Efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular disease : a meta-analysis of randomized controlled trials

명승권 서울대학교 대학원 2013 국내박사

Introduction Randomized controlled trials have reported inconsistent findings regarding the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. The current study aimed to investigate the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases by using a meta-analysis of randomized controlled trials. Methods We searched PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov in June and additionally November 2012. Two of the authors independently reviewed and selected eligible randomized controlled trials, based on pre-determined selection criteria. A meta-analysis of randomized controlled trials was performed. Results Out of 2,240 articles retrieved from databases and relevant bibliographies, a total of 50 RCTs, which involved 294,478 participants (156,663 intervention and 137,815 control groups), were included in the final analyses. In a fixed-effect meta-analysis of 50 RCTs, supplementation with vitamins and antioxidants did not reduce the risk of major cardiovascular events (relative risk [RR], 1.00; 95% confidence interval [CI], 0.98-1.02; I2 = 41.6%). Overall, no beneficial effect of those supplements was observed in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, supply source for supplement, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation marginally increased the risk of angina pectoris, while low-dose vitamin B6 supplementation slightly decreased the risk of major cardiovascular events. However, in the subgroup meta-analysis of high-quality RCTs within each category, those beneficial or harmful effects disappeared. Also, even though vitamin B6 supplementation decreased the risk of cardiovascular death in high-quality trials, and vitamin E supplementation decreased the risk of myocardial infarction, those beneficial effects were only shown in RCTs supplied with supplements by pharmaceutical industry. Conclusion Our meta-analysis found that there is no evidence to support the use of vitamin and antioxidant supplements in the prevention of cardiovascular diseases.

Bayesian Methods for the Incorporation of Real World Data into the Design and Analysis of Randomized Controlled Trials

Haine, Lillian M. F University of Minnesota ProQuest Dissertations & T 2023 해외박사(DDOD)

Randomized controlled trials (RCTs) are considered the most rigorous form of clinical evidence for regulatory decision making and are the gold-standard for studying causal relationships. Though RCTs have benefits, they also have some drawbacks. One major criticism of RCTs is that they are inefficient, requiring substantial and steadily increasing costs in both time and money. One way to increase efficiency of RCTs would be to leverage external data on one or both trial arms in the design or analysis of the RCT. Though RCTs do not traditionally leverage external data, there are often multiple sources of external data that could be leveraged to improve the efficiency of a RCT, such as previously conducted early phase clinical trials, concurrently conducted observational studies, electronic health records, medicare claims data, and other real world data (RWD) sources. Incorporating these data could lead to desirable properties, such as increasing precision, decreasing necessary sample size, and reducing costs, but this must be done rigorously to avoid undermining the advantages of RCTs. In this dissertation we investigate Bayesian approaches to incorporating external data into the design and analysis of randomized controlled trials. We aim to improve trial efficiency by decreasing necessary trial sample size, improving trial power, alongside improving statistical precision of secondary trial analyses that often are underpowered. In Chapter 2, we introduce a Bayesian approach for incorporating observational data into the analysis of a clinical trial through a Semi-Supervised Mixture distribution and Multisource Exchangeability Model (SS-MIX-MEM). We then apply the SS-MIX-MEM to the context of binary outcomes, when many of the same baseline covariates are measured between the RCT and the observational study, and there is no missingness through an analysis of the INSIGHT FLU-IVIG trial and illustrate how we can gain efficiency by incorporating the data from INSIGHT FLU 003 via the SS-MIX-MEM approach. In Chapter 3, we introduce a trial design that facilitates borrowing during an interim futility analysis using the SS-MIX-MEM approach. We also find the optimal stopping point for this trial design, which aims to leverage external data to improve trial efficiency by stopping ineffective treatments earlier, with fewer trial participants without inflating type 1 error as we only allow early stopping and borrowing in an interim futility analysis. In Chapter 4, we apply the SS-MIX-MEM approach to a secondary analysis of a recently conducted randomized controlled trial, COVID-OUT, borrowing from external N3C data to increase effective trial sample size and power. This analysis focuses on the secondary composite endpoint of emergency department visits and hospitalizations for Covid-19, and all-cause mortality through 28 days, which is a clinically important endpoint to guidelines committees and regulators. In summary, incorporating external RWD into the design and analysis of randomized controlled trials is a promising and exciting area of research that could potentially allow us to leverage the complementary strengths of RWD and RCT data to move clinical research forward.

