Abstract
Post‐transcriptional gene silencing targets and degrades mRNA transcripts, silencing the expression of specific genes. RNA interference technology, using synthetic structurally well‐defined ...short double‐stranded RNA (small interfering RNA siRNA), has advanced rapidly in recent years. This introductory review describes the utility of siRNA, by exploring the underpinning biology, pharmacology, recent advances and clinical developments, alongside potential limitations and ongoing challenges. Mediated by the RNA‐induced silencing complex, siRNAs bind to specific complementary mRNAs, which are subsequently degraded. siRNA therapy offers advantages over other therapeutic approaches, including ability of specifically designed siRNAs to potentially target any mRNA and improved patient adherence through infrequent administration associated with a very long duration of action. Key pharmacokinetic and pharmacodynamic challenges include targeted administration, poor tissue penetration, nuclease inactivation, rapid renal elimination, immune activation and off‐target effects. These have been overcome by chemical modification of siRNA and/or by utilising a range of delivery systems, increasing bioavailability and stability to allow successful clinical translation. Patisiran (hereditary transthyretin‐mediated amyloidosis) was the first licensed siRNA, followed by givosiran (acute hepatic porphyria), lumasiran (primary hyperoxaluria type 1) and inclisiran (familial hypercholesterolaemia), which all use
N
‐acetylgalactosamine (GalNAc) linkage for effective liver‐directed delivery. Others are currently under development for indications varying from rare genetic diseases to common chronic non‐communicable diseases (hypertension, cancer). Technological advances are paving the way for broader clinical use. Ongoing challenges remain in targeting organs beyond the liver and reaching special sites (e.g., brain). By overcoming these barriers, siRNA therapy has the potential to substantially widen its therapeutic impact.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Diabetes mellitus has reached epidemic proportions worldwide. South Asians are known to have an increased predisposition for diabetes which has become an important health concern in the region. We ...discuss the prevalence of pre-diabetes and diabetes in South Asia and explore the differential risk factors reported.
Prevalence data were obtained by searching the Medline® database with; 'prediabetes' and 'diabetes mellitus' (MeSH major topic) and 'Epidemology/EP' (MeSH subheading). Search limits were articles in English, between 01/01/1980-31/12/2011, on human adults (≥19 years). The conjunction of the above results was narrowed down with country names.
The most recent reported prevalence of pre-diabetes:diabetes in regional countries were; Bangladesh-4.7%:8.5% (2004-2005;Rural), India-4.6%:12.5% (2007;Rural); Maldives-3.0%:3.7% (2004;National), Nepal-19.5%:9.5% (2007;Urban), Pakistan-3.0%:7.2% (2002;Rural), Sri Lanka-11.5%:10.3% (2005-2006;National). Urban populations demonstrated a higher prevalence of diabetes. An increasing trend in prevalence of diabetes was observed in urban/rural India and rural Sri Lanka. The diabetes epidemicity index decreased with the increasing prevalence of diabetes in respective countries. A high epidemicity index was seen in Sri Lanka (2005/2006-52.8%), while for other countries, the epidemicity index was comparatively low (rural India 2007-26.9%; urban India 2002/2005-31.3%, and urban Bangladesh-33.1%). Family history, urban residency, age, higher BMI, sedentary lifestyle, hypertension and waist-hip ratio were associated with an increased risks of diabetes.
A significant epidemic of diabetes is present in the South Asian region with a rapid increase in prevalence over the last two decades. Hence there is a need for urgent preventive and curative strategies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hypertension is a major contributor to the global non-communicable disease burden. Family history is an important non-modifiable risk factor for hypertension. The present study aims to describe the ...influence of family history (FH) on hypertension prevalence and associated metabolic risk factors in a large cohort of South Asian adults, from a nationally representative sample from Sri Lanka.
A cross-sectional survey among 5,000 Sri Lankan adults, evaluating FH at the levels of parents, grandparents, siblings and children. A binary logistic regression analysis was performed in all patients with 'presence of hypertension' as dichotomous dependent variable and using family history in parents, grandparents, siblings and children as binary independent variables. The adjusted odds ratio controlling for confounders (age, gender, body mass index, diabetes, hyperlipidemia and physical activity) are presented below.
In all adults the prevalence of hypertension was significantly higher in patients with a FH (29.3%, n = 572/1951) than those without (24.4%, n = 616/2530) (p < 0.001). Presence of a FH significantly increased the risk of hypertension (OR:1.29; 95% CI:1.13-1.47), obesity (OR:1.36; 95% CI: 1.27-1.45), central obesity (OR:1.30; 95% CI 1.22-1.40) and metabolic syndrome (OR:1.19; 95% CI: 1.08-1.30). In all adults presence of family history in parents (OR:1.28; 95% CI: 1.12-1.48), grandparents (OR:1.34; 95% CI: 1.20-1.50) and siblings (OR:1.27; 95% CI: 1.21-1.33) all were associated with significantly increased risk of developing hypertension.
