Animal Model for Glucocorticoid Induced Osteoporosis: A Systematic Review from 2011 to 2021

Clinical and experimental data have shown that prolonged exposure to GCs leads to bone loss and increases fracture risk. Special attention has been given to existing emerging drugs that can prevent and treat glucocorticoid-induced osteoporosis GIOP. However, there is no consensus about the most relevant animal model treatments on GIOP. In this systematic review, we aimed to examine animal models of GIOP centering on study design, drug dose, timing and size of the experimental groups, allocation concealment, and outcome measures. The present review was written according to the PRISMA 2020 statement. Literature searches were performed in the PubMed electronic database via Mesh with the publication date set between April, 2011, and February 2021. A total of 284 full-text articles were screened and 53 were analyzed. The most common animal species used to model GIOP were rats (66%) and mice (32%). In mice studies, males (58%) were preferred and genetically modified animals accounted for 28%. Our work calls for a standardization of the establishment of the GIOP animal model with better precision for model selection. A described reporting design, conduction, and selection of outcome measures are recommended.

Trends in Clinical Trial Registration in Dentistry: An Analysis of Registered Clinical Trials in the Clinical Research Information Service from 2013 to 2021 in South Korea

The Clinical Research Information Service (CRIS) in South Korea provides a clinical trial registry platform in which all clinical trials should be mandatorily and prospectively registered. However, to date, the registration status of clinical trials in the field of dentistry has not been investigated. Therefore, this study aimed to provide an overview of the methodological design and trends of the registered clinical trials over a period of nine years. Information about registered clinical trials in the field of dentistry from the CRIS was comprehensively collected from 2013 to 2021. The details assessed from the collected trials include: type of sponsors, recruitment status, study design, randomization, allocation concealment, single or multi-centric, retrospective or prospective registration, and publication status. A total of 65 registered clinical trials were identified. The number of clinical trials in dentistry in South Korea was found to be less; however, an increasing trend was observed in the recent three years. A majority of the trials were interventional (81.5%), single-centered (86.2%), and conducted on patients (81.5%) and in private hospitals (55.4%). A considerable number of trials had an unclear phase, were retrospectively registered, and rarely published. Regarding the quality, most trials have inadequately reported the method of randomization and allocation concealment. The number of clinical trials in dentistry is still low in South Korea, and most of them were registered retrospectively. A poor-quality reporting of methods at several specific areas was observed. It is necessary for dental investigators to raise awareness of the need to register clinical trials.

Randomized Controlled Trials

A randomized controlled trial (RCT) is a prospective, comparative, quantitative experiment/study that is performed under controlled conditions with random allocation of interventions to comparison groups. Among all the clinical study designs, evidence generated from RCTs is considered to be at top of the evidence pyramid. There are many different RCT designs and they can be classified on the basis of interventions evaluated, participants’ exposure and level of blinding. All RCTs should be planned prospectively, a research question should be formulated, sample population approached and informed consent obtained from participants of the trial. These consented subjects are randomly assigned to any of the study arms and the changes are then measured over time. The basic principles to designing an RCT include formulating a research question, developing a protocol, randomization, allocation concealment, blinding, sample size calculation and registering of RCTs. Appropriate guidelines for reporting RCTs should be followed and RCTs should only be conducted if they are ethically viable, economical and clinically worthwhile. Keywords: Randomised Control Trial (RCT)

Comparison of mean canine retraction between healed and recently extracted site: A single center, randomized control trial

