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.

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.

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.

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.

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.

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.

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.

Distribution-Free Approach to the Design and Analysis of Randomized Stroke Trials With the Modified Rankin Scale.

BACKGROUND: Many methods have been suggested for analyzing the modified Rankin Scale (mRS). However, there lacks a unified approach to analysis and sample size determination that properly uses the ordinal nature of the data. We propose a simple method for CI estimation and corresponding sample size determination. METHODS: We quantify treatment effect by the win probability (WinP) that a randomly selected patient in the treatment group has an equal or a better mRS score than a patient in the control group. Thus, a win probability of 0.5 means no effect, likened to a draw in competitive sports. We estimate the win probability and its SE based on the ranks of mRS scores, where tied scores are handled by average ranks. Corresponding methods for hypothesis testing, CI estimation, and sample size determination are derived. The methods are evaluated with a simulation study based on real data from 10 randomized stroke trials that used mRS as the outcome measure. RESULTS: Simulation results demonstrated that the methods performed very well in terms of CI coverage, tail errors, and assurance to achieving the prespecified precision. Because the methods are very simple, we implemented them in an Excel spreadsheet, requiring only user inputs on frequencies of mRS scores in 2 comparison groups. CONCLUSIONS: Sound statistical methods are important for the success of randomized stroke trials. The proposed methods and associated spreadsheet should prove useful for stroke researchers in the planning and analysis of randomized trials. Meta-analysis has also been made easy for trials with ordinal scores.

Treatment of carotid stenosis in asymptomatic, nonoctogenarian, standard risk patients with stenting versus endarterectomy trials.

OBJECTIVE: Asymptomatic carotid stenosis is the most frequent indication for carotid endarterectomy (CEA) in the United States. Published trials and guidelines support CEA indications in selected patients with longer projected survival and when periprocedural complications are low. Transfemoral carotid artery stenting with embolic protection (CAS) is a newer treatment option. The objective of this study was to compare outcomes in asymptomatic, nonoctogenarian patients treated with CAS vs CEA. METHODS: Patient-level data was analyzed from 2544 subjects with ≥70% asymptomatic carotid stenosis who were randomized to CAS or CEA in addition to standard medical therapy. One trial enrolled 1091 (548 CAS, 543 CEA) and another enrolled 1453 (1089 CAS, 364 CEA) asymptomatic patients less than 80 years old (upper age eligibility). Independent neurologic assessment and routine cardiac enzyme screening were performed. The prespecified, primary composite endpoint was any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization. RESULTS: There was no significant difference in the primary endpoint between CAS and CEA (5.3% vs 5.1%; hazard ratio, 1.02; 95% confidence interval, 0.7-1.5; P = .91). Periprocedural rates for the components are (CAS vs CEA): any stroke (2.7% vs 1.5%; P = .07), myocardial infarction (0.6% vs 1.7%; P = .01), death (0.1% vs 0.2%; P = .62), and any stroke or death (2.7% vs 1.6%; P = .07). After this period, the rates of ipsilateral stroke were similar (2.3% vs 2.2%; P = .97). CONCLUSIONS: In a pooled analysis of two large randomized trials of CAS and CEA in asymptomatic, nonoctogenarian patients, CAS achieves comparable short- and long-term results to CEA.

Effect of Adjusted Antiplatelet Therapy on Preventing Ischemic Events After Stenting for Intracranial Aneurysms.

