Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

BACKGROUND: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. METHODS: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. RESULTS: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. CONCLUSIONS: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. REGISTRATION: URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

Saddlepoint p-values for a class of location-scale tests.

The main idea of this paper is to approximate the exact p-value of a class of non-parametric, two-sample location-scale tests. In this paper, the most famous non-parametric two-sample location-scale tests are formulated in a class of linear rank tests. The permutation distribution of this class is derived from a random allocation design. This allows us to approximate the exact p-value of the non-parametric two-sample location-scale tests of the considered class using the saddlepoint approximation method. The proposed method shows high accuracy in approximating the exact p-value compared to the normal approximation method. Moreover, the proposed method only requires a few calculations and time, as in the case of the simulated method. The procedures of the proposed method are clarified through four sets of real data that represent applications for a number of different fields. In addition, a simulation study compares the proposed method with the traditional methods to approximate the exact p-value of the specified class of the non-parametric two-sample location-scale tests.

Adaptive Randomization Method to Prevent Extreme Instances of Group Size and Covariate Imbalance in Stroke Trials.

BACKGROUND: A recent review of randomization methods used in large multicenter clinical trials within the National Institutes of Health Stroke Trials Network identified preservation of treatment allocation randomness, achievement of the desired group size balance between treatment groups, achievement of baseline covariate balance, and ease of implementation in practice as critical properties required for optimal randomization designs. Common-scale minimal sufficient balance (CS-MSB) adaptive randomization effectively controls for covariate imbalance between treatment groups while preserving allocation randomness but does not balance group sizes. This study extends the CS-MSB adaptive randomization method to achieve both group size and covariate balance while preserving allocation randomness in hyperacute stroke trials. METHODS: A full factorial in silico simulation study evaluated the performance of the proposed new CSSize-MSB adaptive randomization method in achieving group size balance, covariate balance, and allocation randomness compared with the original CS-MSB method. Data from 4 existing hyperacute stroke trials were used to investigate the performance of CSSize-MSB for a range of sample sizes and covariate numbers and types. A discrete-event simulation model created with AnyLogic was used to dynamically visualize the decision logic of the CSSize-MSB randomization process for communication with clinicians. RESULTS: The proposed new CSSize-MSB algorithm uniformly outperformed the CS-MSB algorithm in controlling for group size imbalance while maintaining comparable levels of covariate balance and allocation randomness in hyperacute stroke trials. This improvement was consistent across a distribution of simulated trials with varying levels of imbalance but was increasingly pronounced for trials with extreme cases of imbalance. The results were consistent across a range of trial data sets of different sizes and covariate numbers and types. CONCLUSIONS: The proposed adaptive CSSize-MSB algorithm successfully controls for group size imbalance in hyperacute stroke trials under various settings, and its logic can be readily explained to clinicians using dynamic visualization.

Strengths, challenges, and strategies for implementing pragmatic multicenter randomized controlled trials (RCTs): example of the Personalized Citizen Assistance for Social Participation (APIC) trial.

BACKGROUND: Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d'Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults' health, social participation, and life satisfaction. METHODS: A multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document. RESULTS: Aged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing. CONCLUSION: Knowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions. TRIAL REGISTRATION: NCT03161860; Pre-results. Registered on May 22, 2017.

Effectiveness of the Cooled Radiofrequency Ablation of Genicular Nerves in Patients with Chronic Knee Pain Due to Osteoarthritis: A Double-Blind, Randomized, Controlled Study.

Background: Increasing evidence supporting the clinical effectiveness of cooled radiofrequency ablation (RFA) therapy for genicular nerves in patients with chronic knee osteoarthritis (OA) exists. However, no study has been conducted to eliminate the potential influence of a placebo effect associated with this procedure. Therefore, we evaluated the efficacy of cooled RFA compared with a sham procedure in patients with painful knees due to OA. Methods: In this double-blind, randomized, controlled study, participants were randomly assigned to receive cooled RFA of the knee (cooled RFA group, n = 20) or a sham procedure (sham group, n = 20). The primary outcome was the proportion of successful responders at the three-month follow-up. The secondary outcomes were successful responders at one and six months; pain intensity of the knee; functional status; medication; and satisfaction at one, three, and six months after the procedures. Results: For the primary outcome, the successful responder rate was significantly higher in the cooled RFA group (76.5%) than in the sham group (33.3%) (p = 0.018). For the secondary outcome, more successful responders were observed in the cooled RFA group than in the sham group at one and six months after the procedure (p = 0.041 and 0.007, respectively). The decreased knee pain intensity was maintained throughout the six-month follow-up period in the cooled RFA group. No differences were observed in functional status, medication change, or satisfaction in both groups. Conclusions: The cooled RFA of genicular nerves offers significant pain relief and surpasses the effects attributable to a placebo.

