Clinical Trial Registry Of India Research Articles

Comparison of clinical effectiveness of propofol auto co-induction and midazolam propofol co-induction using the priming principle among patients undergoing surgeries

Introduction and Aim: Anaesthesia is a balance between adequate usage of anaesthetic drugs and the state of arousal of the patient. Inadequate dose of anaesthesia leads to increased incidence of awareness, while administration of generous drugs leads to complications such as hemodynamic instability and delayed recovery. The objective of the present study was to investigate the clinical effectiveness of propofol auto co-induction (PP) and midazolam propofol co-induction (PM) using the priming principle among patients undergoing surgeries. Materials and Methods: A prospective, randomized and comparative study, recruited 80 patients who were admitted for elective surgeries was carried out after the approval from institutional ethics committee approval and the trial was registered with the clinical trial registry-India (CTRI). Patients were randomly divided into 2 groups: PP group, where patients received 0.4mg/kg of propofol and PM group, where patients received 0.05mg/kg of midazolam. This was followed by propofol induction (2 mg/kg)-10mg every 15 seconds until a BIS value of 45 was attained in both groups. The collected data was assessed for the normality using the Shapiro-Wilk test. A p-value greater than 0.05 (>0.05) was considered to check the normality. The Student’s t-test and Mann-Whitney U test was used to analyse parametric data and non-parametric data before and after the intervention, respectively. Results: The results depicted a significantly reduced requirement of propofol (induction dose) in the PM group. Conclusion: Pre-dosing with Midazolam significantly decreases the induction dose (propofol) requirement without affecting hemodynamic stability.

Dry Swab-Based Nucleic Acid Extraction vs. Spin Column-Based Nucleic Acid Extraction for COVID-19 RT-PCR Testing: A Comparative Study.

Conventional nucleic acid extraction involves usage of spin columns to isolate the RNA, but this is labor intensive. This study compares the spin column method with a dry swab-based method of extraction using a proteinase K buffer and subsequent heat inactivation. A total of 56 subjects were tested for COVID-19 by RT-PCR with probes targeting the E and RdRp genes by collecting two nasopharyngeal and two oropharyngeal swabs and subjecting one set to nucleic acid extraction by spin column and the other set to dry swab-based methods. Out of the 56 samples tested, 27 were positive for VTM-based extraction and 29 were negative. Dry swab-based extraction produced 22 positive results (sensitivity = 81.48%) and 34 negative results. The E gene was detectable in 25 samples by the dry swab method out of 27 samples that tested positive by the VTM-based method (sensitivity = 92.5%). The RdRp gene was detectable in 22 samples by the dry swab method out of 27 samples that tested positive by the VTM-based method (sensitivity = 81.48%). Concordance was 91% with discordance at 9% and a Kappa value of 0.82, indicating almost perfect agreement between the two methods. Our findings indicate that the dry swab method of nucleic acid extraction is a useful alternative to conventional spin column-based extraction with comparable sensitivity and specificity. The trial was registered with the Clinical Trials Registry of India (CTRI) with a CTRI registration number of CTRI/2021/12/038792.

Outcomes and evaluation of endoscopic retrograde cholangiopancreatography via Gastro-Laryngeal Tube in adult patients: a prospective randomised control study

ABSTRACT Objectives In conventional endoscopic retrograde cholangiopancreatography (ERCP), the patient lies prone or in a semi-prone position under deep sedation and maintains spontaneous ventilation. Sedative-induced respiratory depression and unprotected airway compromise patients’ safety. The gastro-laryngeal tube (G-LT) is a novel reusable supraglottic airway device with two separate ports for endoscopy and ventilation. This study attempts to evaluate the performance characteristic of G-LT. Methods One hundred and forty patients undergoing ERCP were enrolled and randomized. In Group G, patients underwent ERCP with G-LT, whereas Group S patients underwent ERCP conventionally. G-LT insertion attempts, esophageal visualization times, vital parameters, propofol consumption, endoscopists’ and anesthesiologists’ satisfaction scores, time to achieve Modified Aldrete Score of ≥ 9, and complications were recorded. Results Both groups showed similar demographic parameters and 100% procedure completion rates. G-LT group showed shortened esophageal visualization times (4.71 ± 1.687 s vs 7.37 ± 1.515 s) and increased propofol consumption (423.14 ± 106.982 mg vs 178.00 ± 100.125 mg). Group G showed better endoscopic maneuvrability and lesser hemodynamic variability. Sore throat, dysphagia, and mucosal trauma were higher in the G-LT group. Conclusion G-LT provides less intra-procedural hemodynamic changes, quicker esophageal visualization, and better scope maneuvrability at the cost of higher propofol consumption, sore throat, dysphagia, and mucosal trauma. Trial Registration Clinical Trial Registry of India CTRI/2021/06/034212 (Registered on: 14/06/2021)

