Random Sequence Allocation Research Articles

The HYsteroscopic Miscarriage MaNagement (HYMMN) pilot randomized-controlled trial

ObjectiveTo evaluate the feasibility of performing a full-scale, adequately powered, multi-center randomized controlled trial (RCT) assessing the effectiveness of office hysteroscopy (OH) for the treatment of retained pregnancy tissue (RPT) after miscarriage, compared with standard treatment (ST) (expectant/medical/surgical), on future pregnancy outcome. Study designSingle-center pilot RCT performed at Birmingham Women’s Hospital, UK. Patients opting for non-surgical miscarriage management at ≤14 weeks gestation who wanted to conceive as soon as possible were recruited and offered a transvaginal ultrasound scan (TVUS) eight weeks later to check for the presence of RPT. Patients with RPT were randomized in a 1:1 ratio using a computer-generated online random allocation sequence to either OH (performed using the TruClear 5.0 hysteroscopic tissue retrieval system) or ST (the type of which was recommended based on symptoms, urinary pregnancy test and scan findings). Results158 participants were approached for inclusion into the trial, of which 149 (94.3%) agreed. Of the 126 that underwent TVUS, RPT were diagnosed in 42 patients (33.3%). 21 patients were randomized to OH, of whom 18 underwent the procedure because three fell pregnant after their TVUS. OH was deemed acceptable to all patients without any serious complications. 21 patients were randomized to ST where 16 patients (76%) were recommended expectant management and five (24%) were recommended surgical management. 115 patients (91%) were able to provide pregnancy data, however, the study was not powered to show a clinically significant difference. ConclusionA full-scale, adequately powered, randomized clinical trial investigating OH against ST for the treatment of RPT following miscarriage is clinically relevant and feasible owing to high rates of participation, acceptability and satisfaction and low rates of attrition associated with the proposed interventions.

Analysis of Pain and Effectiveness in Digital Block of the First Toe Using Syringe vs. Carpule: Frost's H vs. Modified Frost's H Randomized Clinical Trial.

Background: Currently, there is no scientific evidence regarding pain in the anesthetic block of the first toe according to the method of application. However, clinical evidence has highlighted the use of the carpule due to the low pain it causes during the administration of the anesthetic. Most studies on anesthesia and pain, especially using the carpule and distraction methods, belong to the field of dentistry. Objective: To compare the pain and effectiveness between the anesthetic block of the first toe using a carpule and syringe with Frost's H technique and the modified Frost's H technique. Method: A total of 564 subjects were selected and divided into four groups. Subjects were subjected to experimental conditions (randomization through the Random Allocation Software program 2.0), and divided into group 1 = 138 subjects, corresponding to the block with syringe and Frost's H, group 2 = 141 subjects, corresponding to the syringe group and modified Frost's H, group 3 = 141 subjects, corresponding to the carpule group and modified Frost's H, and group 4 = 144 subjects, corresponding to the carpule group and Frost's H. The same researcher generated the random allocation sequence, enrolled the participants, and assigned them to the interventions. Each subject was unaware of the anesthetic procedure assigned by the researcher. Outcome parameters were pain after anesthetic infiltration and its effectiveness. Results: The anesthetic block with carpule showed a lower pain score compared to the anesthetic block with syringe (2.8 vs. 5.3; p < 0.001). However, when analyzing effectiveness, a higher efficacy rate was obtained in the anesthetic blocks performed using the modified Frost's H technique (97.5% vs. 88.1%; p < 0.001). Conclusions: The anesthetic block with carpule and the modified Frost's H technique is less painful and more effective than the traditional anesthetic block.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation

Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Comparative effectiveness of Propolis with chlorhexidine mouthwash on gingivitis – a randomized controlled clinical study

