Compensation in Neonatal Clinical Trials: A Perspective.

Well conducted clinical trials are the mainstay for generating evidence on preferred treatments. In order to adequately protect the interests of the trial participants, the Central Licensing Authority of India has formulated guidelines to determine the quantum of compensation in cases of regulatory clinical trial related injury or death. However, these guidelines do not address the nuances of trials recruiting children aged under 16 years, within which, neonates are the most vulnerable population. Thus, there is a need for addressing this lacuna in the current guidelines. This article examines the challenges in determining the quantum of compensation in neonatal clinical trials using the current formula, which is a corollary to the challenges faced by the authors in procuring clinical trial insurance for the Probiotic supplementation for Prevention of Neonatal Sepsis (ProSPoNS) trial. Further, it suggests a template for a differential formula using birthweight of infants, which is one of the many important factors impacting neonatal mortality.

A study to estimate the serum IgA and salivary IgA levels in patients with oral leukoplakia and oral squamous cell carcinoma.

Context: The increasing death rate because of oral cancer is mainly due to its late diagnosis. Tumour markers are often detected in abnormal amounts in blood, urine or saliva of patients with certain types of cancer. Diagnosing cancer through human saliva has advantages such as low invasiveness, minimum cost and easy sample collection. We have used serum immunoglobulin A (IgA) and salivary IgA for our present study. Aims: The aim of present study was to estimate serum and salivary IgA levels in oral leukoplakia and oral squamous cell carcinoma (OSCC) patients. Settings and Design: The study included 40 patients; 10 in the control group, 15 cases with oral leukoplakia and 15 cases with OSCC. Methods and Material: The blood samples and saliva were taken from clinically diagnosed oral leukoplakia and OSCC patients and were tested for IgA levels. Statistical analysis used: The data were analysed using SPSS 16.0. The mean values were compared between the groups by using analysis of variance (ANOVA) followed by post-hoc test for group-wise comparison. P value ≤ 0.05 was considered significant. Results: It was observed that the comparison of levels of serum IgA in control and leukoplakia group; control and OSCC group; leukoplakia and OSCC group were found to be statistically significant. Also, comparison between the levels of salivary IgA in control and OSCC group was found to be statistically significant. Conclusion: It is suggested that the serum and salivary IgA levels could be a better adjuvant diagnostic marker along with routine markers in patients with premalignant and malignant lesions.

Study protocol for economic evaluation of probiotic intervention for prevention of neonatal sepsis in 0-2-month old low-birth weight infants in India: the ProSPoNS trial.

INTRODUCTION: The ProSPoNS trial is a multicentre, double-blind, placebo-controlled trial to evaluate the role of probiotics in prevention of neonatal sepsis. The present protocol describes the data and methodology for the cost utility of the probiotic intervention alongside the controlled trial. METHODS AND ANALYSIS: A societal perspective will be adopted in the economic evaluation. Direct medical and non-medical costs associated with neonatal sepsis and its treatment would be ascertained in both the intervention and the control arm. Intervention costs will be facilitated through primary data collection and programme budgetary records. Treatment cost for neonatal sepsis and associated conditions will be accessed from Indian national costing database estimating healthcare system costs. A cost-utility design will be employed with outcome as incremental cost per disability-adjusted life year averted. Considering a time-horizon of 6 months, trial estimates will be extrapolated to model the cost and consequences among high-risk neonatal population in India. A discount rate of 3% will be used. Impact of uncertainties present in analysis will be addressed through both deterministic and probabilistic sensitivity analysis. ETHICS AND DISSEMINATION: Has been obtained from EC of the six participating sites (MGIMS Wardha, KEM Pune, JIPMER Puducherry, AIPH, Bhubaneswar, LHMC New Delhi, SMC Meerut) as well as from the ERC of LSTM, UK. A peer-reviewed article will be published after completion of the study. Findings will be disseminated to the community of the study sites, with academic bodies and policymakers. REGISTRATION: The protocol has been approved by the regulatory authority (Central Drugs Standards Control Organisation; CDSCO) in India (CT-NOC No. CT/NOC/17/2019 dated 1 March 2019). The ProSPoNS trial is registered at the Clinical Trial Registry of India (CTRI). Registered on 16 May 2019. TRIAL REGISTRATION NUMBER: CTRI/2019/05/019197; Clinical Trial Registry.

Exploring the multiple conformational states of RNA genome through interhelical dynamics and network analysis.

The structural variation of RNA is often very transient and can be easily missed in experiments. Molecular dynamics simulation studies along with network analysis can be an effective tool to identify prominent conformations of such dynamic biomolecular systems. Here we describe a method to effectively sample different RNA conformations at six different temperatures based on the changes in the interhelical orientations. This method gives the information about prominent states of the RNA as well as the probability of the existence of different conformations and their interconnections during the process of evolution. In the case of the SARS-CoV-2 genome, the change of prominent structures was found to be faster at 333 K as compared to higher temperatures due to the formation of the non-native base pairs. ΔΔG calculated between 288 K and 363 K are found to be 10.31 kcal/mol (88 nt) considering the contribution from the multiple states of the RNA which agrees well with the experimentally reported denaturation energy for E. coli α mRNA pseudoknot (∼16 kcal/mol, 112 nt) determined by calorimetry/UV hyperchromicity and human telomerase RNA telomerase (4.5-6.6 kcal/mol, 54 nt) determined by FRET analysis.

