BACKGROUND: The proper interpretation of a study\'s results requires both excellent understanding of good methodological practices and deep knowledge of prior results, aided by the availability of effect sizes.
METHODS: This review takes the form of an expository essay exploring the complex and nuanced relationships among statistical significance, clinical importance, and effect sizes.
RESULTS: Careful attention to study design and methodology will increase the likelihood of obtaining statistical significance and may enhance the ability of investigators/readers to accurately interpret results. Measures of effect size show how well the variables used in a study account for/explain the variability in the data. Studies reporting strong effects may have greater practical value/utility than studies reporting weak effects. Effect sizes need to be interpreted in context. Verbal summary characterizations of effect sizes (e.g., \"weak\", \"strong\") are fundamentally flawed and can lead to inappropriate characterization of results. Common language effect size (CLES) indicators are a relatively new approach to effect sizes that may offer a more accessible interpretation of results that can benefit providers, patients, and the public at large.
CONCLUSIONS: It is important to convey research findings in ways that are clear to both the research community and to the public. At a minimum, this requires inclusion of standard effect size data in research reports. Proper selection of measures and careful design of studies are foundational to the interpretation of a study\'s results. The ability to draw useful conclusions from a study is increased when investigators enhance the methodological quality of their work.

OBJECTIVE: Temporomandibular disorder (TMD) is the term used to describe a pathology (dysfunction and pain) in the masticatory muscles and temporomandibular joint (TMJ). There is an apparent upward trend in the publication of dental research and a need to continually improve the quality of research. Therefore, this study was conducted to analyse the use of sample size and effect size calculations in a TMD randomised controlled trial.
METHODS: The period was restricted to the full 5 years, i.e., papers published in 2019, 2020, 2021, 2022, and 2023. The filter article type-\"Randomized Controlled Trial\" was used. The studies were graded on a two-level scale: 0-1. In the case of 1, sample size (SS) and effect size (ES) were calculated.
RESULTS: In the entire study sample, SS was used in 58% of studies, while ES was used in 15% of studies.
CONCLUSIONS: Quality should improve as research increases. One factor that influences quality is the level of statistics. SS and ES calculations provide a basis for understanding the results obtained by the authors. Access to formulas, online calculators and software facilitates these analyses. High-quality trials provide a solid foundation for medical progress, fostering the development of personalized therapies that provide more precise and effective treatment and increase patients\' chances of recovery. Improving the quality of TMD research, and medical research in general, helps to increase public confidence in medical advances and raises the standard of patient care.

Background Small-group discussions (SGDs) are pivotal in medical education, facilitating the development of critical thinking, communication skills, and teamwork. However, traditional SGDs face challenges such as scalability and maintaining student engagement. This study aims to evaluate the \"Distribute, Discuss, and Develop\" (3D) method for enhancing learning outcomes in medical education. Methods A single-blinded interventional study was conducted with 125 first-year Bachelor of Medicine and Bachelor of Surgery students, who were divided into intervention and control groups through random assignment. The intervention group employed the 3D method across two thematic units: hematology and muscle nerve physiology. The study assessed learning outcomes using pre- and posttests, class-average normalized gain (\"g\"), and feedback questionnaires to capture student perceptions of interaction, communication enhancement, and session summarization. Results The intervention group showed significantly improved learning outcomes in both thematic units, with larger effect sizes (hematology: 1.55; muscle nerve physiology: 1.4) compared to the control group. The normalized gain \"g\" indicated a medium effectiveness level for the intervention group in both themes, suggesting enhanced learning. Feedback questionnaires revealed higher satisfaction levels within the intervention group regarding interaction, communication skills, and session summarization. Conclusions The 3D method addresses the challenges faced by traditional SGDs, providing a scalable and engaging approach to medical education. By fostering more effective student-centered learning, the method enhances the comprehension of complex physiological concepts and improves communication skills. The 3D method significantly improves learning outcomes, interaction, and communication skills in medical education. This innovative approach to SGDs offers a promising strategy for enhancing the educational experience in medical schools, supporting the development of more articulate and professionally competent medical graduates.