Safety and efficacy of Placida® (fixed dose combination of flupentixol 0.5 mg and melitracen 10 mg) in comparison to escitalopram 10 mg and clonazepam 0.5 mg in patients with comorbid anxiety and depression: a randomized, double blind, double dummy, parallel group clinical trial

Background: Individuals with major depressive disorder (MDD) commonly present with comorbid anxiety and have greater depressive illness severity and chronicity, more suicide attempts, and completions. This randomized, double blind, double dummy, parallel-group clinical phase IV trial (CTRI/2022/11/047050) is aimed to compare the safety and efficacy of Placida® (FDC of flupentixol 0.5 mg + melitracen 10 mg) versus escitalopram + clonazepam in patients with comorbid anxiety and depression. Methods: This is a randomized, controlled, double blind, double dummy, parallel-group, phase IV trial. A total of 440 patients was enrolled across 11 sites in India who fulfilled the inclusion and exclusion criteria. All the subjects will be followed up for 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks with a buffer period of 1 week in each visit. The patient will be checked for severity of adverse events (AEs) and serious adverse events (SAEs). Efficacy will be assessed using the Hamilton depression rating scale (HAM-D), Hamilton anxiety rating scale (HAM-A) at baseline, weeks 4, 8 and 16, 24 score-reduction rate from baseline to end of treatment and extrapyramidal symptom rating scale (ESRS) at week 16 and end of the study. The first enrolment was done on 26 November 2022 and presently the subjects are under follow-up stage. The anticipated completion date for the study is March 2024. Conclusions: Outcomes of this trial will provide valuable information on safety and efficacy of Placida® as compared to escitalopram and clonazepam in treating patients with comorbid anxiety and depression. Trial Registration: The trial is registered with clinical trial registry India (CTRI/2022/11/047050) prospectively.

Safety and immunogenicity of a new formulation of a pentavalent DTwP-HepB-Hib vaccine in healthy Indian infants-A randomized study.

Pentavalent vaccines (DTP-HepB-Hib) have been introduced in many countries in their routine public immunization programmes to protect against diphtheria (D), tetanus (T), pertussis (P), hepatitis B (Hep B) and Hemophilus influenzae type b (Hib) diseases. This study compared the safety and immunogenicity of a new formulation of a whole-cell Bordetella pertussis (wP) based pentavalent vaccine (DTwP-HepB-Hib). The new formulation was developed using well-characterized hepatitis B and pertussis whole cell vaccine components. This was a phase III, observer-blind, randomized, non-inferiority, multi-center study conducted in India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator formulations at 6-8, 10-12 and 14-16 weeks of age. The investigational formulation of DTwP-HepB-Hib vaccine was non-inferior to the licensed formulation in terms of hepatitis B seroprotection rate (% of subjects with HepB antibodies ≥10mIU/mL were 99.1% versus 99.0%, respectively, corresponding to a difference of 0.1% (95% CI, -2.47 to 2.68)) and pertussis immune responses (adjusted geometric mean concentrations of antibodies for anti-PT were 76.7 EU/mL versus 63.3 EU/mL, with a ratio of aGMTs of 1.21 (95% CI, 0.89-1.64), and for anti-FIM were 1079 EU/mL versus 1129 EU/mL, with a ratio of aGMTs of 0.95 (95% CI, 0.73-1.24), respectively). The immune responses to other valences (D, T, and Hib) in the two formulations were also similar. The safety profile of both formulations was found to be similar and were well tolerated. The investigational DTwP-HepB-Hib vaccine formulation was immunogenic and well-tolerated when administered as three dose primary series in infants. Clinical Trials Registry India number: CTRI/2018/12/016692.