A practical guide to estimating treatment effects in patients with rheumatic diseases using real-world data.

OBJECTIVE: Randomized controlled trials are considered the gold standard in study methodology. However, due to their study design and inclusion criteria, these studies may not capture the heterogeneity of real-world patient populations. In contrast, the lack of randomization and the presence of both measured and unmeasured confounding factors could bias the estimated treatment effect when using observational data. While causal inference methods allow for the estimation of treatment effects, their mathematical complexity may hinder their application in clinical research. METHODS: We present a practical, nontechnical guide using a common statistical package (Stata) and a motivational simulated dataset that mirrors real-world observational data from patients with rheumatic diseases. We demonstrate regression analysis, regression adjustment, inverse-probability weighting, propensity score (PS) matching and two robust estimation methods. RESULTS: Although the methods applied to control for confounding factors produced similar results, the commonly used one-to-one PS matching method could yield biased results if not thoroughly assessed. CONCLUSION: The guide we propose aims to facilitate the use of readily available methods in a common statistical package. It may contribute to robust and transparent epidemiological and statistical methods, thereby enhancing effectiveness research using observational data in rheumatology.

Histological Evaluation of Alveolar Ridge Preservation Using Different Bone Grafts: Clinical Study Analysis Part II.

To compare histologically the percentage of bone formation 12-20 weeks after ridge augmentation using 2 different techniques. Tooth loss is associated with 3-dimensional bone remodeling and ridge atrophy. Ridge preservation procedures can prevent alveolar bone volume loss. Different techniques and materials are used to preserve the alveolar ridge. Computer-generated randomization software was used to assign 2 ridge preservation techniques for 11 extraction sites. In group I, type I bovine Achilles tendon collagen plugs with bioactive resorbable calcium apatite crystals (CPCAC) were placed, and in group II, cortico-cancellous bone chips (CCBC) mix and an expanded polytetrafluoroethylene (ePTFE) barrier membrane were placed. The histomorphometric studies were performed using a computer-based image analysis system (ImageJ 1.4, National Institute of Health, Bethesda, Md) to calculate the pixel area of bone tissue and the remaining bone graft material. The histomorphometric data were analyzed using a Student t test to compare the measurements between the 2 experimental groups. This parametric statistical test was employed to determine if there were any statistically significant differences in the quantitative histological parameters between the groups. The sockets that received CPCAC showed a lower (31.89%) percentage of native bone surface area compared with the CCBC group (43.87%). However, the difference was not statistically significant (P < .05). In addition, the CPCAC group showed evidence of foreign-body reaction. The CCBC graft covered with an ePTFE barrier may induce more bone formation with minimal inflammation in an extraction socket compared with a collagen plug with calcium apatite crystals. In addition, histological analysis of the CPCAC graft showed evidence of foreign-body reaction, which indicates a negative clinical impact.

The Association between Message Framing and Intention to Vaccinate Predictive of Hepatitis A Vaccine Uptake.

As ongoing, sporadic outbreaks of hepatitis A virus (HAV) infections present public health challenges, it is critical to understand public perceptions about HAV, especially regarding vaccination. This study examines whether message framing changes the intention to vaccinate against HAV and self-reported vaccine behavior. Using a randomized controlled trial (N = 472) in February 2019 via Amazon Mechanical Turk, participants were randomized to one of four HAV vaccination message groups or a no-message control group. The message groups varied in their emphasis on the nature of outcomes (gain versus loss) and for whom (individual versus collective). The message frames were compared by intention to vaccinate, differences in message characteristics, and behavioral determinants. There was no difference in intention to vaccinate between gain- versus loss-framed messages (MD = 0.1, 95% CI = -0.1, 0.3) and individual- versus collective-framed messages (MD = 0.1, 95% CI = -0.1, 0.3). The intention to vaccinate against HAV in the no-message control group was very similar to that in the message groups. However, gain-framed messages were rated more positively in valence than loss-framed messages (MD = -0.5, 95% CI = -0.7, -0.3), which may be helpful for cultivating a positive public perception of HAV vaccination. The study also highlights the importance of comparing message frames to a no-message control in designing health communication messaging promoting HAV vaccination.

