 12), and control group (group 3, n = 12). Threedays a week for 4weeks, group 1 applied the thoracolumbar fascia foam roller massage together with the warm-up, muscular endurance, balance, and stretching exercise program, and group 2 applied the same exercise program except for the foam roller massage. No intervention was made in group3. Flexibility was assessed with sit and reach test, muscular endurance with the 1-minute sit to stand test, and balance with star excursion balance test before the intervention and at the end of the fourth week. Flexibility, muscular endurance, and dynamic balance values increased significantly in groups 1 and 2 after the intervention (P < .05). When the difference values (Δ) of groups 1 and 2 were compared, there was a difference in favor of group 1 for flexibility, muscular endurance, and dynamic balance (P < .05). The results of the study showed that the effect of the distant myofascial release technique added to the exercise training on flexibility, muscular endurance, and dynamic balance was greater than the exercise training alone.

Investigating the impact of microbiome-changing interventions on food decision-making: MIFOOD study protocol

BackgroundObesity is a multifactorial disease reaching pandemic proportions with increasing healthcare costs, advocating the development of better prevention and treatment strategies. Previous research indicates that the gut microbiome plays an important role in metabolic, hormonal, and neuronal cross-talk underlying eating behavior. We therefore aim to examine the effects of prebiotic and neurocognitive behavioral interventions on food decision-making and to assay the underlying mechanisms in a Randomized Controlled Trial (RCT).MethodThis study uses a parallel arm RCT design with a 26-week intervention period. We plan to enroll 90 participants (male/diverse/female) living with overweight or obesity, defined as either a Waist-to-Hip Ratio (WHR) ≥ 0.9 (male)/0.85 (diverse, female) or a Body Mass Index (BMI) ≥ 25 kg/m2. Key inclusion criteria are 18–60 years of age and exclusion criteria are type 2 diabetes, psychiatric disease, and Magnetic Resonance Imaging (MRI) contraindications. The interventions comprise either a daily supplementary intake of 30 g soluble fiber (inulin), or weekly neurocognitive behavioral group sessions, compared to placebo (equicaloric maltodextrin). At baseline and follow-up, food decision-making is assessed utilizing task-based MRI. Secondary outcome measures include structural MRI, eating habits, lifestyle factors, personality traits, and mood. Further, we obtain fecal and blood samples to investigate gut microbiome composition and related metabolites.DiscussionThis study relies on expanding research suggesting that dietary prebiotics could improve gut microbiome composition, leading to beneficial effects on gut-brain signaling and higher-order cognitive functions. In parallel, neurocognitive behavioral interventions have been proposed to improve unhealthy eating habits and metabolic status. However, causal evidence on how these “bottom-up” and “top-down” processes affect food decision-making and neuronal correlates in humans is still scarce. In addition, microbiome, and gut-brain-axis-related mediating mechanisms remain unclear. The present study proposes a comprehensive approach to assess the effects of these gut-brain-related processes influencing food decision-making in overweight and obesity.Trial registrationClinicalTrials.gov NCT05353504. Retrospectively registered on 29 April 2022.

Testing the effectiveness of a new French assisted resilience program among long-term unemployed people: a randomized control trial

ABSTRACT Long-term unemployment can affect life satisfaction, reduce well-being and increase mental health problems. Promoting psychological resilience to support the ability to cope with life challenges such as unemployment, may be a useful strategy. A specific program named AD-Ré was designed for Long-Term Unemployed (LTU) people in order to improve their mental health by fostering psychological resilience. A randomized control trial design was used. A total of 160 LTU people, recruited from the French National Employment Service, were randomly assigned to the experimental group (n = 89) or the control group (n = 71). The experimental condition consisted in following the usual counseling protocol and participating in the assisted resilience program AD-Ré while the control condition consisted in following the usual counseling protocol only. Resilience and mental-health outcomes were measured at baseline (T1) and following the last session of the program (T2). The results were analyzed using descriptive statistics, repeated measures analysis of variance (ANOVA) and t-test. ANOVA showed a significant crossed effect between time and group on resilience, well-being, and emotional dysregulation measures (p < .05) and a trend effect on perceived stress and optimism measures (p < 10). The intervention had a significant effect on resilience (d = 0.62), well-being (d = 0.37) and emotional dysregulation (d = 0.32) and a trend effect on perceived stress measures (d = 0.26). For the first time in France, an assisted resilience program significantly improved psychological resilience among LTU compared to an usual counseling protocol.