Functional Duration of Peripheral Intravenous Cannula in Neonates with or without Splint: A Randomized Controlled Trial.

To determine the effect of splint on the functional duration of peripheral intravenous cannula (PIVC) in neonates. The trial was prospectively registered with the Clinical Trial Registry of India (CTRI/2021/09/036337). One-hundred-fifty cannulations in 71 neonates were randomized to splint (n = 75) and no-splint (n = 75) groups, respectively. The median (interquartile range, IQR) functional duration of PIVC was calculated from the time of PIVC insertion till removal due to the development of signs of PIVC failure or treatment completion. Kaplan-Meier survival analysis was used to compute the time to complication of PIVC.Complications related to PIVC were noted and multivariate Cox-proportion hazard analysis was done to find the predictors associated with PIVC failure. Median (IQR) functional duration of PIVC in the splint and the no-splint group was 28 (23-48) and 30 (25-48) h, respectively (p = 0.477). PIVC duration was higher in the splint group in term neonates and the no-splint group in preterm neonates; however, the differences were not statistically significant. No difference was observed in continuous vs. intermittent infusion subgroups. Time to complication development was also comparable between the groups. Splint application did not affect functional PIVC duration and its related complications in neonates.

Statistical analysis plan and protocol updates for Gestational diabetes in Uganda and India: Design and Evaluation of Educational Films for Improving Screening and Self-management (GUIDES) trial

BackgroundTimely detection and management of gestational diabetes mellitus (GDM) have been identified as a high priority for policymakers in low- and middle-income countries (LMICs). The GUIDES trial will evaluate a package of three interconnected film-based interventions aimed at improving the timely detection and management of GDM. The protocol for this trial has previously been published; this publication outlines the statistical analysis plan for the trial.Methods and designThe GUIDES study is a multi-country cluster-randomised controlled trial consisting of one trial conducted in Uganda and one in India (30 clusters in each country). Mixed effects models will be used to compare the primary study outcomes of the proportion of women who are tested for GDM between 24 and 32 weeks of pregnancy and the mean fasting blood sugar of women with GDM at 34-week follow-up while accounting for clustering. Secondary analyses will compare the proportion of women with self-reported GDM diagnosis at 32 weeks of pregnancy and the proportion of women with adverse perinatal outcomes related to GDM up to 4 weeks after birth in each trial arm.Trial status and discussionFollow-up is expected to end in March 2023 in Uganda and in May 2023 in India. Analyses will be carried out following this statistical analysis plan in the month following trial completion.Trial registrationClinicalTrials.gov NCT03937050. Registered on 3 May 2019. Clinical Trials Registry India CTRI/2020/02/023605. Registered on 26 February 2020.

Effect of overground gait training with ‘Mobility Assisted Robotic System-MARS’ on gait parameters in patients with stroke: a pre-post study

ObjectiveTo observe the effect of overground gait training with ‘Mobility Assisted Robotic System-MARS’ on gait parameters in patients with stroke.Patients & methodsThis prospective pre-post study was conducted in a tertiary teaching research hospital with 29 adult stroke patients, with age up to 65 years. Patients fulfilling the inclusion criteria were divided in 2 groups based on the duration of stroke (≤ 6 months-sub-acute & > 6 months-chronic stroke) and provided overground gait training with MARS robot for 12 sessions (1 h/session) over a period of 2–3 weeks. Primary outcome measures were; 10-Meter walk test-10MWT, 6-min’ walk test-6MWT and Timed up & Go-TUG tests. Secondary outcome measures were Functional Ambulation Category-FAC, Modified Rankin Scale-MRS and Scandinavian Stroke Scale-SSS.ResultsNo adverse events were reported. Twenty-five patients who were able to perform 10-MWT at the beginning of study were included in the final analysis with 12 in sub-acute and 13 in chronic stroke group. All primary and secondary outcome measures showed significant improvement in gait parameters at the end of the training (p < 0.05) barring 10-Meter walk test in sub-acute stroke group (p = 0.255). Chronic stroke group showed significant minimum clinically important difference-MCID difference in endurance (6MWT) at the end of the training and both groups showed better ‘minimal detectable change-MDC’ in balance (TUG) at the end of the training.ConclusionsPatients in both the groups showed significant improvement in walking speed, endurance, balance and independence at the end of the training with overground gait training with MARS Robot.Clinical trial registryNational Clinical Trial Registry of India (CTRI/2021/08/035695,16/08/2021).