BackgroundTo assess and compare the effectiveness of propolis mouthwash with chlorhexidine mouthwash in the reduction of plaque and gingivitis.MethodsA single centre, latin-square cross-over, double masked, randomized controlled clinical trial was conducted on 45 chronic generalized gingivitis subjects who were chosen from the dental clinic of MAHSA University, Malaysia. A total of 45 subjects were randomly assigned into one of the three different groups (n = 15 each) using a computer-generated random allocation sequence: Group A Propolis mouthwash; Group B Chlorhexidine mouthwash; and Group C Placebo mouthwash. Supragingival plaque and gingival inflammation were assessed by full mouth Plaque index (PI) and gingival index (GI) at baseline and after 21 days. The study was divided into three phases, each phase lasted for 21 days separated by a washout period of 15 days in between them. Groups A, B and C were treated with 0.2% Propolis, Chlorhexidine, and Placebo mouthwash, respectively, in phase I. The study subjects were instructed to use the assigned mouthwash twice daily for 1 min for 21 days. On day 22nd, the subjects were recalled for measurement of PI and GI. After phase I, mouthwash was crossed over as dictated by the Latin square design in phase II and III.ResultsAt baseline, intergroup comparison revealed no statistically significant difference between Groups A, B and C (p > 0.05). On day 21, one-way ANOVA revealed statistically significant difference between the three groups for PI (p < 0.001) and GI (p < 0.001). Bonferroni post-hoc test showed statistically significant difference between Propolis and Chlorhexidine mouthwash (P < 0.001), with higher reduction in the mean plaque and gingival scores in propolis group compared to chlorhexidine and placebo groups.ConclusionsPropolis mouthwash demonstrated significant improvement in gingival health and plaque reduction. Thus, it could be used as an effective herbal mouthwash alternative to chlorhexidine mouthwash.Trial registrationThe trial was retrospectively registered on 25/07/2019 at clinicaltrials.gov and its identifier is NCT04032548.

Metabolic, cognitive and neuromuscular responses to different multidirectional agility-like sprint protocols in elite female soccer players – a randomised crossover study

PurposeResistance to fatigue is a key factor in injury prevention that needs to be considered in return-to-sport (RTS) scenarios, especially after severe knee ligament injuries. Fatigue should be induced under game-like conditions. The SpeedCourt (SC) is a movement platform for assessing multidirectional sprint performance, typical of game-sports, due to change-of-direction movements in response to a visual stimulus. Designing adequate fatigue protocols requires the suitable arrangement of several loading variables such as number of intervals, sprint distance or work/relief ratio (W:R). Therefore, this study analysed the acute fatigue effects of different SC protocols on metabolic load, cognitive function and neuromuscular performance.MethodsEighteen female soccer players (mean ± SD; age: 23.1 ± 4.6 years) of the 1st German Division participated in this randomised, crossover study. Using a random allocation sequence, players completed four volume-equated protocols differing in W:R and sprint distance per interval (P1:12 × 30 m, W:R = 1:2 s; P2:12 × 30 m, W:R = 1:3 s; P3:18 × 20 m, W:R = 1:2 s; P4:18 × 20 m, W:R = 1:3 s). Pre- and post-exercise, metabolic load was measured per blood lactate concentration (BLaC), cognitive function per reaction time (RT), and neuromuscular performance including multiple rebound jumps (MRJ height, primary outcome variable; Reactive Strength Index, RSI) and 5 m sprint times (SP5).ResultsRepeated-measures ANOVA revealed significant main time effects (p < .05) with improved performance post-exercise in RT (504 vs. 482 ms, d = 1.95), MRJ height (24.0 vs. 24.8 cm, d = 0.77), RSI (1.39 vs. 1.43, d = 0.52), and SP5 (1.19 vs. 1.17 s, d = 0.56). There was significant main time (p < .001) and time x protocol interaction effects in BLaC (p < .001). P1 induced higher BLaC values (4.52 ± 1.83 mmol/L) compared to P2 (3.79 ± 1.83 mmol/L; d = 0.74) and P4 (3.12 ± 1.83 mmol/L; d = 1.06), whereas P3 (4.23 ± 1.69 mmol/L) elicited higher BLaC values compared to P4 (d = 0.74).ConclusionAll protocols caused an improved cognitive function and neuromuscular performance. The former may be related to enhanced noradrenergic activation or exercise specificity which induced an improved stimulus processing. The latter may be explained by a possible post-activation performance enhancement effect on jump and sprint performance. A shorter relief duration in W:R as opposed to sprint distance per interval produced higher BLaC values. The protocols may serve as reference data for improved RTS decision-making in elite female soccer players.Trial registrationDeutsches Register Klinischer Studien (DRKS), No.: DRKS00033496, Registered 19. Februar 2024, Retrospectively Registered.

Low-Level Laser Therapy for Improvement of In Vitro Fertilization Outcomes in Patients with Recurrent Implantation Failure: A Randomized Clinical Trial.