Effects of interventions aimed at improving nurses’ work engagement in the workplace: a systematic review and meta-analysis protocol

IntroductionWork engagement enhances nurses’ physical and mental health, well-being, job performance and satisfaction. This reduces turnover rates and improves patient care quality, making work engagement a crucial factor in the...

Protocol for an adaptive platform trial of intended service user-derived interventions to equitably reduce non-attendance in eye screening programmes in Botswana, India, Kenya and Nepal

IntroductionOnly 30%–50% of people referred to clinics during community-based eye screening are able to access care in Botswana, India, Kenya and Nepal. The access rate is even lower for certain...

Trauma web-based psychoeducational programme: systematic cultural adaptation and protocol for a feasibility-acceptability study

ABSTRACT Background: Trauma exposure in Indonesia is high despite the fact that there is limited accessibility to mental healthcare. Pulihkan Luka (PL) is a web-based trauma psychoeducation intervention that aims to provide a practical solution to overcome barriers to accessing mental healthcare. Objectives: This article aimed to (1) describe the cultural adaptation process of PL for Indonesian students and (2) describe the design of the pilot randomised controlled trial (RCT) that examines the feasibility and acceptability of PL. Methods: First, we describe the cultural adaptation process of PL following the 5-phase Formative Method for Adapting Psychotherapy (FMAP) approach: (1) knowledge generation, (2) information integration, (3) review and revision, (4) mini-testing, and (5) finalisation. Focus Group Discussion (FGD) was conducted to gather the views of 15 stakeholders on psychoeducation material and trauma-related mental health problems. Based on the outcomes, we decided to utilise the informal Indonesian language, incorporate practical worksheets and infographics, which include illustrations that reflect Indonesia’s cultural diversity, and provide guidance on seeking help that aligns with the mental health system in Indonesia. Second, we describe the design of a pilot RCT. Undergraduate students (N = 130) will be randomised to (1) four to seven sessions of PL + Enhanced Usual Care (PL + EUC; n = 65) or (2) Enhanced Usual Care only (EUC only; n = 65). Assessments will be conducted at baseline, post-intervention, and three and six-month follow-up. Additionally, 20 participants will be invited for an FGD to explore their experiences with the intervention. Quantitative data will be analysed using linear mixed-effect models, and qualitative data will be analysed using thematic analysis. Discussion: Cultural adaptation is crucial for optimally developing and assessing the feasibility and acceptability of a web-based trauma psychoeducation intervention in Indonesia. The outcomes of the RCT will inform the feasibility and acceptability of web-based trauma psychoeducation in the Indonesian undergraduate student population.

Local Application of Honey for Postoperative Pain Management and Associated Outcomes Following Tonsillectomy in Children: A Systematic Review and Meta-Analysis.

This study investigates the effect of locally applied honey on pain intensity, analgesia consumption, pain relief and nighttime awakenings in children following tonsillectomy, addressing conflicting evidence and the lack of differentiation between adult and paediatric populations in previous reviews. A systematic search was conducted across multiple databases, including Cochrane Library, ClinicalTrials.gov, MEDLINE, Web of Science and Google Scholar. Randomised controlled trials (RCTs) comparing pain outcomes in children receiving honey in addition to standard treatments versus those receiving standard treatments alone were included. Pain intensity was measured with the VAS tool. Meta-analysis was performed using STATA version 14 software. Also, risk of bias and certainty of evidence were evaluated. Out of 537 articles, seven studies (n = 710) with RCT design met the inclusion criteria. The average duration for measuring pain intensity was 7.37 days. Pooled effect size showed a statistically significant reduction in pain intensity in the honey intervention group compared to the control group (WMD: -0.90, 95% CI [-1.32, -0.48], p < 0.001, I2: 92.5%; certainty of evidence: low). Also, the results demonstrated that honey significantly decreased the average time required for pain relief and analgesic consumption in the intervention group compared to the control group. One study was deemed low risk of bias, four studies were of intermediate quality and two studies were evaluated as high. While honey shows promise in reducing post-tonsillectomy pain, cautious use is advised due to the limited quality of evidence. More robust RCTs are needed to address biases and reinforce confidence in the findings.