Objectives: The objective of this “2-arm parallel” trial was to compare mean canine retraction into healed and recently extracted site. Materials and Methods: One of the sides of the maxillary dental arch of the patients having undergone orthodontic treatment at orthodontic department of a private hospital was randomly allocated to recent extraction side, while the contra-lateral side to healed extraction site. Eligibility criteria included no active local or systemic diseases including long-term medications. The main outcome was canine retraction into the extraction sites. Simple randomization technique was used allocate the right and left sides of the arch to one of the groups with allocation concealment through sequentially numbered, opaque, and sealed envelopes. Blinding was applicable for outcome assessor only. The patients were reviewed after 1 month of retraction. Data were analyzed on an intention to treat basis, using paired t-test was applied to compare the canine retraction between healed and recently extracted site (P ≤ 0.05 statistically significant). Results: Thirty-five patients with a mean age of 17.6 years were randomized in a 1:1 ratio for one of the sides of the arch to either recent extraction site or healed extraction site. After a month active retraction in 32 patients, the canine at recent extraction site moved 1.17 ± 0.27 mm in 1 month and 0.75 ± 0.26 mm in 1 month on the healed extraction site (P = 0.00). Two patients were lost to follow-up. No harm was observed. Conclusion: The results of the study indicate that the mean canine retraction was faster into the recent extraction site. The mean difference of 0.45 mm between the two sides was found be statistically significant.

Association of study design features and treatment effects in trials of chronic medical conditions: a meta-epidemiological study

ObjectivesTo evaluate the association of study design features and treatment effects in randomised controlled trials (RCTs) evaluating therapies for individuals with chronic medical conditions.DesignMeta-epidemiological study.SettingRCTs from meta-analyses published in the 10 general medical journals with the highest impact factor published between 1 January 2007 and 10 June 2019 and evaluated a drug, procedure or device treatment of chronic medical conditions.Main outcome measuresThe association between trial design features and the effect size, reporting a ratio of ORs (ROR) and 95% confidence interval (CI).ResultsWe included 1098 trials from 86 meta-analyses. The most common outcome in the trials was mortality (52%), followed by disease progression (16%) and adverse events (12%). Lack of blinding of patients and study personnel was associated with a larger treatment effect (ROR 1.12; 95% CI 1.00 to 1.25). There was no statistically significant association with random sequence generation, allocation concealment, blinding of outcome assessors, incomplete outcome data, whether trials were stopped early, study funding, type of interventions or with type of outcomes (objective vs subjective).ConclusionThe meta-epidemiological study did not demonstrate a clear pattern of association between risk of bias indicators and treatment effects in RCTs in chronic medical conditions. The unpredictability of the direction of bias emphasises the need to make every attempt to adhere to blinding, allocation concealment and reduce attrition bias.Trial registration numberNot applicable.

Validation of a Musculoskeletal Digital Assessment Routing Tool (DART): Protocol for a Pilot Randomised Crossover Non-Inferiority Trial (Preprint)

BACKGROUND Musculoskeletal conditions account for 16% of global disability, resulting in a negative effect on millions of patients and an increasing burden on healthcare utilization. Digital technologies to improve health care outcomes and efficiency are considered a priority; however, innovations are rarely tested with sufficient rigor in clinical trials, the gold standard for clinical proof of safety and efficacy. We have developed a new musculoskeletal Digital Assessment Routing Tool (DART) that allows users to self-assess and be directed to the right care. DART requires validation in a real-world setting prior to implementation. OBJECTIVE This pilot study will assess the feasibility of a future trial by exploring key aspects of trial methodology, assess the procedures and collect exploratory data to inform the design of a definitive, randomized, crossover, non-inferiority trial to assess DART safety and effectiveness. METHODS We will collect data from 76 adult participants presenting to an NHS England GP practice with a musculoskeletal condition. Participants will complete both a DART assessment and a physiotherapist-led triage with the order determined by randomization. The primary analysis will involve an absolute agreement ICC (A,1) estimate with 95% confidence intervals between DART and the clinician for assessment outcomes sign-posting to condition management pathways. Data will be collected to allow analysis of participant recruitment and retention, randomization, allocation concealment, blinding, data collection process and bias. In addition, the impact of trial burden and potential barriers to intervention delivery will be considered. DART user satisfaction will be measured using the System Usability Scale. RESULTS A UK NHS ethics submission will be submitted during June 2021 and pending approval, recruitment will commence during August 2021 with data collection anticipated to last for 3 months. Results will be reported in a follow-up paper later in 2021. CONCLUSIONS This study will inform the design of a randomized controlled crossover non-inferiority study that will provide evidence concerning mHealth DART system clinical sign posting in an NHS setting prior to real-world implementation. Success should produce evidence of a safe, effective system with excellent usability, facilitating quicker and easier patient access to appropriate care while reducing the burden on primary and secondary care musculoskeletal services. This rigorous approach to mHealth system testing could be used as a guide for other developers of similar applications. CLINICALTRIAL This trial is registered with Clinical Trials number NCT04904029