Fabrication and evaluation of antimicrobial biomimetic nanofiber coating for improved dental implant bioseal: An in vitro study.

BACKGROUND: A weak implant-soft tissue interface may lead to bacterial ingression, breakdown of underlying tissues, and eventually implant failure. This study proposes a surface modification technique of titanium alloy (Ti), using a nano-biopolymer scaffold to enhance soft tissue attachment in dental implants. METHODS: Gelatin (20% w/v) embedded with 10 ± 2 nm silver nanoparticles (AgNPs) was electrospun to form a gelatin electrospun mat (GEM) scaffold, bonded to Ti alloy surface using chemical surface functionalization. Antimicrobial activity of AgNPs was tested against representative Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) at 4, 24, and 48 hours and after embedding in scaffold at 48 hours. Cytotoxicity analysis (MTT assay) was performed using the 3T3 mouse fibroblast cell line at 24 and 72 hours for two groups: control (unmodified Ti disc) and experimental (GEM embedded with AgNPs); and further validated by scanning electron microscopy. RESULTS: The AgNPs-embedded GEM showed good antimicrobial activity at 48 hours, with the AgNPs showing complete (99.99%) inhibition of bacterial colony counts at 24 and 48 hours. Cell viability and proliferation over the GEM modified Ti discs were seen to be significantly increased (P < 0.05) at 72 hours as compared with control. SEM images revealed intimate spreading of fibroblasts, with differentiated cell morphology and pseudopodial processes, indicative of enhanced fibroblastic adhesion, growth, and differentiation over the scaffold. CONCLUSION: Results show good antifouling properties and biocompatibility of the fabricated coating, making it a promising strategy to reduce postoperative infections and peri-implant diseases in Ti dental implants.

Temperature-Dependent Conformational Evolution of SARS CoV-2 RNA Genome Using Network Analysis.

Understanding the dynamics of the SARS CoV-2 RNA genome and its dependence on temperature is necessary to fight the current COVID-19 crisis. Computationally, the handling of large data is a major challenge in the elucidation of the structures of RNA. This work presents network analysis as an important tool to see the conformational evolution and the most dominant structures of the RNA genome at six different temperatures. It effectively distinguished different communities of RNA having structural variation. It is found that at higher temperatures (348 K and above), 80% of the RNA structure is destroyed in both the SPC/E and mTIP3P water models. The thermal denaturation free energy change ΔΔG value calculated for the long-lived structure at higher temperatures of 348 and 363 K ranges from 2.58 to 2.78 kcal/mol for the SPC/E water model, which agrees well with the experimentally reported thermal denaturation free energy range of 2.874 kcal/mol of SARS CoV-NP at normal pH. At higher temperatures, the stability of RNA conformation is found to be due to the existence of non-native base pairs in the SPC/E water model.

Influence of Qualification and Practice Settings of Dental Practitioners on Antimicrobial Prescribing in Delhi and National Capital Region, India.

BACKGROUND AND OBJECTIVES: Inappropriate antimicrobial prescribing is highly reported in dentistry. The objective of the study was to see the effect of dental qualification and practice settings on antimicrobial prescribing practices among dental practitioners in Delhi and National Capital Region (NCR) of India. MATERIALS AND METHODS: A self-designed and pretested questionnaire was given to 667 dental practitioners holding degrees of graduation, postgraduation, and those pursuing postgraduation, working in academic institutions and private clinics in NCR of India. Data were analyzed using statistical software Stata version 12.0. Chi-square and logistic regression tests were used for analysis. RESULTS: Out of total 539 responded, 66.4% of the practitioners prescribed by brand name and 27.8% by generic name. Amoxicillin + clavulanic acid (27.4%) was the first choice. Only 26% of the practitioners asked for antimicrobial susceptibility testing. Space infections (91.9%), impacted third molar extractions (89.7%), and periodontal abscess (88.1%) were the conditions where antimicrobials were most frequently prescribed. However, 60.9% and 53.3% of the practitioners also prescribed antimicrobials for acute pulpitis and dry socket, respectively. For prophylaxis in medical conditions, amoxicillin was the first choice. In case of history of allergy to penicillin, 52.3% of the practitioners prescribe erythromycin whereas 14.6% prescribe amoxicillin. The adverse drug reporting culture was negligible, and only 14.3% of the practitioners were aware of the Pharmacovigilance Program of India. Level of qualification had a significant effect on prescribing (P < 0.05). INTERPRETATION AND CONCLUSION: Frequent irrational prescribing of antimicrobials used in odontogenic conditions warrants an urgent and continued need for guidelines as well as educational intervention programs in dentistry. This will improve the quality of antimicrobial prescribing practices in dentistry.