Breastfeeding interventions and programs conducted in the Islamic Republic of Iran: a scoping review.

The purpose of this review was to identify interventions promoting breastfeeding (BF), BF practices and their outcomes in Iran. Using the PRISMA-ScR Guidelines, we searched across 14 databases for publications published between 2010 and February 2024 to identify studies published in English or Farsi language in peer-reviewed journals, using search terms 'breastfeeding', 'lactation', 'education', 'promotion', 'intervention' and 'program'. Inclusion criteria included intervention-based studies with quantitative outcomes of pregnant women/mothers receiving education, training or other intervention that promoted BF or exclusive BF. Excluded studies were protocols, those examining Iranian communities outside of Iran publications in other languages, brief communications, gray literature and qualitative studies. After screening for relevance, identified articles that met the inclusion criteria were summarized and tabulated using Rayyan QCRI software. Of the 45 identified studies, 37 used randomized-control trial designs, 20 applied theoretical frameworks or specific counseling techniques. Samples included women pregnant for the first time, mothers of babies born prematurely or with low-birth weight, adolescents, mothers who had very young children at home. Only three studies included family members. BF self-efficacy was the most popular variable to assess, which was examined in 32 studies. Almost all studies showed positive results as a result of intervention. Majority of studies were focused at the individual level. No studies were identified that assessed strategies to change routine care or policies that might facilitate BF. Identifying barriers to moving intervention content into standard of care is an important next step in the development of BF research in Iran.

Efficacy and experience of system constellations in virtual reality (VR): study protocol for a randomized controlled feasibility study

BackgroundThough evidence-based research about system constellations (SCs) appears marginal, it is applied in many psychiatric, psychological, and psychotherapeutic institutions as well as in different contexts of organizational counseling. To date, only one randomized controlled trial (RCT) has been conducted to assess the short- to long-term efficacy of SCs, which entail clients meeting at the same location in person. This study is to investigate the feasibility of a RCT investigating SCs in virtual reality (VR), and to calculate the number of clients needed for a confirmatory RCT.DesignWe will perform a prospective, monocentric, parallel-group, feasibility RCT with subsequent intervention. A total of 128 clients of 3-day group-based SC-VR seminars will be randomized to either the intervention group (IG; n = 64) or wait-list group (WLG; n = 64), which receives SCs in VR after 4 months. Feasibility and acceptability of the (1) research methodology and (2) intervention as well as the (3) estimation of effect sizes will be assessed using qualitative and quantitative data. Based on the model of a general mental health, the proposed primary outcome includes the SC-VR adherence, and the proposed secondary outcomes refer to psychological functioning (OQ-45.2), social system functioning (EXIS), psychological distress (FEP-2), motivational incongruence (INK-SF), and goal attainment (GAS). We plan to investigate the short-term efficacy at 2-week and 4-month follow-up within the RCT design (n = 128), and mid-term efficacy at 8- and 12-month follow-up for the intervention group (n = 64).DiscussionThe study is expected to be the first study on the feasibility of SC-VR. We will reflect on successfully implemented study procedures, and we will provide recommendations for changes considering the design, rationale, analyses, and interpretation of the study results where they became necessary. The discussion will conclude with an evaluation whether a confirmatory RCT on SC-VR is worth the investment of future resources, including the calculated number of clients needed based on the efficacy trends derived from this feasibility study.Trial registrationClinicalTrials.gov: ID = N CT05557890; date of registration: September 23, 2022; https://clinicaltrials.gov/ct2/show/NCT05557890.