BACKGROUND AND PURPOSE: This study tests whether patients with unruptured intracranial aneurysm who underwent stent placement benefitted from platelet function monitoring-guided adjustment of antiplatelet therapy. METHODS: We conducted a randomized, open-label, parallel group, assessor-blinded trial. Patients with unruptured intracranial aneurysm who underwent stent placement were assigned in a 1:1 ratio to receive either drug adjustment (patients who had high on-treatment platelet reactivity to antiplatelet therapy on the basis of platelet function monitoring [monitoring group]) or conventional therapy (without monitoring and drug adjustment [conventional group]). The second monitoring was performed 14 days after randomization in patients with drug adjustment. The primary outcome was the composite frequency of ischemic stroke, transient ischemic attack, stent thrombosis, urgent revascularization, and cerebrovascular death within 7 days after stent implantation. The safety outcome was the composite frequency of major, minor, or minimal bleeding within 1 month after stent implantation. RESULTS: In total, 314 patients were included (n=157 per group). The primary combined outcome occurred in 19 patients (12.1%) in the conventional group and 8 patients (5.1%) in the monitoring group (hazard ratio, 0.39 [95% CI, 0.17-0.92]; P=0.03). Ischemic stroke occurred at a lower frequency in the monitoring group compared with that in the conventional group (4.5% versus 12.1%; hazard ratio, 0.34 [95% CI, 0.14-0.83]; P=0.01), which drove the overall primary combined outcome. The safety outcome occurred in the monitoring group (7.0%) and in the conventional group (1.9%; hazard ratio, 3.87 [95% CI, 1.06-14.14]; P=0.03). A significant difference was observed in the frequency of minor or minimal bleeding events between the two groups (monitoring group versus conventional group, 6.4% versus 1.3%; P=0.02) but not in the frequency of major bleeding events between the two groups. CONCLUSIONS: Platelet function monitoring-guided antiplatelet therapy reduces thromboembolic events in patients with unruptured intracranial aneurysm after stent placement, significantly enhancing minor or minimal bleeding events but not major bleeding events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03989557.

Incentive delivery timing and follow-up survey completion in a prospective cohort study of injured children: a randomized experiment comparing prepaid and postpaid incentives.

BACKGROUND: Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study's objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. METHODS: We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. RESULTS: The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. CONCLUSIONS: Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.

The influence of ageism on stereotypical attitudes among allied health students in Japan: a group comparison design.

BACKGROUND: Ageism is a serious problem in medical care. The importance of ageism-related education for students has been emphasized. To determine the most effective approach to ageism-related education for allied health students, this study examined ageism among this group of students, with the hypothesis that ageism was expressed not only toward elderly adults but also toward individuals other than elderly adults. METHODS: A questionnaire survey was conducted among 154 allied health students in Japan. The questionnaire involved tree drawings to evaluate the drawer's personality and a measurement of the participants' ageism. There were two display conditions for tree drawing. In the elderly display condition, participants were informed that the drawer was an elderly person, and in a control condition, participants were not informed of the drawer's age. Participants were randomly assigned to each condition and were required to evaluate the drawer's personality based on 5 personality traits. After the evaluation, all participants were required to complete the Japanese short version of the Fraboni Scale of Ageism (FSA-J). RESULTS: The participants were 123 allied health students, 61 of whom were in the elderly display condition and 62 of whom were in the control condition. Based on the mean score on the FSA-J (M = 29.80), we divided the participants into a low-FSA-J group (N = 64) and a high-FSA-J group (N = 59). There was no significant difference between the display conditions on the FSA-J score. In the high-FSA-J groups, the control condition evaluated the drawer's personality as more timid than did the elderly display condition (F = 4.26, df = 1, 119). For negligence, the high-FSA-J group evaluated the drawer's personality as more negligent than did the low-FSA-J group (F = 4.08). For broad interests, the main effects of condition and groups were significant (F = 4.23). CONCLUSIONS: The results suggested that ageism indicated a negative evaluation not only of elderly adults but also of individuals other than elderly adults, and students with negative ageism might evaluate the elderly drawer more positively. We have discussed the possibility that negative ageism among allied health students in Japan might underlie these positive stereotypes.

Efficacy of an online course in developing competency for prescribing balanced diet by medical students: A non - inferiority trial.

BACKGROUND: In the COVID era, medical education has been hit hard. Paradoxically, the need for health professionals has increased. Online methods are being widely used, but its efficacy is rarely measured. OBJECTIVES: This study was conducted to find the efficacy of an online course in developing competency among medical students to prescribe balanced diet. METHODS: An online module was hosted at https://drzinia.moodlecloud.com/. A noninferiority trial was conducted among voluntary participants of the third MBBS students, in 2019. Stratified block randomization was done, so that ten students were allocated to the intervention arm of online sessions and ten students were allocated to the control arm of classroom sessions. Pretest assessments, seven assessments related to sessions conducted, and a postassessment were done. Generalized estimating equations were done to adjust for the effects of other confounders and see whether the intervention was a significant determinant of ability to prescribe balanced diet. RESULTS: Baseline variables were comparable in the two groups. The pretest scores were not significantly different in the two groups. The mean total marks scored by the online group (47.33/70) was not significantly different (t=0.68; p=0.50) from that of the class room group (45.70/70). The posttest scores were significantly higher than the pretest scores. Ninety-percent of students in the online course agreed that they could effectively learn through an online course. CONCLUSION: Online teaching is effective to learn the prescription of balanced diet. Similar efforts in other domains can make medical education evidence based in the current scenario.