Investigator knowledge, awareness, and registrations of academic clinical trials with the Clinical Trial Registry of India: An observational study.

In 2019, the Central Drugs Standard Control Organization (CDSCO) introduced the New Drugs and Clinical Trials Rules 2019 (NDCTR), which separated the research guidelines for "Clinical Trials" and "Biomedical and Health Research." As a result, guidelines issued by Indian Council of Medical Research were stated to apply to academic clinical trials (ACTs). This change is important because academic studies are crucial for scientific advancement and repurposing of approved drugs in health-care industry. However, conducting an ACT can pose challenges. We assessed the level of awareness, knowledge, and challenges faced by investigators. Our aim is to overcome some of these challenges and encourage more academic studies for the betterment of healthcare and scientific knowledge in India. The study was conducted in two phases after obtaining approval from the Institutional Ethics Committee (EC) of three tertiary care hospitals in Mumbai. In the first phase, the number of ACTs was assessed from the clinical trial registry India website, while the number of registered and re-registered ECs were assessed from the CDSCO website. The second phase involved assessing investigator awareness and knowledge about ACTs using a prevalidated questionnaire with a content validity index score of 0.93. In 2020, the highest numbers of studies were registered, with the highest numbers of registered and re-registered ECs from Maharashtra. All participants completed the questionnaire and were aware of the need to follow guidelines for clinical trials. Sixty-seven percent of participants knew that the guidelines for ACTs differed from those of sponsored clinical trials, but only 58% were aware of the exact definition of an ACT as per NDCTR, 2019. Eighty-five percent of participants knew who could initiate an ACT, but only 27% knew about the applicability of results of an ACT and 33% had in-depth knowledge about the required approvals, while only 10% knew the archival period. Although 71% of participants had knowledge about serious adverse event reporting, few answered in-depth questions correctly. Only 31 participants reported facing varied challenges. To conduct ACTs effectively and contribute to healthcare and scientific advancement, it is crucial to enhance investigators' existing knowledge about ACTs.

Nutritional support for adult patients with microbiologically confirmed pulmonary tuberculosis: outcomes in a programmatic cohort nested within the RATIONS trial in Jharkhand, India