Innovative Randomized Controlled Trial Design and Analysis Methods to Account for and Examine Variations in Population Health in Low and Middle-Income Countries

Butzin-Dozier, Zachary ProQuest Dissertations & Theses University of Cali 2022 해외박사(DDOD)

Reliance on traditional research methods in situations where innovative methodologies are superior can hinder inference. In global health research, where wasted resources can be equated with lives lost, non-adaptation of promising methods has dire consequences. Given the high cost of randomized controlled trials (RCTs), one major obstacle in these studies is the Type II error, in which an investigator fails to reject the null hypothesis when the null hypothesis is false. Unexpected disease transmission rates may lead studies to be underpowered and yield Type II errors. Furthermore, even if an RCT correctly rejects or fails to reject the null, data may not be fully utilized if investigators only analyze and report the intervention effect in the total study sample. Only focusing on quantifying the overall impact of the intervention of interest may neglect investigation into important observational relationships between covariates of interest or heterogeneity of the intervention effect in population subgroups, although these observational analyses and subgroups of interest should be pre-specified to maintain transparency and replicability. As participants were not randomized to receive exposures represented by covariate values, additional analytic rigor and inferential caution must be exercised in order to enable meaningful interpretation. My dissertation aims to explore three examples of potential methodological solutions to these challenges to inference in RCTs: a systematic review of the ring trial design, a targeted learning analysis of treatment heterogeneity, and an observational analysis of multiple biomarkers using trial data. Chapter 1. Spatiotemporal clustering: ring trials. For cluster RCTs in emergent and elimination disease settings, unpredictable spatiotemporal clustering often leads to imbalanced clusters, or even clusters with zero incident cases, which can reduce study power and limit inference. Ring trials, a trial design in which the units of randomization are responsively-defined clusters of individuals in social or physical proximity to an index case, may improve investigators’ ability to make inferences in these settings. Despite this potential utility, this RCT design remains under-examined and under-utilized. Investigators conducted a systematic review of the ring trial design to examine the existing applications of this study design as well as its benefits and drawbacks. We identified 26 ring trials, 15 cluster-randomized trials that used ring interventions, five trials that used ring recruitment and randomized within rings, and one individually-randomized trial that used a ring intervention. Ring trial designs require strong disease surveillance and contact tracing mechanisms, rapid intervention delivery systems, and a treatment with a strong post-exposure prophylactic effect. In these settings, ring trials can retain power despite unpredictable spatiotemporal clustering of the outcome of interest.Chapter 2. Heterogeneity in treatment effect: targeted learning analysis of treatment heterogeneity. Even if there is an effect of the intervention on the outcome among certain individuals, a study may fail to detect this relationship if the effect is heterogeneous in the study sample. Investigators can gain additional insight through analysis of the conditional average treatment effect, which is the treatment effect based on individual covariate status. Using data from the WASH Benefits study, which enrolled pregnant mothers and young children in rural Bangladesh, analysis of treatment heterogeneity can improve our understanding of child growth in low and middle-income countries. Despite the widespread use of water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions, investigators have found mixed evidence regarding these interventions’ impact on child growth and development. Insufficient reduction of pathogens may explain WSH’s lack of impact, and environmental enteric dysfunction (EED), a condition of impaired intestinal permeability and inflammation, may modify the impact of WSH and N interventions on child growth. This study applied targeted machine learning methods to assess treatment heterogeneity of N+WSH, WSH, and N interventions on child growth by pathogen and EED biomarker status. We found that children with greater levels of myeloperoxidase, a gut inflammation biomarker associated with EED, and Campylobacter, a genus of bacteria that is associated with EED onset, had a greater effect of all treatments on growth. These results contribute to the body of literature characterizing individual predictors of N+WSH, WSH, and N intervention effectiveness as well as our understanding of EED.Chapter 3. Maximizing data utilization: observational analysis of high-dimensional data nested within a randomized controlled trial. Trials devote enormous resources to evaluating the effect of the randomized intervention in the study sample, but limiting analyses to only include this intervention may neglect the wealth of data that these RCTs can provide. In addition to analysis of the effect of the intervention, investigators can conduct observational analyses nested within an RCT, although these analyses will require additional methodological rigor in order to limit confounding and bias to enable meaningful inference. Data from the WASH Benefits study provide an opportunity to assess the relationship between stress neurobiology, an exposure that could not be ethically randomized, and child development. Stress has been implicated as a key pathway by which adverse circumstances can lead to developmental impairment, and prior studies have indicated a possible link between stress and subsequent development. This study evaluated the relationship between stress and development through an observational analysis nested within an RCT. We assessed physiologic measures of stress using measures of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) system, and oxidative status. We constructed generalized additive models to compare development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders. We found that measures of HPA axis activity were associated with poor development outcomes. These observations support the use of HPA axis biomarkers, particularly cortisol and glucocorticoid receptor methylation, to indicate children who are at risk of poor developmental outcomes.This study explores and provides applied examples of RCT design and analysis methods that may improve efficiency in global epidemiologic research. This research serves to 1) improve our understanding of a neglected trial design and explore innovative methods of analyzing trial data; 2) identify which characteristics define amenability to N+WSH, WSH, and N interventions, providing insights that EED may be associated with treatment effectiveness; 3) evaluate the relationship between stress biomarkers and child development through observational analyses nested within an RCT, which supports the use of HPA axis biomarkers to indicate children at risk for poor developmental outcomes.