Introduction: Numerous strategies have been investigated for addressing recurrent implantation failure (RIF) and enhancing endometrial receptivity, yet agreement on the optimal intervention remains elusive. Our investigation endeavors to assess the effect of low-level laser therapy (LLLT) on pregnancy outcomes in individuals who have undergone a minimum of three unsuccessful embryo transfer cycles (ET). Methods: In our randomized single-blinded clinical trial, we enrolled thirty females with a medical history of RIF who were eligible for frozen-thawed embryo transfer (FET). Through a random allocation sequence, the participants were divided into two groups. The LLLT was performed one cycle before blastocyst transfer in 15 cases using a New Age BIOLASER device (New Age Co., Italy) with a 900-milliwatt power output and an 850-nm wavelength. The irradiation sessions were conducted transabdominal on the hypogastric area. The considered outcomes were biochemical pregnancy, identified by a positive blood pregnancy test, and clinical pregnancy, confirmed through visualization of the gestational sac using ultrasonography. Results: The mean age of the subjects was 34.17 years, and they had undergone three to seven previous embryo transfers. There was no significant difference in basic characteristics between the group undergoing laser treatment and the control group. However, the laser-treated group exhibited elevated rates of both biochemical and clinical pregnancies compared to the control group (46.7% vs. 33.3%; P==0.710 and 33.3% vs. 20.0%; P=0.682 respectively). Conclusion: To our knowledge, this study represents the first single-blinded randomized clinical trial to assess the effectiveness of LLLT pretreatment in individuals with RIF. The findings propose that LLLT may potentially enhance biochemical and clinical pregnancy rates among RIF patients.

How well do orthodontic RCTs comply with CONSORT guidelines?

To assess the changes in compliance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized controlled trials (RCTs) in four orthodontic journals. To assess whether reporting of randomization, concealment, and blinding has improved. Electronic hand searching was undertaken to identify orthodontic RCTs published in four orthodontic journals from January 2016 to June 2017 (T1) and from January 2019 to June 2020 (T2). The journals were the American Journal of Orthodontics and Dentofacial Orthopaedics (AJO-DO), Angle Orthodontist (AO), European Journal of Orthodontics (EJO), and Journal of Orthodontics (JO). Each item on the CONSORT checklist was scored as either reported, not reported, or not applicable for each paper reporting an RCT. The study included 69 papers reporting an RCT published in T1 and 64 RCTs published in T2. The median CONSORT score in T1 was 48.7% (interquartile range [IQR] 27.6%, 68.6%) and 67% in T2 (IQR 43.9%, 79.5%). This increase was statistically significant (P = 0.001) and largely attributable to improved reporting in AO (P = 0.016) and EJO (P = 0.023). Reporting did not change significantly in AJO-DO (P = 0.13) or in JO (P = 1.0). Reporting of random allocation sequence generation (OR 2.09; 95% CI 1.01, 4.29) and concealment of allocation (OR 2.27%, 95% CI 1.12, 4.57) were significantly higher in T2 compared with T1. Reporting of blinding did not change significantly. Overall reporting of CONSORT items in reports of orthodontic RCTs published in the AJO-DO, AO, EJO, and JO, improved significantly from 2016-17 to 2019-20. This could be improved further by authors, journal referees, and editors adhering to the guidelines.

Removal of Contaminated Personal Protective Equipment With and Without Supervision. A Randomized Crossover Simulation-Based Study.

Personal protective equipment (PPE) reduces the risk of pathogens reaching the skin and clothing of health care personnel. We hypothesize that doffing PPE following verbal instructions by a supervisor is more effective in reducing contamination compared with doffing without verbal instructions. Our primary aim was to determine contamination rates with and without supervised doffing. The secondary aim was to determine the number and localization of contaminated body sites and PPE removal times in both groups. Staff members of Bnai Zion Medical Center participated in this single-center, randomized simulation study (NCT05008627). Using a crossover design, all participants donned and doffed the PPE twice, once under guidance from a trained supervisor and then independently without supervision (group A), or vice versa (group B). Participants were randomized to either group A or B using a computer-generated random allocation sequence. The PPE was "contaminated" with Glo Germ on the thorax, shoulders, arms, hands, legs, and face shield. After doffing the PPE, the participant was examined under ultraviolet light to detect traces of contamination. The following variables were collected: contamination rates, the number and localization of contaminated body sites, and PPE doffing time. Forty-nine staff members were included. In group A, the contamination rate was significantly lower (8% vs. 47%; χ 2 = 17.19; p < 0.001). The sites most frequently contaminated were the neck and hands. Mean PPE doffing time under verbal instructions was significantly longer [mean (SD): 183.98 (3.63) vs. 68.43 (12.75) seconds, P < 0.001] compared with unsupervised doffing. In a simulated setting, PPE doffing following step-by-step verbal instructions from a trained supervisor reduces the rate of contamination but prolongs doffing time. These findings could have important implications for clinical practice and could further protect health care workers against contamination from emerging and high-consequence pathogens.