Effectiveness of virtual reality in relieving anxiety and controlling hemodynamics during oral surgery under local anesthesia: A prospective randomized comparative study.

It was the aim of the study to evaluate the contribution of a relaxing immersive experience with virtual reality (VR) goggles in reducing patient anxiety related to wisdom tooth extraction under local anesthesia. A prospective randomized comparative study in consecutive patients scheduled for bilateral wisdom tooth extraction under local anesthesia was carried out between March and December 2022. Both sides were operated upon in the same surgery, but on one side VR goggles were applied (VR), while on the other they were not (noVR). Anxiety was evaluated both subjectively (State-Trait Anxiety Inventory [STAI] and visual analogue scale [VAS]) and objectively (measuring heart rate, blood pressure [BP] and blood oxygen saturation) before (T1) and after each surgical step (T2VR and T2noVR). The study sample consisted of 27 patients: 9 men and 18 women, with an average age of 25.8 ± 6.5 years (range: 18-43). Anxiety as assessed by the STAI and VAS decreased from T1 to T2 (p < 0.001 and p < 0.001, respectively), although to a similar degree regardless of whether VR was used or not. Heart rate showed significant differences influenced by RV exposure (p = 0.013): it increased +2.5 ± 8.8 bpm in the control group and decreased -2.22 ± 7.55 bpm with VR (p = 0.013). Both minimum and maximum BP after surgery were significantly higher in the noVR group (p = 0.002 and p = 0.040, respectively). Regarding minimum BP, VR proved more effective among male patients (p = 0.057) and on starting the procedure using VR (p = 0.055). The results provided evidence of meaningful control of the hemodynamic variables, but less predictable performance in the subjective evaluation of anxiety.

Why Are We Weighting? Understanding the Estimates From Propensity Score Weighting and Matching Methods.

BACKGROUND: Propensity score methods are used in observational studies to compensate for the lack of random allocation by balancing measured baseline characteristics between treated and untreated patients. We sought to explain the treatment effect estimates derived from different propensity score methods. METHODS: We performed a retrospective analysis of long-term mortality after single internal mammary artery versus bilateral internal mammary artery (BIMA) conduit in 47 984 index isolated coronary artery bypass grafting procedures from 1992 to 2014 in the Northern New England Cardiovascular Disease Study Group registry using multivariable Cox regression, 1:1 propensity score matching, inverse probability weighting (IPW) among the treated, and IPW among the overall population treatment estimates. RESULTS: The mean duration of follow-up was 13.2 (interquartile range, 7.4-17.7) years. In multivariable Cox regression, the adjusted hazard ratio for mortality was 0.83 (95% CI, 0.75-0.92) in patients receiving BIMA compared with a single internal mammary artery. The 1:1 propensity matched (hazard ratio, 0.79 [95% CI, 0.69-0.91]) and IPW among the treated (hazard ratio, 0.83 [95% CI, 0.75-0.92]) estimates showed a protective treatment effect of BIMA use on mortality. However, the IPW estimate of treatment effect for the overall population showed an increased risk of mortality after BIMA that was not statistically significant (hazard ratio, 1.08 [95% CI, 0.94-1.24]). CONCLUSIONS: While the multivariable Cox regression, 1:1 propensity matching, and IPW treatment effect in the treated estimates demonstrate that BIMA was associated with a statistically significantly decreased risk of mortality, the IPW treatment effect in the average study population showed an increased risk of mortality associated with BIMA that was not statistically significant. This is attributed to the different populations (weighted to look like the overall study population versus treated group) represented by the 2 IPW approaches. Determining how the study population is balanced is a large driver of the treatment effect. Ultimately, the treatment effect estimate desired should drive the choice of the propensity score method.

Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment-elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size. METHODS: This is an open-label, prospective, multicenter, randomized study. We enrolled patients aged 18 to 75 years who were within 12 hours of symptom onset of ST-segment-elevation myocardial infarction and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline intravenously before PCI. The primary end point was Thrombolysis in Myocardial Infarction flow grade 2 to 3 or grade 3 in the infarct-related artery 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance 5 days after randomization. The safety end point was major bleeding (Bleeding Academic Research Consortium ≥3) during 30-day follow-up. RESULTS: A total of 283 patients were screened from 8 centers and 200 were randomized (median age, 58.5 years; 14% female). The median symptom to thrombolysis time was 252.5 (interquartile range, 142.8-423.8) minutes and thrombolysis to coronary arteriography was 50.0 (interquartile range, 37.0-66.0) minutes. Patients randomized to r-SAK compared with normal saline more often had Thrombolysis in Myocardial Infarction flow grade 2 to 3 (69.0% versus 29.0%; P<0.001) and Thrombolysis in Myocardial Infarction flow grade 3 (51.0% versus 18.0%; P<0.001) and had smaller infarct size (21.91±10.84% versus 26.85±12.37%; P=0.016). There was no increase in major bleeding (r-SAK, 1.0% versus control, 3.0%; P=0.616). CONCLUSIONS: A single bolus r-SAK before primary PCI for ST-segment-elevation myocardial infarction improves infarct-related artery patency and reduces infarct size without increasing major bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05023681.

Interpreting Randomized Controlled Trials.

This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial's sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and true simple or stratified random sampling, as executed in surveys. We argue that group-specific statistics, such as a median survival time estimate for a treatment arm in an RCT, have limited meaning as estimates of larger patient population parameters. In contrast, random allocation between interventions facilitates comparative causal inferences about between-treatment effects, such as hazard ratios or differences between probabilities of response. Comparative inferences also require the assumption of transportability from a clinical trial's convenience sample to a targeted patient population. We focus on the consequences and limitations of randomization procedures in order to clarify the distinctions between pairs of complementary concepts of fundamental importance to data science and RCT interpretation. These include internal and external validity, generalizability and transportability, uncertainty and variability, representativeness and inclusiveness, blocking and stratification, relevance and robustness, forward and reverse causal inference, intention to treat and per protocol analyses, and potential outcomes and counterfactuals.

Characteristics of baseline frequency data in spinal RCTs do not suggest widespread non-random allocation.

BACKGROUND: Recent signs of fraudulent behaviour in spine RCTs have queried the integrity of trials in the field. RCTs are particularly important due to the weight they are accorded in guiding treatment decisions, and thus, ensuring RCTs' reliability is crucial. This study investigates the presence of non-random baseline frequency data in purported RCTs published in spine journals. METHODS: A PubMed search was performed to obtain all RCTs published in four spine journals (Spine, The Spine Journal, the Journal of Neurosurgery Spine, and European Spine Journal) between Jan-2016 and Dec-2020. Baseline frequency data were extracted, and variable-wise p values were calculated using the Pearson Chi-squared test. These p values were combined for each study into study-wise p values using the Stouffer method. Studies with p values below 0.01 and 0.05 and those above 0.95 and 0.99 were reviewed. Results were compared to Carlisle's 2017 survey of anaesthesia and critical care medicine RCTs. RESULTS: One hundred sixty-seven of the 228 studies identified were included. Study-wise p values were largely consistent with expected genuine randomized experiments. Slightly more study-wise p values above 0.99 were observed than expected, but a number of these had good explanations to account for that excess. The distribution of observed study-wise p values was more closely matched to the expected distribution than those in a similar survey of the anaesthesia and critical care medicine literature. CONCLUSION: The data surveyed do not show evidence of systemic fraudulent behaviour. Spine RCTs in major spine journals were found to be consistent with genuine random allocation and experimentally derived data.

Say it right: measuring the impact of different communication strategies on the decision to get vaccinated.