Effects of electroacupuncture for knee osteoarthritis : a systematic review and meta-analysis

심재우 경희대학교 대학원 2016 국내석사

국내 Randomized controlled trial(RCT) 관련 침 논문의 평가와 발전 모색을 위한 국내 및 국제 학술지 비교 연구

鄭載澈 동국대학교 2008 국내석사

Objective : To improve the methodological quality of Korean acupuncture trials comparing randomized controlled trials(RCTs) published in Korean Journal with RCTs published in international journals. Methods : Searches were performed in May, 2007 for acupuncture studies using Pubmed and The Journal of Korean Acupuncture and Moxibustion society. Search terms used was 'acupuncture'. Included trials were 11 Korean trials and 4 international trials. The author extracted data concerning study methods and quality according to STRICTA. Results : Most of included trials in Korean didn't reported details about practitioner background, control interventions, randomization methods, patient blind, assessor blind, drop-out description, procedure of receiving informed consents and ethical approval compared with trials published in international journals. Conclusion : This study shows that it is needed to report clearly the methodological part according to STRICTA, modified Jadad scale and ethics approval procedures for improving the methodological quality of Korean acupuncture trials.

Quantifying the Extendibility of Inferences From Randomized Controlled Trials to Target Populations

Farmer, Alyssa The Ohio State University ProQuest Dissertations & 2023 해외박사(DDOD)