UNASSIGNED: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality.
UNASSIGNED: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 μg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 μg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes.
UNASSIGNED: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy.
UNASSIGNED: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study.
UNASSIGNED: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

The growing research interest in the relationship between health insurance and pharmaceutical innovation is driven by their significant impact on healthcare optimization and pharmaceutical development. The existing literature, however, lacks consensus on this relationship and provides no evidence of the magnitude of a correlation. In this context, this study employs meta-analysis to explore the extent to which health insurance affects pharmaceutical innovation. It analyzes 202 observations from 14 independent research samples, using the regression coefficient of health insurance on pharmaceutical innovation as the effect size. The results reveal that there is a strong positive correlation between health insurance and pharmaceutical innovation (r = 0.367, 95% CI = [0.294, 0.436]). Public health insurance exhibits a stronger promoting effect on pharmaceutical innovation than commercial health insurance. The relationship between health insurance and pharmaceutical innovation is moderated by the country of sample origin, data range, journal type, journal impact factor, type of health insurance, and research perspective. Our research findings further elucidate the relationship mechanism between health insurance and pharmaceutical innovation, providing a valuable reference for future explorations in pharmaceutical fields.

Objectives: Amphetamines are a preferred treatment for attention-deficit/hyperactivity disorder (ADHD), with the dextroamphetamine transdermal system (d-ATS) providing an alternative to oral formulations. A pivotal trial of d-ATS in children and adolescents with ADHD met primary and key secondary endpoints. This analysis reports additional endpoints and safety findings from the pivotal trial and evaluates effect size and number needed to treat (NNT) for d-ATS. Methods: In this study, a 5-week, open-label dose-optimization period (DOP) preceded a 2-week, randomized, crossover double-blind treatment period (DBP). Eligible patients received d-ATS 5 mg during the DOP, with weekly evaluations for increase to 10, 15, and 20 mg (equivalent to labeled doses of 4.5, 9, 13.5, and 18 mg/9 hours, respectively) until reaching and maintaining the optimal dose, which was utilized for the DBP. Secondary endpoints included assessment of Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV), Conners\' Parent Rating Scale Revised Short Form (CPRS-R:S), and Clinical Global Impression (CGI) scores. NNT was calculated for ADHD-RS-IV and CGI-Improvement (CGI-I). Safety assessments included treatment-emergent adverse events (TEAEs) and dermal safety. Results: In total, 110 patients entered the DOP, with 106 patients randomized (DBP). During the DBP, the least-squares mean (95% confidence interval) difference for d-ATS versus placebo in ADHD-RS-IV total score was -13.1 (-16.2 to -10.0; p < 0.001), with effect size of 1.1 and NNT of 3 for ADHD-RS-IV remission, ≥30% improvement, and ≥50% improvement. Significant differences between placebo and d-ATS were also observed for CPRS-R:S and CGI-I scales (p < 0.001), with NNT of 2 for CGI-I response. Most TEAEs were mild or moderate, with three leading to study discontinuation in the DOP and none in the DBP. No patients discontinued due to dermal reactions. Conclusions: d-ATS was effective in treating ADHD in children and adolescents, meeting all secondary endpoints, with a large effect size and NNT of 2-3 to achieve a clinically meaningful response. d-ATS was safe and well tolerated, with minimal dermal reactions. Clinical Trial Registration: NCT01711021.

To assess the language used by systematic review authors to emphasize that statistically nonsignificant results show meaningful differences. To determine whether the magnitude of these treatment effects was distinct from nonsignificant results that authors interpreted as not different.
We screened Cochrane reviews published between 2017 and 2022 for statistically nonsignificant effect estimates that authors presented as meaningful differences. We classified interpretations qualitatively and assessed them quantitatively by calculating the areas under the curve of the portions of confidence intervals exceeding the null or a minimal important difference, indicating one intervention\'s greater effect.
In 2,337 reviews, we detected 139 cases where authors emphasized meaningful differences in nonsignificant results. Authors commonly used qualifying words to express uncertainty (66.9%). Sometimes (26.6%), they made absolute claims about one intervention\'s greater benefit or harm without acknowledging statistical uncertainty. The areas under the curve analyses indicated that some authors may overstate the importance of nonsignificant differences, whereas others may overlook meaningful differences in nonsignificant effect estimates.
Nuanced interpretations of statistically nonsignificant results were rare in Cochrane reviews. Our study highlights the need for a more nuanced approach by systematic review authors when interpreting statistically nonsignificant effect estimates.

