A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

External challenges for specialists dealing with forensic autopsies.

BACKGROUND: In addition to poor infrastructure, and human resource constraints, forensic medicine specialists in developing countries face many external challenges. OBJECTIVES: We aimed to investigate the prevalence, type, and source of external challenges confronting them including sex, age, religion, deceased's place of residence and the number of accompanying relatives. MATERIALS AND METHODS: This cross-sectional, observational study was conducted between August 2020 and July 2022 at the Mortuary of AIIMS, Bhubaneswar with the approval of the ethical committee. RESULTS: Of note, forensic medicine specialists faced external challenges in about one in five cases (20.5%). Most demands were to either minimise the autopsy procedure (n = 65) or to conduct the autopsy at inappropriate times (n = 58). The demands to minimise the autopsy procedure were significantly associated with the deceased's age (p = 0.046), religion (p = 0.010), socioeconomic class (p = 0.020) and manner of death (p = 0.019). CONCLUSIONS: Our study found that forensic medicine specialists in India face significant external challenges. Avoiding unnecessary complete autopsies, implementing night autopsies, and embracing minimally invasive autopsies are recommended to mitigate these challenges.

Comparison of Efficacy and Safety of Azilsartan and Amlodipine Combination Versus Telmisartan and Amlodipine Combination in Hypertensive Patients: A Non-inferiority Trial.

Introduction Hypertension (HTN) is one of the most common conditions encountered in daily practice in hospitals. Combination therapy is mostly initiated in the management of HTN when target blood pressure is not achieved with monotherapy. There are few studies comparing the antihypertensive effect of a combination of azilsartan and amlodipine with a combination of amlodipine and other angiotensin receptor blockers (ARBs), however, the results are contradictory. The objective of this study was to compare the efficacy and safety of the azilsartan and amlodipine combination versus the telmisartan and amlodipine combination in hypertensive patients. Methods The present study was a prospective, randomized, active-controlled, open-label, parallel-group clinical trial. Hypertensive patients were randomized into two groups of 25 patients each. Baseline evaluations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and high-sensitivity troponin I (hsTnI) were done. Patients were reassessed after 12 weeks of drug therapy with azilsartan 40 mg and amlodipine 5 mg combination or telmisartan 40 mg once daily (QD) and amlodipine 5 mg combination QD. Results The response rate (defined as a reduction of more than 20 mm Hg in SBP or 10 mm Hg in DBP or both from baseline at 12 weeks) for HTN in the test group and control groups was found to be 88% and 96% respectively. The response rate of the azilsartan amlodipine group was found to be non-inferior to the telmisartan amlodipine group (odds ratio, OR, 0.31, p = 0.61) at the end of 12 weeks of drug therapy. At 12 weeks of follow-up, there was a significant decrease in SBP (p < 0.001), DBP (p < 0.001), and hsTnI levels (p < 0.001) in both groups from baseline values. However, differences between the test and control groups for blood pressure and hsTnI were found to be not statistically significant at 12 weeks of follow-up. The most commonly reported adverse effect in both groups was headache. Conclusion Azilsartan amlodipine combination had an 88% response rate, which was non-inferior to the telmisartan and amlodipine combination. Biomarkers such as hsTnI showed a significant decrease in both groups after 12 weeks of follow-up. However, there was no significant difference between the two groups.

Comparative Study of the Effects of Azilsartan and Telmisartan on Insulin Resistance and Metabolic Biomarkers in Essential Hypertension Associated With Type 2 Diabetes Mellitus.

Introduction The complex interplay between the autonomic nervous system, renin-angiotensin-aldosterone system (RAAS), and immunity contributes to the pathogenesis of hypertension in diabetes mellitus. The objective of this study was to investigate and compare the effect of azilsartan and telmisartan on insulin resistance and metabolic biomarkers in patients with both hypertension and type 2 diabetes mellitus. Methods The present study was a prospective, randomized, active-controlled, open-label, parallel-group clinical trial. Patients with grade I or II essential hypertension with type 2 diabetes mellitus were randomized into two groups of 25 patients each. Baseline evaluation of homeostasis model assessment-insulin resistance (HOMA-IR), plasma glucose, insulin, leptin and adiponectin levels, and systolic and diastolic blood pressure (SBP and DBP) of patients was done. Patients were reassessed after 12 weeks of drug therapy with azilsartan 40 mg OD (once daily) or telmisartan 40 mg OD. Results The mean changes in HOMA-IR from the baseline at the end of 12 weeks of treatment were 0.15 (-0.64, 0.94.52) in the azilsartan group and 0.32 (-0.61, 1.26) in the telmisartan group. The mean difference in the changes from the baseline in HOMA-IR between the two groups was 0.3 (-0.87, 1.48), which was not statistically significant. No statistically significant changes were observed between the two groups in metabolic biomarkers (leptin: -0.84, CI: -4.83 to 3.14, and adiponectin: -0.12, CI: -0.62 to 0.37). Systolic (SBP) and diastolic blood pressure (DBP) decreased at the end of the 12-week treatment in both the groups; however, there was no significant difference between the two groups (SBP: -2.6, CI: -10.35 to 5.1, and DBP: -3.0, CI: -7.7 to 1.7). Conclusion Neither azilsartan nor telmisartan had any significant effects on insulin resistance and metabolic biomarkers after 12 weeks of drug therapy in hypertension patients associated with type 2 diabetes mellitus. However, they showed a comparable antihypertensive effect. The adverse effects observed were mild in nature, and their incidence was comparable between the two groups.

Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers.

Introduction Healthcare workers (HCWs) are vulnerable to getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preventing HCWs from getting infected is a priority to maintain healthcare services. The therapeutic and preventive role of ivermectin in coronavirus disease 2019 (COVID-19) is being investigated. Based on promising results of in vitro studies of oral ivermectin, this study was conducted with the aim to demonstrate the prophylactic role of oral ivermectin in preventing SARS-CoV-2 infection among HCWs at the All India Institute of Medical Sciences (AIIMS) Bhubaneswar. Methods A prospective cohort study was conducted at AIIMS Bhubaneswar, which has been providing both COVID and non-COVID care since March 2020. All employees and students of the institute who provided written informed consent participated in the study. The uptake of two doses of oral ivermectin (300 µg/kg/dose at a gap of 72 hours) was considered as exposure. The primary outcome of the study was COVID-19 infection in the following month of ivermectin consumption, diagnosed as per Government of India testing criteria (real-time reverse transcriptase polymerase chain reaction [RT-PCR]) guidelines. The log-binomial model was used to estimate adjusted relative risk (ARR), and the Kaplan-Meier failure plot was used to estimate the probability of COVID-19 infection with follow-up time. Results Of 3892 employees, 3532 (90.8%) participated in the study. The ivermectin uptake was 62.5% and 5.3% for two doses and single dose, respectively. Participants who took ivermectin prophylaxis had a lower risk of getting symptoms suggestive of SARS-CoV-2 infection (6% vs 15%). HCWs who had taken two doses of oral ivermectin had a significantly lower risk of contracting COVID-19 infection during the following month (ARR 0.17; 95% CI, 0.12-0.23). Females had a lower risk of contracting COVID-19 than males (ARR 0.70; 95% CI, 0.52-0.93). The absolute risk reduction of SARS-CoV-2 infection was 9.7%. Only 1.8% of the participants reported adverse events, which were mild and self-limiting. Conclusion Two doses of oral ivermectin (300 µg/kg/dose given 72 hours apart) as chemoprophylaxis among HCWs reduced the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost chemoprophylaxis has relevance in the containment of pandemic alongside vaccine.

Indication-specific pricing of drugs: a utopian idea, a pragmatic proposition or unrealistic in economically constrained settings?

The concept of indication-specific pricing (ISP) of drugs means that the cost of a drug will vary depending on the reasons for its use. ISP is a novel concept and its beneficial or detrimental effects are unknown. Experience from richer countries suggests that it is fraught with many administrative, ethical and regulatory challenges. It seems, though, that prices of some drugs have been set using this model. The barriers, real and potential, to the implementation of ISP in low- and middle-income countries are discussed. Implementation of ISP is impractical in such environments because of the large impoverished population, low frequency of health insurance, generally poor health infrastructure, lack of regulatory oversight, and the fact that most healthcare expenditure is borne personally.

Analysis of the compliance of informed consent documents with good clinical practice guideline.