Randomized controlled trials (RCTs) typically aim to identify a causal effect of a treatment on an outcome. Due to voluntary participation and exclusion criteria, inferences made from RCTs typically only naturally apply to populations similar to trial participants. As a result, researchers have proposed methods to extend treatment effect estimates to broader target populations. The extent to which inferences from a trial can be reliably extended to a population depends on factors such as sample size, level of treatment effect heterogeneity, and similarity of the covariate distributions between the trial and the population. Several metrics have been developed to describe the extendibility of inferences to a target population, but leading metrics have limitations such as failing to consider the relationship between the covariates and the outcome.The main aspect of our work is on the development of a new extendibility metric, the Extendibility Index (EI). The EI has three main advantages: (1) it incorporates outcome information by directly evaluating the impact that sample selection has on the properties of a treatment effect estimator, (2) it respects the different roles of covariate distributions in the population and RCT samples, and (3) it is more interpretable than existing metrics. We derive the theoretical properties of the EI for a commonly used propensity-based weighted estimator, where the propensity score is the probability of selection into the RCT. We also propose a method for estimating the EI and we demonstrate this method via simulation studies and two real data applications. Based on our simulation results, we suggest rules of thumb for when the EI can be reliably estimated. Our simulation and real data application results also highlight situations in which the EI would disagree with other extendibility metrics, such as when there are relatively small portions of the target population that are not well-represented by the trial.We also explore using the EI to inform inference on average treatment effects for subpopulations. For situations in which estimation of treatment effects for prespecified subgroups is of interest, we propose a variation of the EI that evaluates the extendibility of the study both to the overall target population and to specific target subpopulations. Often, the desired target population may be too broad for reasonable extension of inferences from an RCT. The EI can be used as a method for determining that a target population is too broad, and we also show that it can be used to select a more reasonable target subpopulation. Once this target subpopulation has been chosen, one should consider how propensity model misspecification in the analysis of a subpopulation average treatment effect may impact estimation. Our theoretical results and simulated data examples suggest that re-estimating the propensity model using only the subsample of the data corresponding to the subpopulation is beneficial to estimating a target subpopulation average treatment effect.

Safety and Effectiveness of ChondroT for Knee Osteoarthritis A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 2a Clinical Trial

최지민 동신대학교 대학원 2023 국내박사

Objectives : This clinical trial was conducted as a therapeutic exploratory clinical trial to estimate the optimal dosage and administration by evaluating the safety and efficacy of ChondroT compared with placebo after oral administration to patients with degenerative knee arthritis. Methods : It was designed as an 8-week, randomized, double-blind, placebo-controlled, multi-center therapeutic exploratory clinical trial. After determining whether the inclusion/exclusion criteria were met, only suitable participants were randomly assigned to one of the three groups according to the registration order. Assigned subjects received study drug or placebo for 8 weeks. Reults : Statistical significance was not confirmed for most of the results after 8 weeks of administration, but the Pain VAS Score after 4 weeks of administration was statistically significantly decreased in the ChondroT 2.0 g administration group compared to the control group. As a result of the safety evaluation analysis, there were no significant changes in blood tests, urine tests, blood pressure, pulse rate, body temperature, and electrocardiogram, and no significant adverse reactions occurred in the subjects during the 8-week test Conclusions : In the ChondroT 2.0 g administration group, the Pain VAS Score significantly decreased after 4 weeks compared to the control group, confirming the possibility of improving arthritis symptoms. Therefore, if a larger sample size is secured and a long-term clinical trial is conducted, it is expected that the arthritis therapeutic effect of ChondroT will be confirmed. 본 임상시험은 퇴행성 슬관절염 환자를 대상으로 ChondroT 및 위약을 경구투여한 후 ChondroT의 안전성 및 유효성을 위약과 비교 평가하여 최적의 용법 및 용량을 추정하기 위한 8주, 무작위배정, 이중눈가림, 평행군, 위약대조, 다기관 치료적 탐색 임상시험이다. 선정/제외기준 적합 여부를 판정한 뒤, 적합한 참가자에 한하여 등록된 순서에 따라 세 군 중 한 군으로 무작위 배정하였다. 배정된 시험대상자는 8주간 시험의약품 또는 위약을 복용하였다. 투여 4주 후 Pain VAS 로 1차 유효성 평가를 진행하였고, 투여 8주 후 Pain VAS Score, WOMAC global scores 및 subscores, SF-36, Physical function test, ESR 및 CRP의 변화량으로 2차 유효성 평가를 진행하였다. 그 결과 ChondroT 2.0 g 투여군에서 투여 4주 후 Pain VAS Score가 대조군 대비 통계적으로 유의하게 감소하였으나 그 외 평가에서는 세 군간 통계적으로 유의한 차이가 없었다. 안전성 평가에서는 혈액 검사, 뇨 검사, 혈압, 맥박, 체온, 심전도 검사 모두 임상시험 전후 의미 있는 변화는 없었으며, 8주간의 시험 기간 동안 대상자들에게 ChondroT와 관련 있는 이상 반응은 나타나지 않았다. 결론적으로, ChondroT의 관절염 증상 개선 효과의 가능성과 안전성을 확인하였다. 이에 보다 큰 규모의 표본크기를 확보하고, 장기간의 임상시험을 진행한다면, ChondroT의 관절염 개선 효과를 확인할 수 있을 것으로 기대한다.