Effectiveness of the clinical decision support tool ESR eGUIDE for teaching medical students the appropriate selection of imaging tests: randomized cross-over evaluation.

OBJECTIVES: To evaluate ESR eGUIDE-the European Society of Radiology (ESR) e-Learning tool for appropriate use of diagnostic imaging modalities-for learning purposes in different clinical scenarios. METHODS: This anonymized evaluation was performed after approval of ESR Education on Demand leadership. Forty clinical scenarios were developed in which at least one imaging modality was clinically most appropriate, and the scenarios were divided into sets 1 and 2. These sets were provided to medical students randomly assigned to group A or B to select the most appropriate imaging test for each scenario. Statistical comparisons were made within and across groups. RESULTS: Overall, 40 medical students participated, and 31 medical students (78%) answered both sets. The number of correctly chosen imaging methods per set in these 31 paired samples was significantly higher when answered with versus without use of ESR eGUIDE (13.7 ± 2.6 questions vs. 12.1 ± 3.2, p = 0.012). Among the students in group A, who first answered set 1 without ESR eGUIDE (11.1 ± 3.2), there was significant improvement when set 2 was answered with ESR eGUIDE (14.3 ± 2.5, p = 0.013). The number of correct answers in group B did not drop when set 2 was answered without ESR eGUIDE (12.4 ± 2.6) after having answered set 1 first with ESR eGUIDE (13.0 ± 2.7, p = 0.66). CONCLUSION: The clinical decision support tool ESR eGUIDE is suitable for training medical students in choosing the best radiological imaging modality in typical scenarios, and its use in teaching radiology can thus be recommended. KEY POINTS: • ESR eGUIDE improved the number of appropriately selected imaging modalities among medical students. • This improvement was also seen in the group of students which first selected imaging tests without ESR eGUIDE. • In the student group which used ESR eGUIDE first, appropriate selection remained stable even without the teaching tool.

Autologous bone-marrow mononuclear stem cell therapy in patients with stroke: a meta-analysis of comparative studies.

BACKGROUND: There is a need to promote recovery after stroke with novel therapeutic interventions. Of them, bone-marrow mononuclear cell (BM-MNC) therapy offers promising outcomes in preclinical and clinical models. AIMS: To investigate the efficacy and safety of BM-MNCs versus traditional medical care of stroke patients. A meta-analysis was conducted involving controlled prospective studies and randomized clinical trials (RCTs) which investigated the changes in the scores of neurological functions (the National Institutes of Health Stroke Scale [NIHSS]), the indices of functional recovery (the Barthel Index [BI] and the modified Rankin scale [mRS]) at 3 and 6 month post-transplantation. A total of nine studies (five RCTs) recruited 469 stroke patients (65.5% males, 49.25% received the intervention). There were no significant differences in NIHSS, BI, or mRS scores after 3 months of follow-up. However, the BI indices of BM-MNCs-receiving patients improved significantly after 6 months (standardized mean difference = 1.17, 95% confidence interval, 0.23 to 2.10, P = 0.01) as compared to traditional treatment. The risk of mortality and adverse events and the proportion of patients with favorable outcomes (mRS ≤ 3) were similar in both groups. CONCLUSION: Both the BM-MNCs and medical stroke treatment have similar outcomes in terms of safety and short-term efficacy, while the effect of therapy is significant only after 6 months. More well-designed, large sized RCTs are needed to confirm the efficacy of stem cell therapy over long periods of follow-up.

Using automated pump-delivery devices to reduce the incidence of excessive fluid administration during pediatric dental surgery: a randomized-controlled trial.

