Approach to Study the Efficacy and Safety of New Complementary and Alternative Medicine Formulations: Lesson during COVID-19 from Sri Lanka.

COVID-19 affected Sri Lanka from early 2020, a time of considerable ignorance accompanied by wide media coverage of a devastating epidemic in Italy and Europe. Many were attracted to complementary and alternative medicine (CAM) or traditional medicine (TM) in this desperate situation. Several preparations were claimed to be effective against COVID-19 globally. Dammika Bandara Syrup© was one such preparation promoted for preventing and treating SARS-CoV-2 infection. It was based on bees' honey, pericarp and mace of Myristica fragrans (nutmeg), the seed of Foeniculum vulgare and fresh rhizome of Zingiber officinale, all believed to have anti-viral properties. Following an unpublished clinical study claiming efficacy, Dammika Bandara Syrup© gained wide media publicity and political patronage. The producer claimed of Goddess Kali revealing the formula added an anthropological, cultural, and religious complexity to the issue. The demand for the product increased rapidly as a debate raged both in public and in the parliament on utilizing such products in combating COVID-19. The Department of Ayurveda, which is statutorily responsible for regulating CAM/TM had to respond to the situation. The legislation to regulate such indigenous medicinal products was weak, and the crisis deepened as thousands converged to the production facility, defying mobility restrictions introduced to control COVID-19. This led to the Ministry of Health requesting academics to form a team and conduct a clinical trial to prove its efficacy. This paper outlines the process and issues faced during the regulatory approval for the trial in a polarized political environment. Some health professionals accused the researchers of bowing to political pressure and questioned the scientific justification for the trial. However, the team considered this as an opportunity to streamline a path for research into CAM/TM therapies in situations such as COVID-19. Several processes were identified and addressed, such as the provisional registration of CAM preparations, assessing the potential efficacy of a CAM product, confirmation of authenticity and safety, standardization and supervision of production respecting cultural identities, obtaining approval for human use, choice of comparators, and ethical issues. We believe the study has helped set standards and a benchmark for CAM and TM research in Sri Lanka.

Effect of vitamin D therapy on bone mineral density in patients with diabetic nephropathy; a randomized, double-blind placebo controlled clinical trial.

PURPOSE: Diabetes compromises bone strength resulting increased risk of osteoporosis. Objective of this study was to determine the effect of vitamin D given to patients with early diabetic renal disease on BMD and BMC. METHODS: Patients with diabetic nephropathy were recruited. Treatment group received 50,000 IU of vitamin D3 intramuscularly and the control group was given an equal volume of distilled water (0.25 mL) monthly for six months. Baseline BMD, BMC in the total body, lumbar spine and proximal femur were measured by DXA. After six months measurements were repeated. When trial period was over, a randomly selected subgroup of patients (25 from each group) was followed up for further six-months and measurements were repeated. RESULTS: Selected patients were randomly assigned to two groups. After six months, the treatment group total body BMD, total body BMC and BMDs of spine, femoral neck and total hip regions increased by 2.0%, 2.2%, 1.8%, 2.1% and 2.6% (P < 0.05 for all within-group differences), respectively. In the Control group, BMD or BMC of any region mentioned above did not change significantly during the initial 6 months (P < 0.05 for the between-groups differences). After 6 months of stopping treatment, a statistically significant reduction of total BMD and BMC was observed in the treatment group (P = 0.009). CONCLUSION: This study showed that treatment with high dose vitamin D significantly influences total body BMC, total body BMD, BMDs of spine, femoral neck and hip among patients with diabetic nephropathy.

Sequel and therapeutic modalities of leptospirosis associated severe pulmonary haemorrhagic syndrome (SPHS); a Sri Lankan experience.

BACKGROUND: The emergence of leptospirosis-associated severe pulmonary hemorrhagic syndrome (SPHS) with high case fatality has been reported from many countries. Understanding of clinical disease and sequel of SPHS needs larger studies with adequate numbers. The purpose of this study was to describe the characteristics and sequel by different therapeutic approaches for SPHS in Leptospirosis in Sri Lanka. METHODS: This study was conducted at Teaching Hospital-Karapitiya (THK), Galle, Sri Lanka from June 2015 to December 2017. THK is the main tertiary care center for the Southern Province. All confirmed-cases of leptospirosis who presented during this period and were admitted to five medical units of THK were included in this study. SPHS was defined as a patient presenting; haemoptysis, arterial hypoxemia (Acute Lung Injury Score < 2.5), haemoglobin drop (10% from the previous value), or diffused alveolar shadows in the chest radiograph, without alternative explanation other than leptospirosis. RESULTS: Of the 128 MAT confirmed cases of leptospirosis, 111 (86.7%) had acute kidney injury (AKI) whilst SPHS was seen in 80 (62.5%). Patients typically developed SPHS within the first week of illness, mostly on days 4 and 5. The case fatality rate of this study sample was 28.1% (n = 36), while for patients with SPHS, it was 41.5%. Most of the deaths (n = 19) were within the first 3 days of admission (on the same day 8, and within next 48 h 11). Among SPHS patients, 59 received therapeutic plasma exchange (TPE). The survival rate was higher (n = 35, 74.5%) when the TPE was performed within the first 48 h of detecting SPHS compared to patients in whom the procedure was done after 48 h (n = 5, 54.5%). Of the 19 leptosprosis patients with SPHS who did not receive TPE, 17 died (89.5%). However, the group of patients who received TPE was primarily the patients survived beyond day 3. CONCLUSIONS: We observed that during the study period, SPHS was common and the mortality rate was higher in the study area. The treatment modalities tested need further evaluation and confirmation.

Effects of high-dose parenteral vitamin D therapy on lipid profile and blood pressure in patients with diabetic nephropathy: A randomized double-blind clinical trial.