Efficacy and Safety of Ato Panax Lotion on Mild Atopic Dermatitis: A Randomized, Double-Blind, Parallel-Groups, Active-Controlled Trial

김수영 대전대학교 일반대학원 2022 국내박사

Purpose : This 4-week clinical trial was conducted to evaluate the efficacy and safety of administering Ato Panax lotion to patients with mild atopic dermatitis. Methods : A total of 50 participants diagnosed with mild atopic dermatitis from February 2019 to May 2020 were randomly assigned to Ato Panax lotion and Physiogel cream groups. Patients in each group applied each product twice a day for four weeks. The change in Transepidermal Water Loss (TEWL) and Stratum Corneum Hydration (SC hydration) was the primary outcome variable, and measurement were taken at the beginning of the trial, Week 2, and Week 4. The secondary outcome evaluation variables comprised intra and inter-group comparisons of TEWL and skin SC hydration change, and Eczema Area and Severity Index (EASI) and Skindex-29 (the Korean version) scores. The EASI scores and IgE values were calculated at the start of the trial and in Week 4. Skindex-29 scores were measured at the beginning of the trial, Week 2, and Week 4. Results: 1. Primary outcome 1) Intra-group comparison of TEWL The intra-group comparison of the TEWL was significantly reduced in Week 2 in the experimental group. Although this subsequently increased in Week 4, this represents a reduction when compared to the commencement of the trial. However, this result was not statistically significant. In the control group, TEWL increased in Weeks 2 and 4, but this result was not statistically insignificant. 2) Intra-group comparison of SC hydration The intra-group comparison of SC hydration significantly increased in Weeks 2 and 4 for both the experimental and control groups. 2. Secondary outcomes 1) Inter-group comparison of TEWL / SC Hydration (1) Regarding TEWL, there was a greater reduction in percutaneous moisture loss in the experimental group than in the control group, and in Week 2 the results were significant. (2) Regarding SC hydration, there was higher moisture content on the skin surface in the experimental group than in the control group, and this result was also statistically significant in Week 2. 2) Intra and inter-group comparison of EASI scores Both experimental and control groups had significantly improved by Week 4. In terms of an inter-group comparison, although the experimental group exhibited a slight improvement, this was not statistically significant. 