PURPOSE: The harms caused by excessive perioperative intravenous (IV) fluid administration are both well recognized and avoidable. The purpose of this study was to compare the incidence of excess intraoperative fluid administration in pediatric dental surgery patients when either an automated pump-delivery device or a manual gravity-drip device is used. METHODS: We randomly assigned American Society of Anesthesiologists physical status I and II pediatric dental surgery patients to receive IV fluid via either a manual gravity-drip or automated pump-delivery device. Prior to each case, the attending anesthesiologist determined the target volume of maintenance IV fluid to be administered based on patient weight, estimated fluid deficits, and expected case length. The intraoperative IV fluid delivered was determined at the end of the case by the change in the IV bag weight. The primary outcome was the proportion of procedures that delivered ≥ 10% of the target IV fluid volume. RESULTS: We recruited 105 children aged two to 12 yr (n = 49 in the automated pump-delivery device; n = 53 in the manual gravity-drip device). The proportion of excessive fluid administration was 8/49 (16%) in the automated pump-delivery device group compared with 33/53 (62%) in the gravity-drip group (relative risk of excessive fluid administration, 0.26; 95% confidence interval, 0.13 to 0.51; P < 0.001). CONCLUSION: Intraoperative fluid administration using an automated pump-delivery device decreased the incidence of excessive IV fluid administration in pediatric dental surgery patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03312452); registered 17 October 2017.

RéSUMé: OBJECTIF: Les effets néfastes causés par une administration liquidienne intraveineuse (IV) périopératoire excessive sont à la fois bien connus et évitables. L'objectif de cette étude était de comparer l'incidence d'administration liquidienne peropératoire excessive chez les patients pédiatriques de chirurgie dentaire lors de l'utilisation d'une pompe à perfusion automatique vs un système goutte à goutte manuel par gravité. MéTHODE: Nous avons randomisé des patients pédiatriques de chirurgie dentaire de statut physique I et II selon l'American Society of Anesthesiologists à recevoir des liquides intraveineux soit par un système goutte à goutte manuel par gravité ou via une pompe à perfusion automatique. Avant chaque cas, l'anesthésiologiste en charge a déterminé le volume cible de liquide IV de maintien à administrer selon le poids du patient, les déficits liquidiens estimés, et la durée anticipée du cas. La quantité de liquides IV peropératoires administrés était déterminée à la fin du cas par le changement du poids du sac de liquide IV. Le critère d'évaluation principal était la proportion d'interventions ayant administré ≥ 10 % du volume liquidien IV cible. RéSULTATS: Nous avons recruté 105 enfants âgés de deux à 12 ans (n = 49 dans le groupe pompe automatique; n = 53 dans le groupe goutte à goutte manuel). La proportion d'administration liquidienne excessive était de 8/49 (16 %) dans le groupe pompe automatique, comparativement à 33/53 (62 %) dans le groupe goutte à goutte (risque relatif d'administration liquidienne excessive, 0,26; intervalle de confiance 95 %, 0,13 à 0,51; P < 0,001). CONCLUSION: L'administration liquidienne peropératoire à l'aide d'une pompe a réduit l'incidence d'administration liquidienne IV excessive chez des patients pédiatriques de chirurgie dentaire. ENREGISTREMENT DE L'éTUDE: ww.clinicaltrials.gov (NCT03312452); enregistrée le 17 octobre 2017.

Interference Spreading through Random Subcarrier Allocation Technique and Its Error Rate Performance in Cognitive Radio Networks.

In this letter, we investigate the idea of interference spreading and its effect on bit error rate (BER) performance in a cognitive radio network (CRN). The interference spreading phenomenon is caused because of the random allocation of subcarriers in an orthogonal frequency division multiplexing (OFDM)-based CRN without any spectrum-sensing mechanism. The CRN assumed in this work is of underlay configuration, where the frequency bands are accessed concurrently by both primary users (PUs) and secondary users (SUs). With random allocation, subcarrier collisions occur among the carriers of primary users (PUs) and secondary users (SUs), leading to interference among subcarriers. This interference caused by subcarrier collisions spreads out across multiple subcarriers of PUs rather than on an individual PU, therefore avoiding high BER for an individual PU. Theoretical and simulated signal to interference and noise ratio (SINR) for collision and no-collision cases are validated for M-quadrature amplitude modulation (M-QAM) techniques. Similarly, theoretical BER performance expressions are found and compared for M-QAM modulation orders under Rayleigh fading channel conditions. The BER for different modulation orders of M-QAM are compared and the relationship of average BER with interference temperature is also explored further.

[Development of a Method for Assignment Control in Randomized Controlled Trials].