BACKGROUND: Vaccine hesitancy is a concerning menace to the control of vaccine-preventable diseases. Effective health communication could promote an overall understanding of the importance, risks, and benefits of vaccination and reduce vaccine hesitancy. METHODS: In this survey, four fictitious newspaper articles addressing an emerging bogus disease and its vaccine were randomly assigned to participants. The first version focused on information about the disease; the second was akin to the first, including a case description and image. The third version focused on vaccine safety/efficacy; the fourth version was like the third, including a case description and image. After reading a single version of the article, participants responded if they would take the vaccine and if they would vaccinate their children. We used chi-squared tests for comparisons and investigated interactions with vaccine-hesitant attitudes. RESULTS: We included 5233 participants between August/2021 and January/2022; 790 were caregivers of a child ≤ 5 years old, and 15% had prior vaccine hesitancy. Although most declared intention to take the vaccine, the percentage was highest among those exposed to the newspaper article focusing on the vaccine safety/efficacy with the case description and picture (91%; 95% confidence interval 89-92%), and lowest among participants exposed to the article focusing on the disease with no case description (84%; 95% confidence interval 82-86%). Similar trends were observed in the intention of offspring vaccination. We found evidence of effect modification by vaccine-hesitant attitudes, with a higher impact of communication focusing on vaccine safety/efficacy compared to that focusing on disease characteristics among hesitant participants. CONCLUSION: Communication strategies focusing on different aspects of the disease-vaccine duet may impact vaccine hesitancy, and storytelling/emotive imagery descriptions may improve risk perception and vaccine uptake. Moreover, the effect of message framing strategies may differ according to previous vaccine hesitant attitudes.

A scoping review described diversity in methods of randomization and reporting of baseline balance in stepped-wedge cluster randomized trials.

OBJECTIVES: In stepped-wedge cluster randomized trials (SW-CRTs), clusters are randomized not to treatment and control arms but to sequences dictating the times of crossing from control to intervention conditions. Randomization is an essential feature of this design but application of standard methods to promote and report on balance at baseline is not straightforward. We aimed to describe current methods of randomization and reporting of balance at baseline in SW-CRTs. STUDY DESIGN AND SETTING: We used electronic searches to identify primary reports of SW-CRTs published between 2016 and 2022. RESULTS: Across 160 identified trials, the median number of clusters randomized was 11 (Q1-Q3: 8-18). Sixty-three (39%) used restricted randomization-most often stratification based on a single cluster-level covariate; 12 (19%) of these adjusted for the covariate(s) in the primary analysis. Overall, 50 (31%) and 134 (84%) reported on balance at baseline on cluster- and individual-level characteristics, respectively. Balance on individual-level characteristics was most often reported by condition in cross-sectional designs and by sequence in cohort designs. Authors reported baseline imbalances in 72 (45%) trials. CONCLUSION: SW-CRTs often randomize a small number of clusters using unrestricted allocation. Investigators need guidance on appropriate methods of randomization and assessment and reporting of balance at baseline.

Ensayos aleatorizados publicados por instituciones ubicadas en Perú: estudio bibliométrico del periodo 2000 a 2022

Objetivo: Caracterizar la producción científica de ensayos aleatorizados por instituciones ubicadas en Perú del 01 de enero de 2000 al 30 de diciembre de 2022. Materiales y Métodos: Estudio bibliométrico, se revisaron dos bases de datos (MEDLINE y SciELO). Se incluyeron artículos originales en la que al menos un autor consignó como filiación una institución ubicada en Perú. Se caracterizó la producción científica según: área temática, participación de instituciones ubicadas en Perú, revistas científicas en las que se publicaron los artículos, y aprobación de los estudios por un Comité de Ética en Investigación (CEI). Resultados: Se analizó un total de 402 artículos, se evidenció una tendencia creciente de la producción científica, pasando de seis en el año 2000 a 39 en el año 2021, el área temática predominante es la infecciosa, las dos primeras instituciones con mayor número de ensayos aleatorizados pertenecen al sector educación, 189 (47,0%) artículos fueron publicados en revistas de Estados Unidos, en 37 (9,2%) artículos no se consigna información de aspectos éticos o no se declara explícitamente si fue o no aprobado por un CEI. Conclusión: Hay una tendencia creciente de la producción científica sobre este diseño de estudio, el área temática predominante es la infecciosa, las instituciones peruanas más productivas pertenecen al sector educación, cerca de la mitad de los artículos fueron publicados en revistas de Estados Unidos, y en una décima parte de los artículos no se señala explícitamente si el estudio fue o no aprobado por un CEI.

Objetive: To characterize the scientific production of randomized trials by institutions located in Peru from January 1, 2000 to December 30, 2022. Materials and methods: Bibliometric study, two databases (MEDLINE and SciELO) were reviewed. Original articles were included in which at least one author stated an institution located in Peru as affiliation. Scientific production was characterized according to: thematic area, participation of institutions located in Peru, scientific journals in which the articles were published, and approval of the studies by a Research Ethics Committee (REC). Results: A total of 402 articles were analyzed, a growing trend in scientific production was evidenced, going from six in the year 2000 to 39 in the year 2021, the predominant thematic area is infectious, the first two institutions with the highest number of randomized trials belong to the education sector, 189 (47.0%) articles were published in journals in the United States, in 37 (9.2%) articles there is no information on ethical aspects or it is not explicitly stated whether or not it was approved by a CEI. Conclusions: There is a growing trend of scientific production on this study design, the predominant thematic area is infectious, the most productive Peruvian institutions belong to the education sector, about half of the articles were published in journals in the United States, and in a tenth part of the articles do not explicitly state whether or not the study was approved by an REC.