BACKGROUND: Informed consent document plays an integral part in the process of obtaining informed consent. Although India is fast gaining repute as a preferred clinical trial destination, only few studies have evaluated the compliance of informed consent documents with the Indian Good Clinical Practice guideline. METHODS: Retrospective analysis of consent documents submitted to the institutional ethics committee during the periods January 2007-July 2008 and August 2008-December 2009, for the inclusion of 14 essential information elements outlined in the Indian Good Clinical Practice guideline was carried out. Cumulative scores were given for compliance with the guideline and for vernacular translations of the consent documents. RESULTS: Majority of the informed consent documents analyzed were for academic projects in both periods. There was marked improvement in the documents in terms of compliance with Indian GCP in the period 2008-09. The mean cumulative score for consent documents for academic projects increased significantly from 7.00 ± 0.25 in 2007-08 to 8.57 ± 0.16 in 2008-09. The mean score for consent documents for pharmaceutical sponsored studies also increased from 10.23 ± 0.17 in 2007-08 to 11.31 ± 0.32 in 2008-09. Additionally, greater number of consent documents had been translated into vernacular language in the period 2008-29. CONCLUSIONS: The increased compliance with the good clinical practice guideline and improvement in the mean cumulative scores in 2008-09 was probably the outcome of greater awareness amongst the clinical researchers within the institute.

Reversible posterior leucoencephalopathy syndrome in an elderly male on sunitinib therapy.

AIMS: Reversible posterior leucoencephalopathy syndrome (RPLS) has been reported following the use of anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab, sorafinib and sunitinib. In this report we present a case of RPLS that occurred in an elderly male on sunitinib therapy. METHODS: Other case reports of sunitinib-induced RPLS were reviewed and causality assessment was carried out using the World Health Organization-Uppsala Monitoring Centre criteria and the Naranjo algorithm. RESULTS: Only a few cases of sunitinib-induced RPLS had been reported previously and elevated blood pressure at presentation was common in most of the patients. Our case was clinically similar to the earlier reports and the adverse reaction had a 'probable' relationship with sunitinib intake. CONCLUSIONS: Physicians should monitor and manage elevated blood pressure in patients with sunitinib-induced RPLS.

India's growing participation in global clinical trials.

Lower operational costs, recent regulatory reforms and several logistic advantages make India an attractive destination for conducting clinical trials. Efforts for maintaining stringent ethical standards and the launch of Pharmacovigilance Program of India are expected to maximize the potential of the country for clinical research.

Protective effect of aqueous suspension of dried latex of Calotropis procera against oxidative stress and renal damage in diabetic rats.

Calotropis species have been used in the traditional medicinal system for the treatment of diseases of the liver and abdomen. In view of the antioxidant and anti-hyperglycemic properties of an aqueous suspension obtained from the dried latex of Calotropis procera, the present study was carried out to evaluate its efficacy in affording protection against alloxan induced changes in rat kidney. A single intraperitoneal injection of alloxan (150 mg/kg) in rats produced hyperglycemia within 3 days and altered kidney functions over a period of 90 days. Daily oral administration of the aqueous suspension (100 and 400 mg/kg) in diabetic rats produced anti-hyperglycemic effect that was comparable to that of glibenclamide (10 mg/kg). Unlike glibenclamide, the aqueous suspension did not increase the serum insulin levels in diabetic rats. However, it produced a marked reduction in the levels of urinary glucose and protein and normalized the renal tissue levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) in diabetic rats and the effect was comparable to that of glibenclamide. The protection afforded by the aqueous suspension was also evident from the histological analysis of the renal tissue. Our study shows that by exhibiting antioxidant and anti-hyperglycemic property the aqueous suspension of dried latex of C. procera affords protection against the complications associated with diabetes.

Inhibition of Calotropis procera latex-induced inflammatory hyperalgesia by oxytocin and melatonin.

The latex of the wild growing plant Calotropis procera produces inflammation of the skin and mucous membranes upon accidental exposure. On local administration it elicits an intense inflammatory response due to the release of histamine and prostaglandins that is associated with hyperalgesia. In the present study we have evaluated the anti-inflammatory and antinociceptive activity of oxytocin and melatonin against rat paw edema induced by dried latex (DL) of C procera and compared it with that against carrageenan-induced paw edema. Aqueous extract of DL of C procera or carrageenan (1%) was injected into the subplantar surface of the rat paw and the paw volume was measured at 0, 1, 2, 3, 4, 6, 10, and 24 hours. The associated hyperalgesic response and functional impairment were also evaluated concomitantly by dorsal flexion pain test, motility test, and stair climbing ability test. The inhibitory effect of oxytocin and melatonin on edema formation and hyperalgesic response was compared with dexamethasone. DL-induced edema formation was maximum at 2 hours and was associated with decreased pain threshold and functional impairment. Treatment with melatonin significantly attenuated the edematous response while both oxytocin and melatonin increased the pain threshold and improved functional parameters. Both oxytocin and melatonin significantly inhibited the hyperalgesia associated with DL-induced paw edema. Oxytocin was found to be as effective as melatonin in ameliorating the hyperalgesic response. However, it was found to be less effective than melatonin in attenuating edema formation.