The Use of Wound Infiltration for Postoperative Pain Management after Breast Cancer Surgery: A Randomized Clinical Study

(1) Background: The present study aims to evaluate the reduction of postoperative pain in breast surgery using a series of local analgesics, which were infiltrated into the wound; (2) Methods: Envelopes containing allocation were prepared prior to the study. The patients involved were randomly assigned to the groups of local anesthesia infiltration (Group A) or normal pain management with intravenous analgesics (Group B). The random allocation sequence was generated using computer-generated random numbers. The normally distributed continuous data were expressed as the means (SD) and were assessed using the analysis of variance (ANOVA), independent-sample t-test, or paired t-test; (3) Results: The development of the postoperative pain stages was recorded using the VAS score. Therefore, for Group A, the following results were obtained: the VAS at 6 h postoperatively showed an average value of 0.63 and a maximum value of 3. The results for Group B were the following: the VAS score at 6 h postoperatively showed an average value of 4.92, a maximum of 8, and a minimum of 2; (4) Conclusions: We can confirm that there are favorable statistical indicators regarding the postoperative pain management process during the first 24-38 h after a surgical intervention for breast cancer using local infiltration of anesthetics.

Overview of systematic reviews of Chinese herbal injections for sepsis

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing&gt;50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

Evaluation of markers of cerebral oxygenation and metabolism in patients undergoing clipping of cerebral aneurysm under total intravenous anesthesia versus inhalational anesthesia: A prospective randomized trial (COM-IVIN trial).

Anesthetic goals in patients undergoing clipping of cerebral aneurysm include maintenance of cerebral blood flow, oxygenation, and metabolism to avoid cerebral ischemia and maintenance of hemodynamic stability. We intend to study the influence of anesthetic agents on the outcome of aneurysmal subarachnoid hemorrhage (SAH). This is a prospective, randomized, parallel, single-center pilot trial approved by the Institutional Ethics Committee and is prospectively registered with the Clinical Trial Registry of India. Patients with aneurysmal SAH (aSAH) admitted to our institution for surgical clipping, fulfilling the trial inclusion criteria, will be randomized in a 1:1 allocation ratio utilizing a computerized random allocation sequence to receive either total intravenous anesthesia (n = 25) or inhalational anesthesia (n = 25). Our primary objective is to study the effects of these anesthetic techniques on cerebral oxygenation and metabolism in patients with aSAH. Our secondary objective is to evaluate the impact of these anesthetic techniques on the incidence of delayed cerebral ischemia and long-term patient outcomes in patients with aSAH. The Modified Rankin Score and Glasgow Outcome Scale (GOS) at discharge and 3 months following hospital discharge will be evaluated. An observer blinded to the study intervention will assess the outcome measures. This study will provide more insight as to which is the ideal anesthetic agent that offers a better neurophysiological profile regarding intraoperative cerebral oxygenation and metabolism, thereby contributing to better postoperative outcomes in aSAH patients.

Preliminary evidence of safety and effectiveness of Loxoprofen Sodium Cataplasm combined with physiotherapy for myofascial pain syndrome treatment: A randomized controlled pilot clinical trial.