Undernutrition is a common comorbidity of tuberculosis in countries with a high tuberculosis burden, such as India. RATIONS is a field-based, cluster-randomised controlled trial evaluating the effect of providing nutritional support to household contacts of adult patients with microbiologically confirmed pulmonary tuberculosis in Jharkhand, India, on tuberculosis incidence. The patient cohort in both groups of the trial was provided with nutritional support. In this study, we assessed the effects of nutritional support on tuberculosis mortality, treatment success, and other outcomes in the RATIONS patient cohort. We enrolled patients (aged 18 years or older) with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units. Patients received nutritional support in the form of food rations (1200 kcal and 52 g of protein per day) and micronutrient pills. Nutritional support was for 6 months for drug-susceptible tuberculosis and 12 months for multidrug-resistant tuberculosis; patients with drug-susceptible tuberculosis could receive an extension of up to 6 months if their BMI was less than 18·5 kg/m2 at the end of treatment. We recorded BMI, diabetes status, and modified Eastern Cooperative Oncology Group (ECOG) performance status at baseline. Clinical outcomes (treatment success, tuberculosis mortality, loss to follow-up, and change in performance status) and weight gain were recorded at 6 months. We assessed the predictors of tuberculosis mortality with Poisson and Cox regression using adjusted incidence rate ratios (IRRs) and adjusted hazard ratios (HRs). The RATIONS trial is registered with the Clinical Trials Registry of India (CTRI/2019/08/020490). Between Aug 16, 2019, and Jan 31, 2021, 2800 patients (mean age 41·5 years [SD 14·5]; 1979 [70·7%] men and 821 [29·3%] women) were enrolled. At enrolment, 2291 (82·4%) patients were underweight (BMI <18·5 kg/m2), and 480 (17·3%) had a BMI of less than 14 kg/m2. The mean weight and BMI were 42·6 kg (SD 7·8) and 16·4 kg/m2 (2·6) in men and 36·1 kg (7·3) and 16·2 kg/m2 (2·9) in women. During the 6-month follow-up, treatment was successful in 2623 (93·7%) patients, 108 (3·9%) tuberculosis deaths occurred, 28 (1·0%) patients were lost to follow-up, and treatment failure was experienced by five (0·2%) patients. The median weight gain was 4·6 kg (IQR 2·8-6·8), but 1441 (54·8%) of 2630 patients remained underweight. At 2 months, 1444 (54·0%) of 2676 patients gained at least 5% of baseline weight. Baseline weight (adjusted IRR 0·95, 95% CI 0·90-0·99), BMI (0·88, 0·76-1·01), poor performance status (ECOG categories 3-4; 5·33, 2·90-9·79), diabetes (3·30, 1·65-6·72), and haemoglobin (0·85, 0·71-1·00) were predictors of tuberculosis mortality. A reduced hazard of death (adjusted HR 0·39, 95% CI 0·18-0·86) was associated with a 5% weight gain at 2 months. In this study, nutritional support was provided to a cohort with a high prevalence of severe undernutrition. Weight gain, particularly in the first 2 months, was associated with a substantially decreased hazard of tuberculosis mortality. Nutritional support needs to be an integral component of patient-centred care to improve treatment outcomes in such settings. India Tuberculosis Research Consortium, Indian Council of Medical Research.

Comparison of efficacy of intrathecal fentanyl as an adjuvant to bupivacaine and ropivacaine in lower limb orthopaedic surgeries for post-operative analgesia

Background: Sub-arachnoid block or spinal anaesthesia is a common mode of anaesthesia that is used for lower limb orthopaedic surgeries. Bupivacaine hydrochloride is a long-acting amide anaesthetic used extensively intrathecally. It has the ability to effectively block sensory and motor pathways. However, it has drawbacks, like cardiotoxicity and neurotoxicity. Ropivacaine is a long-acting amide local anaesthetic agent. It has the capacity to block sensory nerves more than motor nerves. Ropivacaine has reduced potential for neurotoxicity and cardiotoxicity. Fentanyl is a synthetic opioid. It can be added as an adjuvant to local anaesthetic agents used intrathecally. Fentanyl is characterised by its high potency, rapid serum elimination, and minimal histamine release. The blood-brain barrier can be quickly crossed by fentanyl, which takes one to two minutes to generate analgesia. Objectives: To compare post-operative analgesia in patients receiving bupivacaine with fentanyl and ropivacaine with fentanyl in lower limb orthopaedic surgeries via sub-arachnoid block; onset, duration of analgesia, duration of sensory and motor blockade; study the haemodynamic stability of patients in both groups; compare the requirement of 24 hours rescue analgesia; to compare the incidence of side effects. Methodology: This study will be a comparative interventional study which will be conducted on 60 adult patients of both sexes posted for lower limb orthopaedic surgery. They will be randomly divided into two groups with 30 patients in both groups. Group A: Patients receiving bupivacaine 3 mL with fentanyl 25 µg and Group B: Patients receiving ropivacaine 3mL with fentanyl 25 µg. The onset of and duration of block (sensory as well as motor), hemodynamic parameters, post-operative analgesia time and side effects (if any) will be recorded. Trial registration: Submitted to Clinical Trial Registry of India (CTRI) Trial REF/2023/05/067586

Glycemic index of a nutritional supplement designed for people with chronic kidney disease.