"Family Connections", a program for relatives of people with borderline personality disorder: A randomized controlled trial.

Family members of people with Borderline Personality Disorder (BPD) often experience high levels of psychological symptoms such as depression, anxiety, or burden. Family Connections (FC) is a pioneer program designed for relatives of people with BPD, and it is the most empirically supported treatment thus far. The aim of this study was to carry out a randomized clinical trial to confirm the differential efficacy of FC versus an active treatment as usual (TAU) in relatives of people with BPD in a Spanish population sample. The sample consisted of 121 family members (82 family units) and a total of 82 patients who participated in a two-arm randomized controlled trial (RCT). The primary outcome was burden of illness. Secondary outcomes were depression, anxiety, stress, family empowerment, and quality of life. This is the first study to evaluate relatives and patients in an RCT design comparing two active treatment conditions of similar durations. Although no statistically significant differences were found between conditions. However, the adjusted posttest means for FC were systematically better than for TAU, and the effect sizes were larger in burden, stress, depression, family functioning, and quality of life in the FC intervention. Patients of caregivers who received the FC condition showed statistically significant improvements in stress, depression, and anxiety. Results indicated that FC helped both patients and relatives pointing to the importance of involving families of patients with severe psychological disorders.

Methodological insights from the EPISTOP trial to designing clinical trials in rare diseases-A secondary analysis of a randomized clinical trial.

In clinical research, the most appropriate way to assess the effect of an intervention is to conduct a randomized controlled trial (RCT). In the field of rare diseases, conducting an RCT is challenging, resulting in a low rate of clinical trials, with a high frequency of early termination and unpublished trials. The aim of the EPISTOP trial was to compare outcomes in infants with tuberous sclerosis (TSC) who received vigabatrin preventively before the seizures onset with those who received it conventionally after. The study was designed as a prospective, multicentre, randomized clinical trial. However, ethics committees at four centres did not approve this RCT design, resulting in an open-label trial (OLT) in these four centres and an RCT in the other six centres. In this paper, we re-analyse the data from the EPISTOP trial using methods to investigate the influence of allocation bias on the results of the EPISTOP trial. A bias-corrected analysis is used to support and strengthen the published results. We included a term representing the effect of selection bias as an influencing factor on the corresponding endpoint in the statistical model. Thus, the treatment effect estimates for the primary endpoint of time to first seizure and additional secondary endpoints are adjusted for the bias effect. The bias-corrected analyses for the primary endpoint show that the estimated hazard ratio and associated confidence intervals are in a very similar range (original analysis: HR 2.91, 95%-CI [1.11 to 7.67], p-value 0.0306; bias-corrected analysis: HR 2.89, 95%-CI [1.10 to 7.58], p-value 0.0316). This was also the case for the secondary endpoints. The statistical re-analysis of the raw trial data therefore supports the published results and confirms that there is no additional bias introduced by randomization, thereby increasing the value of the results. However, this highlights that this aspect needs to be considered in future trials, especially in rare diseases, to avoid additional biases in an already small sample size where it may be difficult to reach significance.

Development of a risk of bias assessment tool specifically for meta-analysis of trials for surgical site infection

Background: Surgical site infections (SSIs) significantly impact patient outcomes, with rates reaching up to 20% after surgery, leading to higher morbidity, prolonged hospital stays, and increased costs. The assessment of randomized controlled trials (RCTs) related to SSIs has been challenging due to the lack of a specialized Risk of Bias (RoB) tool, as existing tools like the RoB-2 are not surgery-specific. To address this gap, we developed an adapted SSI-specific RoB-2 tool. Methods: This tool was created through a four-stage consensus process involving surgeons, trial statisticians, and methodologists with extensive experience in international SSI trials. Results: The process identified ten critical domains relevant to assessing RCTs on SSI interventions. Of these, eight domains were prioritized as essential for the final tool, while two were considered desirable but less critical due to the challenges of blinding in surgical contexts. Conclusion: The adapted RoB-2 tool is tailored to the unique aspects of SSI trials, offering a more focused and practical means of evaluating RCT quality. It not only improves the assessment of existing studies but also guides the design of future RCTs, enhancing the quality of evidence in SSI research. The tool's application in meta-analyses will likely lead to more reliable and generalizable results, informing clinical practice and policy decisions related to SSI prevention and management.