The weighted log-rank tests based on stratified clustered survival data: saddle-point p-values and confidence intervals.

Clinical studies sometimes provide clustered data with censored failure times. A crucial factor of the randomized design that lessens selection bias is the random allocation rule. Given this, the weighted rank tests' p-values for stratified survival clustered sampling based on the random allocation rule are approximated using the double saddle-point approximation technique. For tests of significance and confidence intervals for the treatment effect, this approximation can be utilized. Through simulation experiments, the accuracy of the saddle-point approximation is examined by comparing saddle-point and normal approximations to the exact underlying permutation distribution.

Comparison of virtual reality and physical simulation training in first-year radiography students in South America.

INTRODUCTION: The aim of this study was to comparatively evaluate the learning outcomes achieved by first-year radiography students educated with either virtual reality (VR) simulation training or physical simulation training. The implementation of VR has been proposed to enhance learning in radiography students and provide a more effective and efficient approach to simulation. However, the learning outcomes achieved with this approach have not been widely investigated. METHODS: Through stratified randomisation, 188 radiography students were allocated to one of two matched groups: a VR group (using Virtual Medical Coaching's Radiography simulation) and a physical simulation group (using Philips' X-ray equipment). Both groups were taught 31 radiography views over one 25-week semester. Both groups were assessed in an Objective Structured Clinical Examination (OSCE), using actors as patients in a physical X-ray environment. Assessment was conducted by assigning objective count scores for five assessment criteria. RESULTS: The VR group achieved shorter OSCE duration and fewer errors in moving equipment and patient positioning: these results were statistically significant (P < 0.00). There was no significant difference in the frequency of errors in radiographic exposure setting between the VR and the physical simulation group. The current findings concur with the limited number of published studies concerning VR simulation in radiography. CONCLUSIONS: The results of this study demonstrated superior effectiveness and efficiency in the VR group. This provides preliminary evidence to introduce VR simulation in the host institution and provide evidence that it may be possible to replace the use of physical simulation across other years of the degree. Further research investigating these possibilities is warranted.

Intraoral clinical examinations of pediatric patients with anticipatory anxiety and situational fear facilitated by therapy dog assistance: A pilot RCT.

OBJECTIVE: To evaluate whether the presence of a certified therapy dog specially trained for working in a dental setting may facilitate dental care of anxious pediatric patients. METHODS: The Norwegian Regional Committee for Medical and Health Research Ethics approved a randomized cross-over trial with a study sample of n = 16 children aged between 6 and 12 years. The trial was registered on clinicaltrials.gov. Pediatric patients referred to specialist care at the Public Dental Service Competence Center of Northern Norway (TkNN) because of anxiety were invited to partake in the trial. Study participants met twice for an intraoral examination by a specialist pediatric dentist. Per random allocation, a therapy dog team was present in the clinic operatory during the clinical examination on the first or the second visit. The primary outcome was the assessment of patient compliance during the intraoral examination (yes/no). Secondary outcomes were measurements of child satisfaction and anxiety using the CFSS-DS scale (Dental subscale of Children's Fear Survey Schedule) completed by a parent/guardian. Supplementary outcomes were salivary cortisol level, heart rate variability, and skin conductance. RESULTS: Ten boys and six girls (mean age 8.5) were recruited. All completed both clinical visits and demonstrated full compliance while undergoing a dental examination. All study participants and guardians reported great satisfaction. The salivary cortisol level reduction during the clinical examination on the first visit decreased by 30% in the presence of the therapy dog and 20% without, while the decrease during the clinical examination on the second visit was 29% in the presence of the therapy dog and 3% without. Within the limitations of the experimental setup, the electrophysiological measurements were unreliable in the current study population. CONCLUSION: Dog-assisted therapy in a dental care setting appears to have a positive effect on children with dental anxiety or children that avoid dental care.