The study was carried out to measure the glycemic index (GI) of an oral food supplement for people with CKD as well as on patients on maintenance dialysis. The study was conducted as per international protocols for testing GI, was approved by the local institutional ethics committee, and was registered with the Clinical Trial Registry of India (CTRI). This was a crossover randomized controlled study which enrolled 15 participants between the ages of 18 and 45 years. The participants were randomly allotted to one group that consumed either the reference food (27.5 g of glucose monohydrate) or 118 g of the nutritional supplement which contained 25 g of available carbohydrates. Fasting capillary blood samples as well as blood samples at different time intervals as per the GI protocol, after consumption of either the supplement or the reference food were taken from the participants. Each testing day was separated by a 3-day washout period. GI was calculated from the incremental area under the blood glucose response elicited by the nutritional supplement as a percentage of the response after the consumption of 25 g of glucose (27.5 g of glucose monohydrate) by the same participant using a standard formula. The GI of the nutritional supplement was calculated to be 10.3 ± 2.0 which is considered to be low as per international GI testing standards. The product was created to supplement the diet of people with CKD at different stages and to help prevent the progression from CKD to ESRD as well as the risk for CVD. This product was found to have a low GI which is desirable for people with CKD as well as diabetics in general who are at risk for developing CKD.

Ethnic representation in interventional clinical trials run in India.

Globally, the need to enhance the diversity of trial participants is receiving increasingly urgent attention. We wanted to know whether trials run in India had adequately sampled the country's enormous ethnic diversity. We accessed the Clinical Trials Registry-India website to determine whether each interventional drug or biologic Phase 2 or 3 study, registered in a recent five-year period had run in each of six geographic zones. As regards Phase 3 trials conducted only in India, 61.4% ran in a single zone and just 6.8% were conducted in all six zones. Multinational Phase 3 trials had a better distribution since 3.6% had run in just one zone and 7.1% in all six. India's diverse ethnic groups are underrepresented in the majority of trials covered in this study. A trial that is conducted on non-representative groups and later discovered to be harmful or ineffective in parts of the population, is unethical. We propose various remedial steps.

Pilates versus Bruegger’s exercises for forward head posture associated with temporomandibular joint dysfunction

Abstract The aim of the trial was to determine and compare the effect of Pilates exercises and Bruegger’s exercises in conjunction with low level laser therapy (LLLT) in forward head posture (FHP) associated with temporomandibular joint dysfunction (TMD). The study was conducted on 30 participants diagnosed with TMD associated with forward head posture. Through randomisation, participants were divided into Pilates (n=15) and Bruegger’s (n=15) exercise groups. LLLT was a common intervention for both the groups. Intervention was given for 3 times a week for 3 weeks. Outcome measures were pain intensity using visual analogue scale (VAS), craniovertebral angle (CVA) using ‘ON Protractor’ software application, range of motion (ROM) of temporomandibular joint (TMJ) using ruler and functional impairment using mandibular function impairment questionnaire (MFIQ) assessed at baseline and 3rd-week post-intervention. A statistically significant difference was noted in pain intensity, ROM of TMJ, CVA and functional impairment with pre- and post-intervention comparison (P&lt;0.001). Between-group analysis showed that Pilates group was better than Bruegger’s exercise group in terms of improving CVA (P&lt;0.001), mouth opening (P&lt;0.01) and reducing functional impairment (P&lt;0.01). However, both the groups were equally effective in in reducing pain intensity (P&lt;0.01). Pilates was better compared to Bruegger’s exercises in reducing functional impairment, improved mouth opening and correcting FHP. Further both the groups were equally effective in reducing pain intensity. Clinical trial registry India: CTRI/2021/09/046969