Our results show that the prevalence of hypertension was significantly higher in those with a FH of hypertension. FH of hypertension was also associated with the prevalence of obesity, central obesity and metabolic syndrome. Individuals with a FH of hypertension form an easily identifiable group who may benefit from targeted interventions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) could be major risk factors for cardiovascular disease burden among high risk populations especially in South Asians. This ...systematic review and meta-analysis aimed to quantify the effects of coconut oil compared with other oils and fats on cardio-metabolic parameters.
PubMed, Scopus and Web of Science were systematically searched. The main outcomes included are lipid and glycemic parameters. Subgroup analyses were performed to evaluate individual comparisons of vegetable oils and animal fat with coconut oil. Data were pooled using random-effects meta-analysis.
Coconut oil consumption significantly increased TC by 15.42 mg/dL (95% CI, 8.96–21.88, p < 0.001), LDL-C by 10.14 mg/dL (95% CI, 4.44–15.84, p < 0.001) and high density lipoprorein cholesterol (HDL-C) by 2.61 mg/dL (95% CI, 0.95–4.26, p = 0.002), and significantly decreased glycosylated hemoglobin (HbA1c) by 0.39 mg/dL (95% CI, −0.50 to −0.27, p < 0.001) but, it had no effects on triglycerides (TG), (4.25 mg/dL; 95% CI, −0.49-8.99, p = 0.08) when compared with the control group. Sub-group analysis demonstrated that coconut oil significantly increased TC and LDL-C over corn, palm, soybean and safflower oils and not over olive oil. Compared with butter, coconut oil showed a better pattern in cardio-metabolic markers by significantly increasing HDL-C (4.38 mg/dL, 95% CI, 0.40 to 8.36, p = 0.03) and decreasing LDL-C (−14.90 mg/dL, 95% CI, −23.02 to-6.77, p < 0.001).
Our results suggest that coconut oil consumption results in significantly higher TC, LDL-C and HDL-C than other oils. Consumption of coconut oil can be one of the risk factors for CVDs in South Asians.
•Coconut oil significantly increased TC, LDL, HDL overall and sub-group analysis of corn, palm, soybean, safflower oils.•However, coconut oil raised HDL-C and lowered LDL-C in comparison to butter.•The results for anthropometric and glycemic control were inconclusive, though significant reduction in HbA1c was observed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hypocalcaemia is a rare, but reversible, cause of dilated cardiomyopathy causing heart failure. Several case reports have been reported on reversible cardiomyopathy secondary to hypocalcaemia.
We ...report a case of 54-year-old female Sri Lankan patient who presented with shortness of breath and was diagnosed with heart failure with reduced ejection fraction due to dilated cardiomyopathy. The etiology for dilated cardiomyopathy was identified as hypocalcemic cardiomyopathy, secondary to primary hypoparathyroidism, which was successfully treated with calcium and vitamin D replacement therapy.
This adds to literature of this rare cause of reversible cardiomyopathy secondary to hypocalcemia reported from the South Asian region of the world. This case highlights the impact of proper treatment improving the heart failure in patients with hypocalcemic cardiomyopathy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
The global aging population is expanding rapidly and many individuals have a particularly higher risk of malnutrition. Malnutrition can lead to impaired body function, morbidity, ...and mortality. Meeting nutritional requirements is a key strategy to minimize multiple debilitating adverse outcomes associated with malnutrition in the elderly.
Oral nutritional supplements (ONS) have been widely used as a dietary intervention for malnutrition in older adults. These supplements provide additional nutrients and calories to support nutritional requirements and have been shown to improve nutritional status, physical function, and quality of life in malnourished older adults.
Methods
This is an open-label, randomized controlled, parallel-group study including 50 institutionalized older adults (aged > 60 years) with malnutrition or at risk of malnutrition, living in a selected elderly care institution in Colombo, Sri Lanka. The aim is to assess improvement in healthy body weight gain and body composition in older adults with malnutrition at risk of malnutrition by using an ONS. Older adults will be screened for malnutrition using the Mini Nutrition Assessment (MNA) tool and eligible participants randomized using the simple random sampling technique to intervention and control groups (1:1 allocation ratio). The intervention group will consume 200 mL of ONS before bed continuously for 12 weeks. The primary outcome is the percentage who achieved at least 5% weight gain in the intervention group compared to the control group. Nutritional status (anthropometric, biochemical, clinical, and dietary), body composition (dual-energy X-ray absorptiometry), frailty, functional capacity (hand grip strength, knee extension, and Barthel index) cognitive status (Montreal Cognitive Assessment), and physical activity will be assessed as secondary outcomes at baseline and at the end of the 12-week intervention. Some measurements (anthropometry, dietary, and functional assessments) will also be performed at the end of the 4th week. Data will be analyzed using SPSS V-23.