3) Intra and inter-group comparison of Skindex-29 scores Both the experimental and control groups exhibited a statistically significant reduction during weeks 2 and 4. In terms of an inter-group comparison, the experimental group indicated a slight decrease compared with the control group, and statistically significant results were obtained in Week 4. 4) Serum Total IgE Level The serum total IgE level was reduced in both the experimental and the control groups at Week 4. However, this was not statistically significant, nor was there any statistically significant difference between the two groups. Conclusion With Evening Primrose and Jacho extracts as its active ingredients, Ato Panax lotion has moisturizing, anti-inflammatory, and antimicrobial effects. It was found to improve skin barrier function and clinical and subjective symptoms through its moisturizing effects in participants with mild atopic dermatitis. In comparison with Physiogel cream, which is widely used as a moisturizer for atopic dermatitis, it yields similarly good results. Therefore, Ato Panax lotion is expected to be effective as a moisturizer for patients with mild atopic dermatitis. 목적: 본 임상시험은 경증 아토피 피부염 환자에게 아토 파낙스 로션의 효능과 안전성을 확인하고자 4주간 시행되었다. 방법: 2019년 2월부터 2020년 5월까지 총 50명의 경증 아토피 피부염으로 진단된 참가자들은 아토 파낙스 로션과 피지오겔 크림 그룹에 무작위 배정되었고, 각 그룹의 환자들은 아토피 피부염 환부에 각각의 제품을 1일 2회씩 4주간 도포하였다. 본 연구에서 1차 유효성 평가변수로 경피 수분 손실량 (TEWL)과 피부 표면 수분량 (SC hydration)의 군내 변화량을 평가하였고, 각 측정은 시험 시작일, 2주차, 4주차에 측정하였다. 2차 유효성 평가변수로는 TEWL과 피부 SC hydration의 군간 변화량, Eczema Area and Severity Index (EASI) score 및 Skindex-29 한국판, IgE의 수치의 군내 및 군간 변화량을 평가하였고, EASI sore, IgE 수치는 시험 시작 전과 4주차에 Skindex-29는 시험 시작일, 2주차, 4주차에 측정하였다. 결과: 1. 1차 유효성 평가변수 1) 경피 수분 손실량(TEWL)의 군내 비교 실험군에서 2주차에서 감소하였고 통계적으로 유의였다. 이후 4주차 상승하였는데, 시작일과 비교하면 감소한 결과이며 이는 통계적으로 유의한 결과는 아니었다. 반면, 대조군에서는 2주차, 4주차에 모두 TEWL이 증가하였지만, 통계적으로 유의한 결과는 아니었다. 2) 피부 표면 수분량(SC hydration)의 군내 비교 2주차, 4주차에 실험군과 대조군 모두 상승하는 결과를 보였고, 이는 통계적으로 유의했다. 2. 2차 유효성 평가변수 1) TEWL과 SC hydration의 군간 비교 (1) TEWL의 군간 비교에서는 실험군이 대조군에 비해 경피의 수분 손실의 감소 효과가 더 좋았고, 2주차의 결과는 유의했다. (2) SC hydrationd의 군간 비교에서는 실험군이 대조군보다 더 피부 표면의 수분량이 상승된 결과를 보였고, 이 결과는 2주차에서 통계학적으로 유의했다. 2) EASI score 군내 및 군간 비교 실험군과 대조군 모두 4주차에 개선되었고 유의한 결과를 보였다. 하지만, 군간 비교에서는 실험군이 조금 더 개선되는 결과를 보였으나, 통계학적으로 유의하지 않았다. 3) Skindex-29 score 군내 및 군간 비교 실험군과 대조군 모두 2주차, 4주차에서 유의한 감소를 보였다. 군간 비교에서는 실험군이 대조군보다 조금 더 감소하는 결과를 보였고, 4주차에서는 통계학적으로 유의한 결과를 얻었다. 4) 총 IgE 수치 총 IgE 수치는 실험군과 대조군 모두 4주차에 감소하는 결과를 보였으나, 이는 유의한 결과는 아니었고, 군간 비교에서도 통계학적으로 유의한 차이를 보이지 않았다. 결론: 아토 파낙스 로션은 달맞이꽃과 자초 추출물을 유효성분으로 하여 보습, 항염증, 항균 작용이 있다. 아토 파낙스 로션은 경증 아토피 피부염 환자에게 보습효과를 통하여 피부 장벽 기능을 개선하고, 임상적 증상 및 호소하는 주관적 증상을 호전시키는 결과를 얻었다. 이는 현재 아토피 피부염의 보습제로 널리 사용되는 피지오겔 크림과 비교하여 유사하거나 좋은 결과를 보여, 아토 파낙스 로션은 경증 아토피 피부염 환자에게 보습제로서 효과가 있을 것으로 기대된다.