Effect of Motor Imagery on Corticomotor Excitability and Pain Status in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) has been defined by the American College of Rheumatology in 1987 as a chronic inflammatory disease characterised by joint swelling, joint tenderness, and destruction of synovial joints leading to severe disability and premature mortality. There is a paucity of literature assessing corticomotor excitability in RA patients. This study aimed to assess the effect of motor imagery on corticomotor excitability and pain status in RA patients. The specific objectives were to study the effect of motor imagery on corticomotor excitability and pain status in RA patients. We also wanted to compare thecorticomotor excitability between RA patients with healthy controls. The correlation between the measures of corticomotor excitability and pain status in RA patients has also been done. The study was designed as a pilot clinical trial with a case-control design. Forty participants were recruited for the study. Twenty RA patients were recruited from the Department of Rheumatology and Department of Physical Medicine and Rehabilitation (PMR), AIIMS, New Delhi, and 20 healthy controls. Testing was performed at the Pain Research & rTMS Lab, Department of Physiology, AIIMS, New Delhi. The study was approved by the Institute Ethics Committee, AIIMS New Delhi, and registered in the Clinical Trials Registry-India (CTRI). For the subjective assessment of pain, the visual analogue scale (VAS), Short-Form McGill Pain Questionnaire, WHO-Quality of Life Brief questionnaire (WHO-QOL-BREF), and Rheumatoid Arthritis Pain Scale were used. For the objective assessment of pain, hot and cold pain thresholds were assessed using thermo-tactile quantitative sensory testing (QST) using the method of limits and corticomotor excitability using a transcranial magnetic stimulation device. All participants were also asked to perform motor imagery tasks which consisted of a metronome-paced thumb opposition paradigm. Results: The resting motor threshold (RMT) decreased significantly after motor imagery when compared to the mental calculation group. The amplitude of motor evoked potential (MEP) and QST parametervalue was comparable in both the groups before and after motor imagery and mental calculation. RMT was found to be significantly higher whereas MEP values were found to be significantly lower in RA compared to controls. We conclude that patients suffering from RA have decreased corticomotor excitability compared to controls. Motor imagery was effective in improving corticomotor excitability in these patients and can be used as rehabilitation in RA to relieve their pain.

Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial.

UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM. Clinical trial registry of India (CTRI/2021/03/031864). •Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC). •An association between UCM and intraventricular hemorrhage in preterm neonates < 28weeks of gestation is still being investigated. •Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates. •UCM also increases the need for non-invasive respiratory support compared to DCC.

Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial

BackgroundThere remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens. ObjectivesTo determine the effect of vitamin D or zinc supplementation on recovery from COVID-19. MethodsWe conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers. ResultsWe observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (–2.3 to 13.7); for no vitamin D: –1.4 ng/mL (–5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events. ConclusionsResults suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.

Beneficial immune-modulatory effects of the N-163 strain of Aureobasidium pullulans-produced 1,3-1,6 Beta glucans in Duchenne muscular dystrophy: Results of an open-label, prospective, exploratory case-control clinical study

BackgroundThis exploratory case-control study is to evaluate the effects of supplementation of Aureobasidium pullulans-N-163 strain produced 1,3–1,− 6 beta glucan in young patients with Duchenne muscular dystrophy (DMD). MethodsTwenty-seven male subjects aged 5–19 years with DMD were included, nine in the control arm and 18 in the treatment arm to receive N-163 beta glucan along with conventional therapies for 45 days. While performing the analysis, steroid usage was also taken into consideration, those not administered steroids (Steroid -ve) (Control, n = 5; treatment, n = 9), those administered steroids (Steroid +ve) (Control, n = 4; treatment, n = 9). ResultsIL-6 showed a significant decrease in the treatment groups, especially the N-163 Steroid -ve group. IL-13 decreased in both treatment groups and TGF-β levels showed a significant decrease in the treatment groups, especially the N-163 Steroid –ve group, (p < 0.05). Dystrophin levels increased by up to 32% in the treatment groups compared to the control. Medical research council (MRC) grading showed slight improvement in muscle strength improvement in 12 out of 18 patients (67%) in the treatment group and four out of nine (44%) subjects in the control group. ConclusionSupplementation with the N-163 beta glucan food supplement produced beneficial effects: a significant decrease in inflammation and fibrosis markers, increase in serum dystrophin and slight improvement in muscle strength in DMD subjects over 45 days, thus making this a potential adjunct treatment for DMD after validation. Trial registrationThe study was registered in Clinical trials registry of India, CTRI/2021/05/033346. Registered on 5th May, 2021.