Discussion
This study will determine whether the use of an ONS is effective in promoting healthy weight gain in older adults with malnutrition or at risk of malnutrition. In addition, investigating the impact of an ONS on multiple outcomes via clinical, nutritional, functional, and cognitive function will provide a more comprehensive understanding of the potential benefits of these supplements.
Trial registration
Sri Lanka Clinical Trail Registry SLCTR/2022/021. Oct. 6, 2022.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
During recent years several studies have investigated the impact of different dietary oils on body weight. They have shown differential positive and negative effects on anthropometry. We investigated ...the effects of palm and coconut oils on body weight and other anthropometric parameters, considering their importance as a primary source of saturated fat, controlling for other confounding variable such as total energy intake.
The study was conducted as a sequential feeding clinical trial with 40 healthy men and women divided into two feeding periods of initial palm oil (8 weeks) and subsequent coconut oil (8 weeks), with a 16-week washout period in between. Each participant received a pre-determined volume of each oil, which were integrated into their routine main meals and snacks during the respective study periods. Changes in body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were evaluated. Physical activity levels and dietary intake were also evaluated as potential confounding factors.
Thirty-seven participants completed both oil treatment periods. The mean (± SD) age of the participants was 39 (± 13.1) years. There were no significant differences in any of the anthropometric parameters between the initial point of feeding coconut oil and the initial point of feeding palm oil. Following both oil treatment phases, no significant changes in the subjects' body weight, BMI, or other anthropometric measurements (WC, HC, and WHR) were observed.
Neither coconut oil nor palm oil significantly changed anthropometry-related cardiovascular risk factors such as body weight, BMI, WC, HC, and WHR.
Sri Lankan Clinical Trial Registry: SLCTR/2019/034 on 4th October 2019 ( https://slctr.lk/trials/slctr-2019-034 ).
Obesity is defined as an abnormal/excessive accumulation of body fat, associated with health consequences. Although overall obesity does confer a significant threat to the health of individuals, the ...distribution of body fat, especially abdominal/central obesity is of greater importance. For practical reasons, proxy anthropometric measurements have been developed to identify central obesity, however, major limitations are noted in these traditional measurements. The present study aims to evaluate the literature, to identify and describe non-traditional anthropometric measurements of overweight and obesity in children. The current systematic review was conducted in accordance with the PRISMA guidelines, and the search was undertaken in the PubMed
database, using MeSH (Medical Subject Headings) terms. Data extracted from each study were: (a) details of the study, (b) anthropometric parameter(s) evaluated in the study and its details, (c) study methods, (d) objectives of the study and/or comparisons, and (e) main findings/conclusions of the study. The search yielded a total of 3697 articles, of which 31 studies were deemed eligible to be included. The literature search identified 13 non-traditional anthropometric parameters. Data on non-traditional anthropometric parameters were derived from 24 countries. Majority were descriptive cross-sectional studies (n = 29), while sample size varied from 65 to 23,043. Non-traditional anthropometric parameters showed variable correlation with obesity and/or related metabolic risk factors. Some parameters involved complex calculations, while others were based on a single anthropometric measurement or derived from traditional measures. Most studies lacked comparison with a 'gold standard' assessment of body fat, hence further research is required to determine their accuracy and precision.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Abstract
Introduction
Availability of essential medicines that meet the expected quality standards, in appropriate dosage forms at affordable prices is a fundamental prerequisite to fulfill ...healthcare needs of given a population. This study assessed available products, prices and affordability of essential medicines (EM) in community pharmacies in Sri Lanka with comparison of registration status from the National Medicines Regulatory Authority(NMRA).
Methods
A cross-sectional island-wide survey of 80 pharmacies was conducted according to World Health Organization and Health Action International Manual (WHO/HAI). Hundred medicines were selected from the global core list(n = 14), regional core list(n = 16) and the Sri Lanka Essential Medicine List (SL-EML) (n = 70) based on healthcare needs. Number of registered products in 2015 and 2021 were compared.
Findings
Average availability was 85.4%(± 12.31) and availability was lowest in the Northern province (69.38 ± 21.18%)(p = 0.008). Availability between the state owned, franchise and privately owned pharmacies was not significantly different (p > 0.05). 89.4% medicines were affordable except for amiodarone, hydroxychloroquine, sitagliptin, soluble insulin, isophane insulin, losartan, levodopa carbidopa combination, clonazepam and ceftriaxone. The median price ratio (MPR) of 33.7% of medicines was less than 1 and MPR of 37.1% originator brands (OB) was over 3. Median number of generic brands in the market was 8(range 2–44), 9% of medicines had 20 or more products in the market and 72.7% medicines had more products available than the number registered in 2015. The average number of registered products were similar in 2015 (8.27) and 2021(7.59) (p = 0.15).
Conclusion
The overall availability of EMs in Sri Lanka was high in all categories of community pharmacies. Medicines were largely affordable and reasonably priced in 2015, although OBs were generally more expensive. Majority of medicines had more products in the market than the number of registered products.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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