Effect of Bangpungtongseongsangamibang on chronic idiopathic urticaria: A double-blind, randomized, placebo-controlled trial

양태규 경희대학교 대학원 2016 국내박사

Objectives: Chronic idiopathic urticaria tends to persist without improvement of symptoms or remission despite conventional treatment. Bangpungtongseongsangamibang (BTSG) is often used for the treatment of chronic idiopathic urticaria in traditional Chinese medicine (TCM)- centered clinical practice. In this study, we investigated the efficacy and safety of BTSG in the treatment of chronic idiopathic urticaria. Design: Double- blind, randomized, placebo- controlled trial Intervention: Treatment with BTSG for 12 weeks Methods: Thirty- eight participants were randomly assigned to the active group (BTSG) and control group (placebo), and the degree of improvement of urticaria was evaluated using the Urticaria Activity Score 7 (UAS7), a Visual Analog Scale (VAS), and the Dermatology Life Quality Index (DLQI) for 12 weeks. Additionally, the safety of BTSG was explored by conducting aspartate aminotransferase/alanine aminotransferase testing every 4 weeks. The maintenance of improvement or remission of symptoms was evaluated using the UAS7, VAS, and DLQI after an additional 12 weeks of follow- up. Results: Of these 38 participants, 27 completed the study. There were 14 participants in the active group and 13 in the control group. A statistically significant improvement was observed after 12 weeks of BTSG administration based on the UAS7 and VAS evaluations, and the improvement was maintained at the 12 weeks follow- up based on the UAS7 evaluation results. No specific adverse events or abnormal findings were found during the study period. Conclusions: BTSG is effective and safe for the treatment of chronic idiopathic urticaria if it is administered for more than 12 weeks. Key words: chronic idiopathic urticaria, herbal medicine, Bangpungtongseongsangamibang, randomized controlled trial RCT code: KOMCGIRB-2012-15

Clinical Performance of Nanohybrid Resin Composites in Non-Carious Cervical Lesions : One-year Results of a Randomized Controlled Clinical Trial