The Gingiva from the Tissue Surrounding the Bone to the Tissue Regenerating the Bone: A Systematic Review of the Osteogenic Capacity of Gingival Mesenchymal Stem Cells in Preclinical Studies

The current review aims to systematically assess the osteogenic capacity of gingiva-derived mesenchymal stem cells (GMSCs) in preclinical studies. A comprehensive electronic search of PubMed, Embase, Web of Science, and Scopus databases, as well as a manual search of relevant references, was performed in June 2020 without date or language restrictions. Eligibility criteria were the following: studies that compared mesenchymal stem cells (MSCs) derived from the gingiva with other MSC sources (in vitro or in vivo) or cell-free scaffold (in vivo) and studies that reported at least one of the following outcomes: osteogenic potential and new bone formation for in vitro and in vivo, respectively. Moreover, the assessment of included studies was conducted using appropriate guidelines. From 646 initial retrieved studies, 35 full-text articles were subjected to further screening and 26 studies were selected (20 in vitro studies and 6 in vivo studies). GMSCs showed great proliferation capacity and expressed recognized mesenchymal stem cell markers, particularly CD90. In vitro, MSC sources including GMSCs were capable of undergoing osteogenic differentiation with less ability in GMSCs, while most in vivo studies confirmed the capacity of GMSCs to regenerate bony defects. Concerning the assessment of methodological quality, in vitro studies met the relevant guideline except in five areas: the sample size calculation, randomization, allocation concealment, implementation, and blinding, and in vivo publications had probably low risk of bias in most domains except in three areas: allocation concealment, attrition, and blinding items.

Intervention for Married Immigrant Women in Korea: A Systematic Review

Purpose: This study aimed to review the intervention programs designed for married immigrant women living in Korea.Methods: A total of 39 articles published from 2010 to 2020 were selected and analyzed using domestic and international web-based academic databases according to a systematic literature review procedure. The selected studies were evaluated for quality according to RoB (Risk of Bias) and RoBANS (Risk of Bias for Non-randomized studies). Additionally, intervention programs and outcome variables were based on the Nursing Intervention Classification (NIC) and Nursing Outcome Classification (NOC) system.Results: According to the NIC categories, 69.2% of the interventions were in the behavioral domain, and 23.1% were in the family domain. The outcome variables primarily measured in NOC categories were psychological well-being (45.8%), health knowledge (11.0%), and health belief (10.2%). The quality of the selected studies was low overall in random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome data in randomized controlled trials (RCT) studies and confounding variables, blinding of outcome data, and incomplete outcome bias in non-RCT studies.Conclusion: Based on the results of this study, future studies will have to consider the characteristics of the subjects, life cycle, daily life, or language limitations. In addition, it is necessary to develop high-quality programs through continuous research on currently and frequently used interventions and outcome variables and on other various mediations and to verify the outcome variables.