Prospective comparative analysis of intraoperative and postoperative anesthetic and analgesic effect of ultrasound-guided pectoral with serratus anterior plane block versus thoracic paravertebral versus erector spinae blocks in breast oncosurgeries

AbstractAims and Objectives:Different regional anesthetic techniques have been described and are frequently used in breast cancer surgeries to provide efficient pain management and reduce the use of opioids. This study’s main goal was to use pain scores to compare the postoperative analgesic effectiveness of pectoral nerve (PECS 1) block with serratus anterior plane (SAP) block, thoracic paravertebral (TPV) block, and erector spinae plane (ESP) block. Comparing the needs for intraoperative analgesia and postoperative anesthesia was one of the secondary goals.Methods:After institutional ethical committee approval and after prospectively registering this trial with the Clinical Trials Registry of India, 25 patients were randomized and enrolled in each group (Group 1 – PECS 1 and SAP block, Group 2 – TPV group, and Group 3 – ESP group). Standard general anesthesia was administered to all the patients and the blocks, as per randomization were performed before anesthesia induction.Results:The demographic characteristics, intraoperative opioid and sevoflurane consumption, and requirement of rescue analgesia were comparable between the three groups. Pain scores at 0 and 6 h were significantly less in the TPV group when compared to the ESP group and PECS 1 with the SAP group (P= 0.005 andP= 0.006, respectively). Pain scores at 12 and 24 h were comparable between three groups.Conclusion:TPV block provides significantly better pain scores at 0 and 6 h, with comparable pain scores at 12 and 24 h, compared to PECS 1 with SAP block and ESP block with comparable adverse events.

Cost-Efficacy Analysis of Use of Frozen Section Histology for Margin Assessment During Breast Conservation Surgery in Breast Cancer Patients.

Margin assessment is an essential component of breast conservation surgery (BCS). Re-excision of infiltrated margin(s) detected on paraffin section histology (PSH) needs reoperation, adding time, inconvenience and cost. Intra-operative assessment of margins using frozen section histology (IFSH) can potentially obviate need for re-operation, thus facilitating one-step oncologically complete BCS. IFSH and PSH reports of consecutive patients undergoing BCS (2010-2020) were reviewed. Accuracy and cost-efficacy of IFSH were assessed, considering PSH as gold standard. Cost of achieving oncologically complete BCS in whole cohort with IFSH (Scenario-A) was calculated and compared using appropriate statistical tests, with hospital costs for the cohort ina hypothetical Scenario-B, where IFSH was presumed not to have been used and all patients with infiltrated margin(s) on PSH would have been re-operated. Of the 367 patients screened, 39 were excluded due to incomplete IFSH data. Of 328 patients analyzed, 59 (18%) had one or more margins were reported infiltrated on IFSH, managed by re-excision or mastectomy in the same sitting, thus avoiding a reoperation. Additional 8 (2.4%) had involved margins on PSH (False negative IFSH). Significantly higher number of reoperations (p < 0.001) would have been needed in scenario-B. Average cost of the first operation with use of IFSH was Indian Rupees (INR)25791 which included INR660 as IFSH cost. The average cost of reoperation was INR23724 which could be avoided in59 (18%) by use of IFSH. The average cost per patient to achieve oncologically complete surgery in scenario Autilizing IFSH was significantly lower (p = 0.001)by INR3101 (11.7%), c.w. that in scenario B. Significant cost-saving with IFSH was maintained in cost-efficacy analysis undertaken with various higher and lower costs assumptions. Use of IFSH facilitates one-step oncologically complete BCS in majority of patients and results in considerable cost saving, resulting in avoidance of reoperations, besides preventing patient anxiety and delay in adjuvant treatment. Clinical Trials Registry-India (CTRI/2021/08/035896).