Chae Lynn Yoon 연세대학교 일반대학원 2024 국내석사

The aim of this study was to evaluate the clinical efficacy of Denfil NX resin composite (Vericom, Chuncheon, South Korea) in the direct restoration of non-carious cervical lesions compared to the existing nanohybrid resin composite, Ceram X SphereTEC One (Dentsply Sirona, Charlotte, USA), in a randomized controlled clinical trial. A prospective, blinded, randomized controlled split-mouth study was conducted on thirty-seven patients (25 females, 12 males; mean age 58.24y; range 33-78y) from the Department of Conservative Dentistry at Yonsei University Dental Hospital. The restorative procedures were performed by eighteen specially instructed and experienced dentists. After exclusion of one pair of restorations with unclear records and inappropriate shade selection, a total of seventy-two class V restorations (DN group: n=36, Denfil NX; CX group: n=36, Ceram X SphereTEC One) were included in the assessment, and each patient had one restoration from each of the two groups. Clinical evaluation was performed by two blinded examiners according to FDI clinical criteria and scoring system at baseline, one month, six months, and one year. The Wilcoxon signed-rank test was used for the analysis of evaluation scores of the two groups for each of the eleven selected criteria. One patient dropped out at the six-month evaluation and another patient was lost to follow-up at the one-year evaluation. As a primary efficacy variable, the retention rate was presented based on the scores of ‘fracture of material and retention (B5)’. All restorations in both groups showed 100% retention rate at the one-month recall. However, in the DN group, one restoration had a partial fracture at the beveled area at the six-month recall, and one additional restoration exhibited a partial fracture in the mesial portion at the one-year evaluation. In the CX group, one restoration had a partial fracture at the cervical margin leading to dentin exposure at the six-month recall. Those were considered clinically unacceptable, resulting in a retention rate of 94.12% and 97.06% in DN group and CX group, respectively. However, none of the restorations were completely lost, and there was no significant difference between the two materials. There were no significant differences between the two groups for the other evaluation criteria, except for ‘adjacent mucosa (C15)’. In this category, the DN group showed an inferior result compared to the CX group (p=0.025), but all restorations were within clinically acceptable limits. This appears to be a secondary outcome associated with inadequate marginal adaptation of the restoration, rather than the restorative material itself. In conclusion, both Denfil NX and Ceram X SphereTEC One exhibited satisfactory retention and similar functional and esthetic clinical performance in the direct restoration of non-carious cervical lesions over the one-year follow-up period. Denfil NX exhibited slightly inferior but clinically fully acceptable biological properties as compared to Ceram X SphereTEC One. 본 연구의 목적은 비우식성 치경부 병소의 직접 수복에 있어서 Denfil NX 복합 레진(DN; Vericom, Chuncheon, South Korea)의 임상적 수행 능력을 무작위 배정 임상 시험을 통해 기존의 나노 하이브리드 복합 레진인 Ceram X SphereTEC One(CX; Dentsply Sirona, Charlotte, USA)과 비교하여 평가하기 위함이다. 연세대학교 치과대학병원 치과보존과에 내원한 37명의 환자를 대상으로 한 전향적 무작위 대조 구강 분할 연구가 진행되었으며, 2명의 교수 및 16명의 전공의를 포함한 총 18명의 술자가 술식을 시행하였다. 기록이 불명확하고 색조 선정 과정의 오류가 있었던 한 쌍의 수복물을 제외하고 총 72개의 5급 와동 수복물이 평가에 포함되었으며, 환자마다 두 그룹에서 각각 하나의 재료로 수복치료를 시행하였다. (DN 그룹: n=36, Denfil NX; CX 그룹: n=36, Ceram X SphereTEC One). 수복물에 대한 임상 평가는 수복 직후(baseline) 및 술 후 1개월, 6개월, 1년 내원 시 선정된 11가지의 FDI 임상기준 및 점수체계에 따라 두 명의 검사자가 시행하였으며, 이를 Wilcoxon signed-rank test를 사용하여 분석하였다. 6개월 평가에서 한 명의 환자가 사망하였고, 1년 평가에서 다른 한 명의 추적관찰이 중단되었다. 1차 유효성 변수로서 ‘fracture of material and retention (B5)’ 점수를 기준으로 유지율을 제시하였다. 6개월 평가 시점에서 두 그룹에서 각각 1개의 수복물과, 12개월 평가 시점에서 DN 그룹에서 추가적인 1개의 수복물의 부분적인 파절이 관찰되어, 이는 임상적으로 부적절한 것으로 평가되었다. 이에 DN 그룹과 CX 그룹의 유지율은 각각 94.12%와 97.06%였다. 그러나 수복물이 완전히 탈락한 경우는 없었으며, 두 그룹 간의 유의미한 차이는 없었다. ‘Adjacent mucosa (C15)’ 항목을 제외한 다른 평가 기준에서는 두 그룹 간에 유의한 차이가 없었으며, 해당 항목에서는DN 그룹이 CX 그룹보다 더 열등한 결과를 보였다. (p=0.025). 그러나 모든 수복물이 임상적으로 허용 가능한 범위 내에 있었으며, 인접 조직의 변화는 수복물 자체보다는 수복물의 부적절한 변연과 관련된 이차적인 결과로 추정된다. 결론적으로, 비우식성 치경부 병소의 직접 복합 레진 수복을 대상으로 한1년의 추적 관찰에서 Denfil NX와 Ceram X SphereTEC one 은 모두 충분한 유지력 및 유사한 기능적, 심미적 임상 수행 능력을 나타내었다. Denfil NX는 Ceram X SphereTEC One에 비해 생물학적 특성이 다소 떨어지나 임상적으로는 완전히 허용 가능한 결과를 보인다.