Comparison of micro skin grafting and transplantation of non-cultured melanocyte keratinocyte suspension for the treatment of stable vitiligo: A pilot study

Objectives: We conducted this pilot study to compare the outcomes of non-cultured epidermal suspension (NCES) with that of micro skin grafting (MSG) in the treatment of stable vitiligo Material and Methods: Twenty-nine patients with clinically stable vitiligo lesions (defined as the occurrence of no new lesions and no increase in the size of preexisting lesions for the past six months) and age group between 12 and 70 years were enrolled in the study. The enrolled patients were randomized into two groups using simple randomization using computer-generated random numbers, and allocation concealment was done using opaque sealed envelopes. Group 1 was comprised of 15 patients with 23 stable vitiligo lesions, and group 2 comprised of 14 patients with 22 stable vitiligo lesions. Patients in group 1 were transplanted with non-cultured melanocytes and keratinocytes. Patients in group 2 were treated using micro skin grafts after obtaining written informed consent. Ethical clearance was obtained from the Institute ethics committee, and the principles of the 1975 Declaration of Helsinki were followed. Results: At the end of four months post-treatment, two patients (one in each group) did not follow up after removal of dressing at the first week. Results were analyzed at four months in 27 patients – 14 patients with 22 lesions in group 1 and 13 patients with 21 lesions in group 2. Repigmentation at 16 weeks post-surgery was evaluated. Excellent repigmentation (>90%) was seen in 45.45% of lesions in the non-cultured epidermal suspension (NCES) group as compared to 38.09% of lesions in the micro skin grafting (MSG) group, and this difference was not statistically significant (p = 0.7597). Repigmentation > 75% was achieved in 54.54% of lesions in the non-cultured epidermal suspension (NCES) group compared to 38.09% of lesions in the micro skin grafting (MSG) group, and this difference was not statistically significant (p = 0.3640). Both the groups did not have any significant complications like scarring, milia, or any cobble stoning at the donor site. The recipient area had resistance to the spread of pigment at the margins of lesions. Six lesions in both the groups with excellent response, 3 in each group had achromic fissure or hypopigmented halos at the margins of lesions. Conclusion: Both non-cultured epidermal suspension (NCES) and micro skin grafting (MSG) have been found to be safe and effective modalities with comparable efficacy in the surgical treatment of stable vitiligo. However, future trials on large sample sizes are warranted to validate our results.

The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement

Many randomized controlled trials (RCTs) are biased and difficult to reproduce due to methodological flaws and poor reporting. There is increasing attention for responsible research practices and implementation of reporting guidelines, but whether these efforts have improved the methodological quality of RCTs (e.g., lower risk of bias) is unknown. We, therefore, mapped risk-of-bias trends over time in RCT publications in relation to journal and author characteristics. Meta-information of 176,620 RCTs published between 1966 and 2018 was extracted. The risk-of-bias probability (random sequence generation, allocation concealment, blinding of patients/personnel, and blinding of outcome assessment) was assessed using a risk-of-bias machine learning tool. This tool was simultaneously validated using 63,327 human risk-of-bias assessments obtained from 17,394 RCTs evaluated in the Cochrane Database of Systematic Reviews (CDSR). Moreover, RCT registration and CONSORT Statement reporting were assessed using automated searches. Publication characteristics included the number of authors, journal impact factor (JIF), and medical discipline. The annual number of published RCTs substantially increased over 4 decades, accompanied by increases in authors (5.2 to 7.8) and institutions (2.9 to 4.8). The risk of bias remained present in most RCTs but decreased over time for allocation concealment (63% to 51%), random sequence generation (57% to 36%), and blinding of outcome assessment (58% to 52%). Trial registration (37% to 47%) and the use of the CONSORT Statement (1% to 20%) also rapidly increased. In journals with a higher impact factor (>10), the risk of bias was consistently lower with higher levels of RCT registration and the use of the CONSORT Statement. Automated risk-of-bias predictions had accuracies above 70% for allocation concealment (70.7%), random sequence generation (72.1%), and blinding of patients/personnel (79.8%), but not for blinding of outcome assessment (62.7%). In conclusion, the likelihood of bias in RCTs has generally decreased over the last decades. This optimistic trend may be driven by increased knowledge augmented by mandatory trial registration and more stringent reporting guidelines and journal requirements. Nevertheless, relatively high probabilities of bias remain, particularly in journals with lower impact factors. This emphasizes that further improvement of RCT registration, conduct, and reporting is still urgently needed.