AIMS: Aim of this study was to determine the effect of high dose vitamin D given to patients with early diabetic renal disease on systolic and diastolic blood pressure, total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and high density lipoproteins (HDL) in a randomized controlled trial MATERIALS AND METHOD: Patients with early diabetic nephropathy were recruited. Selected patients were allocated to two groups by Block randomization method. Treatment group received 50,000 IU of vitamin D3 intramuscularly and the control group was given an equal volume of distilled water (0.25mL) monthly for six months. Blood and urine were collected at the baseline for biochemical analyses and blood pressure was measured. After six months all the measurements done at the baseline were repeated. RESULTS: Of 155 patients invited, 85 were randomly assigned to two groups. No significant differences were found between treatment and control groups at the baseline. Vitamin D therapy significantly reduced DBP, total cholesterol and LDL but the between group differences were not significant. There was an increase in HDL cholesterol level in the treatment group while there was no change in the control group Between groups difference was significant (P=<0.001). CONCLUSIONS: There was a significant improvement of serum HDL level with six months therapy of high dose vitamin D in patients with early diabetic nephropathy.

Treatment of glucocorticoid-induced low bone mineral density in children: a systematic review.

AIMS: The aim of this systematic review was to evaluate, critically, the treatment options used in the management of bone loss associated with glucocorticoid (GC) use among children. METHODS: We performed a systematic search using PubMed, Cochrane clinical trial registry, Clinicaltiral.gov and Ovid databases (1 March, 2013). The search resulted in 34 eligible retrievals. Of them, seven clinical trials that fulfilled the inclusion and exclusion criteria were selected by two authors. RESULTS: Four studies have compared the effectiveness of bisphosphonates in the treatment of GC-induced low bone mineral density (BMD) in children. Remaining studies were on menatretenone + alfacacidol versus alfacalcidol alone, calcium + vitamin D versus placebo and alfacalcidol versus menatetrenone. In the four studies, bisphosphonates have shown the ability either to improve BMD or prevent bone loss associated with GC use in children. However, alendronate either in oral or intravenous routes and oral pamidronate were the only bisphosphnates that have been studied in children. Vitamin K2 (menatetrenone) combined with alfacalcidol has also preserved BMD in children on long-term GC therapy. Calcium combined with alfacalcidol has also prevented bone loss, greater than menatetrenone. Calcitriol together with Calcium in conventional doses has retarded bone loss, although the combination could not completely prevent the process. CONCLUSIONS: Vitamin D derivatives such as calcitriol or alfacalcidol together with adequate calcium can be considered suitable treatment options to be started simultaneously when long-term GC therapy is needed in children. For children who have been on GCs or have already lost BMD, either oral pamidronate or alendronate in oral/intravenous routes can be considered based on the availability.

Effects of zinc and multimineral vitamin supplementation on glycemic and lipid control in adult diabetes.

AIMS: To evaluate the effects of zinc with or without other antioxidants on blood glucose, lipid profile, and serum creatinine in adult diabetics on long-term follow-up. MATERIALS AND METHODS: Patients (n = 96) were randomly allocated to three groups: group A (n = 29) was supplemented with oral zinc sulfate (22 mg/day) and multivitamin/mineral (zinc+MVM) preparation; group B (n = 31) was given the same preparation without zinc (MVM); and group C (n = 36) was given a matching placebo for a period of 4 months in a single-blinded study. Blood samples were taken at baseline and after 4 months of supplementation to assess blood glucose (fasting and postprandial) and glycosylated hemoglobin (Hb(A1C)%) and serum levels of zinc, creatinine, and lipids. RESULTS: The zinc+MVM group had a mean change of fasting blood sugar -0.33 mmol/L (standard error of the mean 0.21 mmol/L) and was significant (P = 0.05) when compared with the other two groups (mean change in the MVM group +0.19 (0.31) mmol/L and +0.43 (0.23) mmol/L in the control group, respectively). The Hb(A1C)% level reduced significantly, irrespective of the baseline level, in zinc+MVM-supplemented individuals. In the other two groups, the change of Hb(A1C)% level was not significant. Serum lipid levels reduced significantly in the zinc+MVM and MVM groups. CONCLUSIONS: Zinc+MVM supplementation showed beneficial effects in the metabolic control of adult diabetics in addition to elevating their serum zinc level. Zinc supplementation improved glycemic control measured by Hb(A1C)% and fasting and postprandial glucose. Furthermore, zinc supplementation lowered serum cholesterol and cholesterol/high-density lipoprotein ratio.

Long-term cereal-based nutritional supplementation improved the total spine bone mineral density amongst Sri Lankan preschool children: a randomized controlled study.

BACKGROUND: The Thriposha programme in Sri Lanka provides a combination of energy, protein and micronutrients as a 'ready-to-eat' cereal-based food. OBJECTIVE: To assess the effectiveness of calcium and vitamin D3 in the Thriposha on bone mineralization among preschool children aged 3-5 years. DESIGN: Subjects (n = 30) were fed with conventional Thriposha while the control group (n = 30) children were fed without mineral and vitamin premix (Corn-Soya-Blend - CSB) for a period of nine months. Dual-energy X-ray absorptiometry (DXA) of total spine was measured at the baseline and after the intervention. RESULTS: The mean baseline total spine BMD was 0.464 (0.050) g/cm2 in the interventional group and 0.453 (0.035) g/cm2 in the control group (p = 0.09). At the end of the study, the BMD levels were 0.487 (0.047) and 0.454 (0.031) g/cm2 (p < 0.001) respectively. CONCLUSION: Daily supplementation of cereal based food supplement over a period of nine months improved the total spine BMD.