A methodological analysis of CTRI registered clinical trials on ayurveda interventions for COVID-19 management.

BACKGROUND: Clinical trial protocols provide important methodological information and are expected to be detailed. During COVID-19 pandemic several studies has been registered on CTRI regarding ayurveda for COVID-19. However, there is accumulating evidence that many protocols do not address important study elements. Therefore it is critical to analyze the clinical trial protocols and methodology of ayurveda clinical trials regarding COVID-19 registered on CTRI. OBJECTIVE: To assess the methodological aspects of CTRI registered ayurveda trial for COVID-19, based upon available trial protocols, during 2020 and 2021. MATERIALS AND METHODS: We searched the CTRI database for interventional trials protocols regarding ayurveda for COVID-19, during the year 2020 and 2021. We assessed the protocols for several methodological aspects such as study design, sample size, randomization, blinding, intervention (duration and type) and outcomes. RESULTS: Total 140 clinical trial protocols were analyzed. The highest numbers of studies were registered in May, June, and July 2020 with steady decline thereafter despite rising COVID-19 cases. Total 90 trials were randomized and only 29 are blinded, however majority of the trials did not mention methods of randomization and blinding. Sample size in hospital-based studies ranged from 30 -500 and in community-based studies from 500-80000, however, sample size calculation details were not mentioned in the protocol. Most common intervention used were guduchi, ashwagandha, yashtimadhu, AYUSH-64, curcumin and chyavanprash. CONCLUSION: Although there was a surge of clinical trials on CTRI regarding ayurveda for COVID -19, the methodological quality is not up to the mark with large scope for improvement.

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period. Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.

Pain perception in chronic knee osteoarthritis with varying levels of pain inhibitory control: an exploratory study.

Background and aims Pain is a disabling symptom in knee osteoarthritis (KOA) and its underlying mechanism remains poorly understood. Dysfunction of descending pain modulatory pathways and reduced pain inhibition enhance pain facilitation in many chronic pain syndromes but do not fully explain pain levels in chronic musculoskeletal conditions. The objective of this study is to explore the association of clinical variables with pain intensity perception in KOA individuals with varying levels of Conditioned Pain Modulation (CPM) response. Methods This is a cross-sectional, exploratory analysis using baseline data of a randomized clinical trial investigating the effects of a non-invasive brain stimulation treatment on the perception of pain and functional limitations due to KOA. Sixty-three subjects with KOA were included in this study. Data on pain perception, mood perception, self-reported depression, physical function, quality of life, and quantitative sensory testing was collected. Multiple linear regression analysis was performed to explore the association between the clinical variables with pain perception for individuals with different levels of CPM response. Results For KOA patients with limited CPM response, perception of limitations at work/other activities due to emotional problems and stress scores were statistically significantly associated with pain scores, F(2, 37) = 7.02, p < 0.01. R-squared = 0.275. For KOA patients with normal CPM response, general health perception scores were statistically significantly associated with pain scores, F(1, 21) = 5.60, p < 0.05. R-squared = 0.2104. Limitations of this study include methodology details, small sample size and study design characteristics. Conclusions Pain intensity perception is associated differently with clinical variables according to the individual CPM response. Mechanistic models to explain pain perception in these two subgroups of KOA subjects are discussed.

Impact of Therapeutic Interventions on Pain Intensity and Endogenous Pain Modulation in Knee Osteoarthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: To study the impact of therapeutic interventions on pain analgesia and endogenous pain modulation in knee osteoarthritis (KOA). DESIGN: Systematic review and meta-analysis. METHODS: We searched for KOA randomized clinical trials and observational studies with data on therapeutic interventions comparing pain intensity, temporal summation (TS), and conditioned pain modulation (CPM) scores relative to control. These data were pooled as Hedge's g. To study the relationship between pain intensity and TS/CPM, we performed metaregression with 10,000 Monte-Carlo permutations. RESULTS: We reviewed 11 studies (559 participants). On studying all the interventions together, we found no significant changes in pain modulation, TS, or CPM. Our findings show that this lack of difference is likely because surgical and nonsurgical interventions resulted in contrary effects. Metaregression significantly correlated pain reduction with normalization of TS and CPM. CONCLUSIONS: We demonstrate an association between pain reduction and TS/CPM normalization. Though we cannot directly compare these interventions, the results allow us to draw hypotheses on potential practice schemas. Recovering defective endogenous pain modulation mechanisms may help establish long-term analgesia. However, to validate these paradigms as robust clinical biomarkers, further investigation into their mechanisms would be necessary. The registration number for this review is CRD42017072066.

Treatment of Oral Leukoplakia with Diode Laser: a Pilot Study on Indian Subjects.

BACKGROUND: To evaluate the safety, convenience and effectiveness of 940nm diode laser for treatment of homogenous leukoplakia. MATERIALS AND METHODS: Ten patients having homogenous leukoplakia which were diagnosed clinically were selected from an Indian dental educational institution for the study. Toludine blue staining was applied locally over the lesion. The area where there was increased uptake of stain was excised using a 940 nm EZLASE TM diode laser (BIOLASE-USA). RESULTS: Although various treatment modalities have been tried and the search continues for novel treatment modalities for complete removal of homogenous leukoplakia, from results of our preliminary pilot study it is clear that the use of 940 nm diode laser as a treatment modality for homogenous leukoplakia is a good substitute. Healing was perfect without any complication within a duration of 1 month. Pain intensity was also mild and absolutely zero on the VAS scale after 1 month follow up. CONCLUSIONS: 940 nm diode lasers are safe and can be effectively used as a treatment modality of homogenous leukoplakia, without any complication and without compromising health and oral function of patients. Considering recurrence factor, long term follow up for patients is a must.

Peripheral ossifying fibroma in the oral cavity: MRI findings.

The peripheral ossifying fibroma, a benign gingival overgrowth, occurs mainly in the anterior portion of the maxilla in young adults. The size of the lesion is usually less than 1.5 cm. We report a case of peripheral ossifying fibroma overlying the mandibular alveolar ridge of a 55-year-old female. MR scans showed a large exophytic soft tissue mass overlying mandibular alveolar ridge. The tumor revealed peripheral calcifications with slight erosion of adjacent cortical plate.