Randomized controlled trials (RCT) are the most reliable study design for causality estimation in medical research. Proper implementation of the process of randomization is necessary to ensure the reliability of RCT. In order to do so, 1) generation of randomization sequence, 2) allocation concealment, and 3) allocation must be properly implemented. Methods such as the central secretariat method, the envelope method, and the sequentially numbered container method are adopted to secure proper implementation. For investigator-initiated clinical research and relatively small-scale clinical research, the envelope method and the sequentially numbered container method are often adopted because of budgetary reasons, but these methods do not assure the implementation of proper RCT. Therefore, we designed an assignment management note system as a new method to manage the assignment of RCT that can be implemented in small scale clinical research. In this paper, we compare the assignment management note system with the conventional method from the viewpoint of the procedure necessary for the proper implementation of RCT, and discuss the advantages and limitations of the assignment management note system.

Merged block randomisation: A novel randomisation procedure for small clinical trials.

BACKGROUND/AIMS: Randomisation in small clinical trials is a delicate matter, due to the tension between the conflicting aims of balanced groups and unpredictable allocations. The commonly used method of permuted block randomisation has been heavily criticised for its high predictability. This article introduces merged block randomisation, a novel and conceptually simple restricted randomisation design for small clinical trials (less than 100 patients per stratum). Merged block randomisation is a simple procedure that can be carried out without need for a computer. Merged block randomisation is not restricted to 1:1 randomisation, but is readily applied to unequal target allocations and to more than two treatment groups. METHODS: The position of merged block randomisation on the spectrum of balance and predictability is investigated in a simulation study, in two common situations: a single-centre study and a multicentre study (with sampling stratified per centre). Methods included for comparison were permuted block randomisation, Efron's biased coin design, the maximal procedure, the block urn design and the big stick design. RESULTS: Compared to permuted block randomisation with blocks of size 4, merged block randomisation has the same maximum tolerated imbalance and is thus as impervious to chronological bias, with the added benefit of being less predictable. Each method in the study takes a different position on the balance/determinism spectrum, and none was uniformly best. Merged block randomisation was either less predictable or more balanced than the other methods, in all simulation settings. CONCLUSION: Merged block randomisation is a versatile restricted randomisation method that outperforms permuted block randomisation and is a good choice for small clinical trials where imbalance is a main concern, especially in multicentre trials where the number of patients per centre may be small.

Understanding Long-Term Trajectories in Web-Based Happiness Interventions: Secondary Analysis From Two Web-Based Randomized Trials.

BACKGROUND: A critical issue in understanding the benefits of Web-based interventions is the lack of information on the sustainability of those benefits. Sustainability in studies is often determined using group-level analyses that might obscure our understanding of who actually sustains change. Person-centric methods might provide a deeper knowledge of whether benefits are sustained and who tends to sustain those benefits. OBJECTIVE: The aim of this study was to conduct a person-centric analysis of longitudinal outcomes, examining well-being in participants over the first 3 months following a Web-based happiness intervention. We predicted we would find distinct trajectories in people's pattern of response over time. We also sought to identify what aspects of the intervention and the individual predicted an individual's well-being trajectory. METHODS: Data were gathered from 2 large studies of Web-based happiness interventions: one in which participants were randomly assigned to 1 of 14 possible 1-week activities (N=912) and another wherein participants were randomly assigned to complete 0, 2, 4, or 6 weeks of activities (N=1318). We performed a variation of K-means cluster analysis on trajectories of life satisfaction (LS) and affect balance (AB). After clusters were identified, we used exploratory analyses of variance and logistic regression models to analyze groups and compare predictors of group membership. RESULTS: Cluster analysis produced similar cluster solutions for each sample. In both cases, participant trajectories in LS and AB fell into 1 of 4 distinct groups. These groups were as follows: those with high and static levels of happiness (n=118, or 42.8%, in Sample 1; n=306, or 52.8%, in Sample 2), those who experienced a lasting improvement (n=74, or 26.8% in Sample 1; n=104, or 18.0%, in Sample 2), those who experienced a temporary improvement but returned to baseline (n=37, or 13.4%, in Sample 1; n=82, or 14.2%, in Sample 2), and those with other trajectories (n=47, or 17.0%, in Sample 1; n=87, or 15.0% in Sample 2). The prevalence of depression symptoms predicted membership in 1 of the latter 3 groups. Higher usage and greater adherence predicted sustained rather than temporary benefits. CONCLUSIONS: We revealed a few common patterns of change among those completing Web-based happiness interventions. A noteworthy finding was that many individuals began quite happy and maintained those levels. We failed to identify evidence that the benefit of any particular activity or group of activities was more sustainable than any others. We did find, however, that the distressed portion of participants was more likely to achieve a lasting benefit if they continued to practice, and adhere to, their assigned Web-based happiness intervention.