Myofascial pain syndrome (MPS) is one of the most common causes of chronic skeletal muscle pain, which is closely related to skeletal muscle myofascial trigger point (MTRP). Since there is no first-line treatment for MPS, we investigated Loxoprofen Sodium Cataplasm combined with physiotherapy as a non-invasive therapy in patients at different levels to a protocol with superior efficacy that is safe and easy to promote. Moreover, this treatment could represent an alternative therapeutic strategy for low-income patients to a safer, more convenient, and more economical treatment scheme. A randomized clinical study was aimed at evaluating the safety and efficacy of Loxoprofen Sodium Cataplasm combined with physiotherapy in patients diagnosed with MPS in the pain clinic. We screened 100 patients with MPS, and using a computer-generated random allocation sequence, we stratified patients in a ratio of 2:1:1:1 (A: B: C: D) to one of the four treatment groups. Group A received Loxoprofen Sodium Cataplasm combined with extracorporeal shock wave therapy (ESWT) and transcutaneous electrical nerve stimulation (TENS). Group B received Loxoprofen Sodium Cataplasm alone. Group C received physiotherapy alone. Group D received Flurbiprofen Cataplasm combined with physiotherapy. After 2 weeks of treatment, the overall efficiency and secondary assessment indicators, including visual analog scale (VAS) scores, chronic soft tissue injury (CSTI) scores, Oswestry Disability Index (ODI) scores, or Northwick Park Neck Pain Questionnaire (NPQ) scores, were evaluated before and after treatment to analyze the difference in efficacy of each group. All groups were well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in overall efficiency (primary efficacy endpoint) (P = 0.0078) were observed in subjects of groups A and C. Showing valuable data of efficacy in primary and secondary endpoints, Loxoprofen Sodium Cataplasm combined with physiotherapy is superior in the treatment of MPS. https://www.chictr.org.cn/ (ChiCTR2100054756).

The effect of active oxygen-containing toothpaste on Streptococcus mutans and white spot lesions: An in-vivo randomized controlled trial

Fixed appliances limit patients' ability to clean their teeth, thus making orthodontic patients highly susceptible to developing white spot lesions (WSLs). Using patient compliance would be one of the simplest methods to prevent WSLs. A parallel trial design with 34 patients that met the eligibility criteria were randomized to experimental (received Blue M oxygen for health toothpaste) and control (received Colgate Total fluoridated toothpaste) groups. The eligibility criteria were that the patients should be aged 13-30 years, on fixed mechanotherapy, had undergone therapeutic extraction of all first premolars, had completed leveling and aligning, and had satisfactory oral hygiene (assessed using pretreatment and current Simplified Oral Hygiene Index scores). The objectives were to assess the effects of active oxygen-containing toothpaste on Streptococcus mutans (SM) and WSLs in patients undergoing fixed mechanotherapy. The random allocation sequence was generated using the RAND function in Microsoft Excel. The sequence generated was sealed in opaque white envelopes. The investigators and the participants were blinded until allocation. Blinding of the first author (J.A.G.) who dispensed the toothpaste or the participants was not possible. The outcome assessment was blinded by coding the plaque specimens sent for real-time polymerase chain reaction (RT-PCR) to ensure that the final data assessment was blinded. The study setting was the Department of Orthodontics and Dentofacial Orthopedics, Sri Ramachandra Institute of Higher Education and Research (SRIHER) University. The primary outcome was SM counts, which were analyzed using RT-PCR. The secondary outcome was WSL assessment, performed using DIAGNOdent and International Caries Detection and Assessment System (ICDAS) II criteria at baseline and after 4 weeks. The data were subjected to statistical analysis. Thirty-four patients were randomized to 17 per group and analyzed. RT-PCR showed lower SM in the experimental group (Ct= 32.25 ± 10.6) than in the control group (Ct= 30.9 ± 10.49). However, this was not statistically significant (P= 0.70). ICDAS scores remained the same from baseline and after 4 weeks for both groups. The DIAGNOdent values were in tandem with the ICDAS scores and showed minimal change for the 2 groups (P>0.05). A strong positive correlation was observed for DIAGNOdent and ICDAS scores (τb>0.30). No harms or adverse effects were observed or reported by the patients during the experimental period. The active oxygen-containing toothpaste showed a greater inhibitory effect on SM than the fluoridated toothpaste. However, this effect was minimal. Both kinds of toothpaste showed negligible effects on WSLs. Thus, active oxygen-containing toothpaste is as effective as fluoridated toothpaste. The Trial was registered in the Controlled Trials Registry India (CTRI/2021/10/037458). The full protocol can be obtained from any of the authors via e-mail. The project was self-funded.

Self-applied topical interventions for melasma: a systematic review and meta-analysis of data from randomized, investigator-blinded clinical trials.