Randomized controlled trials - The what, when, how and why.

Randomized controlled trials (RCTs) are at the top of the pyramid of evidence as they offer the best answer on the efficacy of a new treatment. RCTs are true experiments in which participants are randomly allocated to receive a certain intervention (experimental group) or a different intervention (comparison group), or no treatment at all (control or placebo group). Randomization, along with other methodological features such as blinding and allocation concealment, safeguard against biases. This review will focus on parallel group RCT design as it is the most common design in the field of Pediatric Urology. RCTs can be designed using a superiority, equivalency, or non-inferiority hypothesis, and are usually preceded by a pilot, where the trial protocol is implemented in a small number of patients, mimicking the larger, definitive study. Even though regarded as the best available option to bring out scientific data, RCTs might be prone to mislead. If RCTs are small and underpowered, a difference of even one single event between groups, may completely change the trial results. To safeguard against RCTs weakness, a fragility concept of statistical significance was developed and called the Fragility Index (FI). RCTs may not be appropriate, ethical, or feasible for all surgical interventions. They may have limitations such as prohibitive cost and unrealistic large sample sizes. Nearly 60% of surgical research questions cannot be answered by RCTs. Therefore, clinical practice should be based on the best available evidence on a given topic, regardless of the study design. However, even in these situations, conclusions drawn from observational studies must be interpreted with caution.

Effects of α-Mangostin-Loaded Self-Nanoemulsion (MG-SNE) and Physical Exercise on The Reduction of Waist Circumference in Wistar Rats

BACKGROUND : Waist circumference (WC) is a marker of intra-abdominal adipose tissue and a risk factor for cardiometabolic disease. A higher risk of coronary heart disease was associated with an increased WC. Garcinia mangostana Linn's anti-inflammatory activity would reduce abdominal fat deposition and WC. Additionally, Garcinia mangostana Linn's potential would increase in nanotechnology. AIMS : To demonstrate that WC in Wistar rats induced by an atherogenic diet can be decreased by α-Mangostin-loaded self-nanoemulsion (MG-SNE) treatment combined with physical activity. METHOD : Experimental research with Randomized Control Trial design using a total sample of 15 male white rats (Rattus novergicus strain Wistar) weighing 300 grams and aged between 6 and 8 weeks, split into 3 groups given physical exercise for 8 weeks along with 3 different doses of medication (group K received Atorvastatin 1.44 mg once; group P1 received Garcinia mangostana Linn pericarp extract, at a dose of 800 mg/kg, divided into 3 administrations; and group P2 received MG-SNE 50 mg/kg once). Waist circumference was measured using a metline, before and after treatment. RESULT : WC decreased in Groups K, P1, and P2, with deltas of -5.00±21.21 mm, -12.50±24.75 mm, and -17.50±12.58 mm. The greatest decrease in WC was P2. There was no significant difference, according to the paired test between the pre-test and posttest in all groups. The p value &gt;0.05 was determined to indicate that there were no significant differences between the groups. CONCLUSION : WC in Wistar rats induced by an atherogenic diet can be decreased by MG-SNE treatment combined with physical exercise.

Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century.

Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomized controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.

Poorly Recognized and Uncommonly Acknowledged Limitations of Randomized Controlled Trials.

Randomized controlled trials (RCTs) are a gold standard in evidence-based research. However, RCTs have limitations, among which the most commonly acknowledged is that narrow study selection criteria compromise the external validity of the findings. This article briefly touches upon this and other well-recognized limitations and presents, in greater detail, less commonly acknowledged limitations with examples from contemporary literature. Important among the less commonly acknowledged limitations are biases in RCTs of interventions to which patients cannot be blinded, weaknesses in the design of maintenance therapy RCTs, and, ubiquitously, post-randomization biases. The listed limitations notwithstanding, RCTs are still the best among research designs. What is important is to recognize the imperfections in each RCT so that the findings of the RCT can be better judged.