BACKGROUND: The traumatic brain injury (TBI) Intensive Evaluation and Treatment Program (IETP) is an innovative modality for delivering evidence-based treatments in a residential, inpatient format to special operational forces service members and veterans with mild TBI. IETPs provide bundled evidence-based assessment, treatment, referral, and case management in concordance with the existing guidelines for mild TBI and commonly co-occurring comorbidities. To date, there has been no formal characterization or evaluation of the IETP to understand the determinants of implementation across the system of care. The goal of our partnered evaluation initiative (PEI) with an operational partner, the Physical Medicine and Rehabilitation National Program Office, is to facilitate the full implementation of the IETP across all 5 Veterans Health Administration TBI-Centers of Excellence (TBI-COE) and to inform minimum standards while supporting the unique characteristics of each site.
OBJECTIVE: This IETP partnered evaluation will describe each of the 5 TBI-COE IETP services and state of implementation to identify opportunities for adaptation and scale, characterize the relationship between patient characteristics and clinical services received, evaluate the outcomes for participants in the IETP, and inform ongoing implementation and knowledge translation efforts to support IETP expansion. In alignment with the goals of the protocol, ineffective treatment components will be targeted for deimplementation.
METHODS: A 3-year concurrent mixed methods evaluation using a participatory approach in collaboration with the operational partner and TBI-COE site leadership will be conducted. Qualitative observations, semistructured focus groups, and interviewing methods will be used to describe IETP, stakeholder experiences and needs, and suggestions for IETP implementation. Quantitative methods will include primary data collection from patients in the IETP at each site to characterize long-term outcomes and patient satisfaction with treatment and secondary data collection to quantitatively characterize patient-level and care system-level data. Finally, data sets will be triangulated to share data findings with partners to inform ongoing implementation efforts.
RESULTS: Data collection began in December 2021 and is currently ongoing. The results and deliverables will inform IETP characterization, evaluation, implementation, and knowledge translation.
CONCLUSIONS: The results of this evaluation seek to provide an understanding of the determinants affecting the implementation of IETPs. Service member, staff, and stakeholder insights will inform the state of implementation at each site, and quantitative measures will provide options for standardized outcome measures. This evaluation is expected to inform national Physical Medicine and Rehabilitation Office policies and processes and knowledge translation efforts to improve and expand the IETP. Future work may include cost evaluations and rigorous research, such as randomized controlled trials.
UNASSIGNED: DERR1-10.2196/44776.

The sample size calculation is an important step in designing randomised controlled trials. For a trial comparing a control and an intervention group, where the outcome is binary, the sample size calculation requires choosing values for the anticipated event rates in both the control and intervention groups (the effect size), and the error rates. The Difference ELicitation in TriAls guidance recommends that the effect size should be both realistic, and clinically important to stakeholder groups. Overestimating the effect size leads to sample sizes that are too small to reliably detect the true population effect size, which in turn results in low achieved power. In this study, we use the Delphi approach to gain consensus on what the minimum clinically important effect size is for Balanced-2, a randomised controlled trial comparing processed electroencephalogram-guided \'light\' to \'deep\' general anaesthesia on the incidence of postoperative delirium in older adults undergoing major surgery.
Delphi rounds were conducted using electronic surveys. Surveys were administered to two stakeholder groups: specialist anaesthetists from a general adult department in Auckland City Hospital, New Zealand (Group 1), and specialist anaesthetists with expertise in clinical research, identified from the Australian and New Zealand College of Anaesthetist\'s Clinical Trials Network (Group 2). A total of 187 anaesthetists were invited to participate (81 from Group 1 and 106 from Group 2). Results from each Delphi round were summarised and presented in subsequent rounds until consensus was reached (>70% agreement).
The overall response rate for the first Delphi survey was 47% (88/187). The median minimum clinically important effect size was 5.0% (interquartile range: 5.0-10.0) for both stakeholder groups. The overall response rate for the second Delphi survey was 51% (95/187). Consensus was reached after the second round, as 74% of respondents in Group 1 and 82% of respondents in Group 2 agreed with the median effect size. The combined minimum clinically important effect size across both groups was 5.0% (interquartile range: 3.0-6.5).
This study demonstrates that surveying stakeholder groups using a Delphi process is a simple way of defining a minimum clinically important effect size, which aids the sample size calculation and determines whether a randomised study is feasible.

This study aimed to compare the functional connectivity (FC) assessed during acute stress and recovery after stress using the Montreal imaging stress task (MIST) in adults in their 20s and 30s with Korean Perceived Stress Scale (PSS) scores between 15 and 19 points inclusive. Four seed networks, including the salience network, default mode network, frontoparietal network, and dorsal attention network, were specified to extract the results. Healthy male and female adults who were required to make an effort to relieve stress were exposed to acute stress tasks, and the most common FCs were observed in the salience network, default mode network, and frontoparietal network during the stress and recovery phases. Compared to the stress phase, the increased effect size was significantly different in the recovery phase. In the stress phase, characteristically common FCs were observed in the dorsal attention network. During the recovery period, Salience network (Anterior Insula, R) and Salience network (anterior cingulate cortex, ACC)/Salience network (rostral prefrontal cortex, RPFC), Salience network (AInsula) and Salience network (RPFC), and Default Mode network (posterior cingulate) cortex, PCC) and fronto-parietal network (lateral prefrontal cortex, LPFC) FC were characteristically observed.