Melasma is a common dermatological condition. Although its relevance as a skin condition is primarily of a cosmetic nature, it may affect the patient's wellbeing and quality of life. A broad range of treatment options is available, which makes it difficult to choose the most appropriate of those treatments. To summarize and critically appraise evidence from investigator-blinded randomized controlled trials (RCTs) on the efficacy and safety of self-applied topical interventions for melasma. We systematically searched MEDLINE and the Cochrane CENTRAL trials database for RCTs on topical, self-administered interventions for patients diagnosed with melasma. Eligibility was limited to RCTs that explicitly stated in their methods section (i) how they generated the random allocation sequence, and (ii) that the study outcome assessor was blinded to the participants' group allocation. Outcomes of interest included evaluator-assessed clinical scores (such as the Melasma Area and Severity Index), quality of life and patient-reported outcomes, as well as safety outcomes. The study findings were meta-analysed, pooling data from studies on the same comparisons, if this was possible. We assessed confidence in effect estimates using the GRADE approach. Our searches yielded 1078 hits. We included 36 studies reporting on 47 different comparisons of interventions. These included medical treatments such as 'triple combination cream' (TCC), over-the-counter cosmetic and herbal products, as well as sun creams covering different light spectra. Pooling data was possible for only two comparisons, topical tranexamic acid (TXA) vs. hydroquinone (HQ) and cysteamine vs. placebo. Direct comparisons were available for a variety of interventions; however, the reported outcomes varied greatly. Overall, our confidence in the effect estimates ranged from very low to high. Our findings indicate that TCC and its individual components HQ and tretinoin are effective in lightening melasma. Besides these established self-applied treatment options, we identified further medical treatments as well as promising cosmetic and herbal product treatment approaches. Furthermore, evidence suggests that using broad-spectrum sunscreen covering both the visible and ultraviolet-light spectrum enhances the treatment efficacy of HQ. However, with mostly small RCTs comparing treatments directly using a broad range of outcomes, further research is needed to draw conclusions about which treatment is most effective. What is already known about this topic? Melasma is a common dermatological disease. Although it is primarily a cosmetic condition, it can severely affect the patient's wellbeing and quality of life. Treatment options for melasma include a broad range of medical, cosmetic and herbal products. Given the large number of available interventions, it is difficult for clinicians and for patients to make informed decisions about which treatment to choose. What does this study add? We systematically assessed data from investigator-blinded randomized controlled trials of self-applied topical interventions. Our GRADE evaluations of confidence in the findings ranged from very low to high and may help clinicians and patients navigate treatment decisions. Besides the established self-applied medical treatment options, we identified promising cosmetic and herbal treatment approaches. Evidence suggests sunscreen covering the ultraviolet (UV)- and visible light spectra increases treatment efficacy compared with UV-only protection.

Patient-centered mobile tuberculosis treatment support tools (TB-TSTs) to improve treatment adherence: A pilot randomized controlled trial exploring feasibility, acceptability and refinement needs

Digital adherence technologies hold promise to improve patient-centered tuberculosis (TB) monitoring, yet few studies have incorporated direct adherence monitoring or assessed patients' experiences with these technologies. We explored acceptability, feasibility, and refinement needs of the TB Treatment Support Tools (TB-TSTs) intervention linking a mobile app, a urine drug metabolite test, and interactive communication with a treatment supporter. This pilot study was a parallel-designed single-center randomized controlled trial with exit interviews. Newly diagnosed TB patients were randomized 1:1 using a treatment allocation button in the REDCap software preloaded with a random allocation sequence to usual care or usual care plus the TB-TSTs intervention from a respiratory medicine hospital in the province of Buenos Aires, Argentina and followed for 6-months. Due to the nature of the intervention, blinding to the group allocation could not be achieved for the recruiter or patients. The treatment outcome data extractor was blinded to the group allocation of the participants. Intervention participants used the app to report self-administering medication, potential side effects, submit photos of the urine test, and interact with a treatment supporter. Outcomes were feasibility, acceptability, and treatment outcomes. Forty-two patients were enrolled and evenly assigned to each group. Intervention participants submitted 147·2±58 (mean, SD) medication self-administration and 144·5±55 side effect reports out of 180 and 47.5±38·4 photos of the urine test out of 77. Treatment success for usual care was 81% [17/21] and 95% [20/21] for the TB-TSTs intervention. Thirty-three themes were identified within the main categories of motivation, what worked, issues experienced, and recommendations. Participants (n=12) rated it as 'easy to use' (4.57/5), 'would highly recommend to others' (4·43/5) and reported that access to the treatment support was a critical component. Recommendations included adding an alarm, appointment reminders, and off-line functionality. Findings suggest that the TB-TSTs intervention was feasible and acceptable and further refinement and testing is warranted. National Institute of Health K23NR017210.

Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial

PCR-based testing has transformed the management of suspected respiratory viral infections. We aimed to determine whether multiplex bacterial PCR of bronchoalveolar lavage fluid aids antibiotic stewardship in patients with pneumonia. This investigator-initiated, multicentre, randomised controlled trial was conducted at two tertiary care centres in Switzerland (University Hospital of Basel and Kantonsspital St Gallen). Patients aged 18 years or older who were admitted to hospital with suspected pneumonia, had a clinical indication for bronchoscopy with bronchoalveolar lavage, and were at risk of Gram-negative bacterial infection were included. Patients were randomly assigned (1:1) to either the multiplex bacterial PCR group or the conventional microbiology control group using a random allocation sequence. Treating physicians were not masked, but the committee panel was masked to patient randomisation. All patients underwent bronchoscopy with bronchoalveolar lavage and samples were assessed by conventional microbiological culture (and additionally, in the PCR group, by multiplex bacterial PCR for Gram-negative rods using the Unyvero Hospitalized Pneumonia [HPN] Cartridge; Curetis, Holzgerlingen, Germany). Patients received empirical antibiotic therapy as clinically indicated by the treating physician. In the PCR group, a recommendation regarding antibiotic therapy was made approximately 5 h after taking the sample. The primary outcome was the time in hours on inappropriate antibiotic therapy from bronchoscopy to discharge or to 30 days after bronchoscopy. This trial was registered with the International Clinical Trials Registry Platform, ISRCTN95828556. Between May 31, 2017, and Sept 25, 2019, 740 patients with pneumonia were screened for eligibility and 208 were included and randomly assigned to the PCR group (n=100) or conventional microbiology control group (n=108). The mean age of patients was 65·9 years (SD 14·0) and 135 (65%) were male. After daily follow-up until hospital discharge or for a maximum of 30 days, the duration of inappropriate antibiotic treatment was significantly shorter by 38·6 h (95% CI 19·5-57·7) in the PCR group than in the control group (adjusted mean 47·1 h [34·7-59·5] vs 85·7 h [78·8-95·6]; p<0·0001), which translates as a decrease in the duration of inappropriate antibiotic therapy of 45·0% (37·9-52·1). Adverse events due to antimicrobial therapy occurred in nine patients (five [5%] in the PCR group vs four [4%] in the control group) and due to bronchoscopy occurred in four patients (two [1%] vs two [1%]). There were eight (8%) deaths in the PCR group and 11 (10%) in the control group. All in-hospital deaths were attributed to a respiratory cause. Multiplex bacterial PCR examination of bronchoalveolar lavage decreases the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and at risk of Gram-negative rod infection. This approach warrants further consideration in future antibiotic stewardship strategies. Curetis and the Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland.

Primer of Epidemiology IV. Study designs II: Interventional or experimental designs.

In this article, we describe experimental study designs and focus on randomized controlled trials. Experimental studies are intervention studies in which the investigator tests a new treatment on a selected group of patients. In a controlled design, the effects of an intervention (new treatment) are measured by comparing the outcome in the experimental group with that in a control group. Experimental studies are similar to cohort studies except that the exposure is a deliberate change (intervention) made by the researcher in one group of participants and it overcomes confounding because the treatment is assigned randomly. Further, we discuss various types of randomization (random sequence allocation) and importance of allocation concealment and blinding for proper assessment of outcomes in randomized trials.

Knowledge of evidence-based research methodology amongst orthodontic postgraduate residents in four universities: An international survey

The aim of this international survey was to assess knowledge concerning the design, conduct, critical appraisal and synthesis of clinical studies among senior orthodontic postgraduate residents. Senior postgraduate residents from four universities in Europe and the United States were invited to complete a custom questionnaire. The overall correct answer score and proportion of residents correctly answering each of the 10 questions within the survey were analysed with descriptive statistics, analysis-of-variance, chi-squares test and linear regression at 5%. A total of 46 residents with mean age of 30.4 years scored an overall % correct score of 48.8%±13.8%, with the % of correct answers to each question ranging from 7 to 89%. The worst-answered questions pertained to correctly characterizing sensitivity and specificity (7%), number needed to treat (9%), credibility of trial synthesis in meta-analysis (35%) and publication bias (37%). The vast majority of postgraduate students could correctly identify entities that can be blinded in a randomized trial (89%), statistical power of a trial (74%) and proper methods for random allocation sequence (67%). No statistically significant differences were found among the four included universities, while residents having obtained another degree apart from dentistry scored better than others (+9.5%; 95% confidence interval: 0.6% to 18.5%; P=0.04). Postgraduate residents in orthodontics possessed moderate knowledge on evidence-based methodology. Efforts should be reinforced to assimilate research methodology perspectives in the postgraduate curricula of universities, in order to further augment critical training of orthodontic specialists.