The impact of conditional cash transfer (CCT) on health and education in a coastal community: A randomized control trial (RCT) and regression discontinuity design (RDD)

This study evaluates the impact of the Pantawid Pamilyang Pilipino Program (4Ps), a national conditional cash transfer (CCT) on the health and education of beneficiaries in the coastal community of Maangas, Presentacion, Camarines Sur. It compares households receiving 4Ps benefits to a control group of non-recipients with similar sociodemographic characteristics to establish counterfactuals. Using a Randomized Control Trial (RCT) approach, data were collected from 157 participants in each treatment and control group through structured questionnaires. Descriptive statistics were utilized to analyze the economic profiles of respondents, revealing diverse representations. Logistic regression models unveiled significant correlations between attendance, dropout rates, and various predictor variables, notably the 4Ps program and eligibility, location, household size, and perceptions. Regarding health outcomes, the analysis demonstrates the positive impact of 4Ps membership on reducing child mortality, improving child growth, and promoting healthcare-seeking behaviors. Factors such as clinic visits, health insurance, and health beliefs also significantly influence health outcomes. RDD underscores the effectiveness of the 4Ps program in poverty alleviation, with eligibility playing a key role in enhancing income outcomes among beneficiaries. Prioritizing access to healthcare services, reinforcing the importance of regular clinic visits, and optimizing child health outcomes are crucial steps towards sustainability of the program. Tailored interventions based on enrollment status and academic performance can help prevent student attrition. Providing aid to coastal communities and embedding livelihood support programs in 4Ps can break the cycle of poverty by integrating these initiatives into the current structure of the program.

Prolotherapy in the Treatment of Sports-Related Tendinopathies: A Systematic Review of Randomized Controlled Trials.

As sports have increased in popularity, the incidence of tendinopathy has also grown dramatically. Nonoperative techniques and treatments used to address these pathologies continue to evolve and improve. One such treatment, prolotherapy (PrT), has become increasingly popular and may provide patients with an alternative nonoperative treatment option. To review high-quality randomized controlled trials (RCTs) that analyzed PrT treatments for the most common tendinopathies. Specifically, this review aims to provide meaningful data regarding methods and outcomes for each condition treated and guide professionals who are considering PrT as a treatment option. Systematic review; Level of evidence, 2. All RCTs published in English between January 1, 1980, and July 30, 2021, and reported in Embase, Medline, and Web of Science databases were reviewed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. After the initial search, a total of 3264 articles were identified. Studies analyzing sports medicine injuries and musculoskeletal pathologies using an RCT design were included, while case-reports, case-studies, reviews, and observational studies were excluded. Two independent researchers reviewed the search results, and conflicts were resolved by discussion of inclusion and exclusion criteria among all authors. The articles' quality was evaluated using the Cochrane tool for assessing the risk of bias. Statistical analysis and graphical representations were performed using SPSS Version 28.00. A total of 20 articles, including 1136 patients, met the inclusion criteria and were included in the study. Overall, in 85% of the studies, PrT was found to be effective in the treatment of tendinopathy. Specifically, PrT was superior to or as effective as the control in 83% (10/12) of the studies analyzing lateral epicondylitis (LE) and rotator cuff (RC) tendinopathies and in 88% (7/8) of the studies on plantar fasciitis (PF), Osgood-Schlatter disease (OSD), and Achilles tendinosis (AT). LE, RC, and PF tendinopathies were the most studied conditions (17/20 studies), while AT and OSD were the least studied (3/20 studies). Of the studies, 95% (19/20) used dextrose solutions, with only 1 using solutions of 2.5% phenol, 25% glycerin, and 25% dextrose in sterile water. Our systematic review suggests that PrT appears to be a promising alternative treatment for common tendinopathies. Most studies used a hypertonic dextrose solution. Even though further, larger randomized controlled trials comparing PrT with other orthobiologics would be beneficial, based on this review, sports medicine physiciansmay safely pursue PrT as an additional component of conservative treatment.