Monday-focused tailored rapid interactive mobile messaging for weight management 2 (MTRIMM2): results from a randomized controlled trial.

Text-messaging interventions can reach many individuals across a range of socioeconomic groups, at a low cost. Few randomized controlled trials (RCTs) of text-messaging weight loss interventions have been conducted in United States. From September of 2016 to September of 2018, we conducted a two-parallel group, superiority, RCT of a 16-week text-messaging, weight loss intervention in Baltimore, Maryland, in overweight and obese adults younger than 71, who were able to receive text-messages. Our objective was to assess the effect of receiving the message content only (in printed documents distributed at baseline and week 8), versus receiving messages via short messaging service (SMS) on weight loss (primary outcome), body mass index, perceived exercise benefits and barriers, self-efficacy, and physical activity (PA). The random allocation sequence was equally balanced intervention groups by gender and age groups. Participants were randomized after the baseline assessment. Then, participants and most study staff were unblinded. Follow-up assessments were conducted at 8-, 16-, and 42-week post randomization. We performed intention-to-treat analysis using mixed linear regression models. Of the 155 adults randomized (printed messages =77, SMS =78), 87.1% were women, 53.5% were African Americans, and 93.5% non-Hispanic. Participants who completed at least one follow-up assessment were included in regression analyses (n=145, printed messages =74, SMS =71). Compared to baseline, at the 42-week assessment, the average percent weight loss was 1.23 for the SMS group (P=0.006) and 0.86 for the printed messages group (P=0.047). Both groups experienced small reductions in weight (printed messages: -0.96 kg, P=0.022; SMS: -1.19 kg, P=0.006), BMI (printed messages: -0.32, P=0.035; SMS: -0.52, P=0.002), and percent energy from fat consumption (printed messages: -1.43, P=0.021; SMS: -2.14, P≤0.001). No statistically significant between groups differences were detected for any of the study outcomes. SMS response rates were not statistically significantly associated with study outcomes. No adverse events were reported. A semi-tailored SMS weight loss intervention among overweight and obese adults was not statistically superior in efficacy to paper-based messaging. ClinicalTrials.gov Identifier: NCT04506996.

What you read is what you get: Are orthodontic randomized clinical trials correctly titled?

Because of their importance in health care research, randomized controlled trials (RCTs) should be correctly labeled in the title to ensure it reflects the methodologic standards undertaken. This study aimed to assess whether orthodontic RCTs are correctly titled RCTs, and trial characteristics that influence correct labeling in titles were explored. Orthodontic RCTs published between January 1, 2015 and September 30, 2020 in 7 orthodontic journals were identified. For a trial to be considered an RCT, random allocation sequence generation and allocation concealment mechanisms should be reported in the study methodology. Trial characteristics at the RCT level were extracted, and frequency distributions were calculated for the included trial characteristics. A 2-stage continuation ratio ordinal logistic regression model was used to assess associations between the dependent variable (non-RCT, unclear, RCT) and the trial characteristics. One-hundred and seventy-three RCTs were analyzed. Of these, 112 (64.7%) were assessed as true RCTs, with 109 (64.1%) correctly labeled as RCTs. The American Journal of Orthodontics and Dentofacial Orthopedics (AJODO) published the most trials that were correctly labeled as RCTs (90.5%). In the adjusted model, the type of journal influenced the correct labeling, with all journals compared with AJODO having lower odds of correct RCT classification. Multicenter trials were associated with higher odds of being correctly labeled as an RCT. Compared with previous investigations, the correct labeling of orthodontic RCTs in the title of the report has improved substantially. The type of journal and multicenter trials influenced the correct labeling of a trial as an RCT. The number and odds of RCTs being correctly labeled as RCTs were higher in trials published in AJODO.