Real World Evidence of Bempedoic Acid on Efficacy and Safety in Patients with Uncontrolled LDL-c and at High Risk of CVD

Background and Objective: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality worldwide, with high-risk patients requiring effective management to reduce their risk of cardiovascular events. Bempedoic acid is a novel therapeutic agent recently approved as an add-on therapy to statins in patients with uncontrolled LDL-c. Bempedoic acid inhibits cholesterol synthesis in the liver, which ultimately reduces the risk of cardiovascular events. Therefore, the present study aims to assess the efficacy and safety of bempedoic acid in patients with uncontrolled LDL-c (Previously on moderate or high-intensity statins) with a high risk of CVD in real-world settings. Methods: This is a multicenter, retrospective, observational study on the data of high-risk-CVD patients collected from Bempedoic Acid on Efficacy and Safety in patients (BEST) Registry. The clinical data of 140 patients who were already on statin therapy and were receiving Bempedoic acid at a dose of 180 mg, along with measurements of the level of LDL-c, HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, serum creatinine was taken into consideration. The primary outcome includes a change in LDL-c level, and secondary outcomes involve a change in the level of HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, and serum creatinine at week 12 and 24. Adverse events were reported at both time points. Results: A total of 140 patients were included in the present study with a mean age of 51.8 ± 9.2 years and had primary confirmed diagnosis of dyslipidemia with uncontrolled LDL-c. The mean levels of LDL-c decreased from the mean baseline value of 142.67 ± 46.49 mg/dL, to 106.78 ±33.92 mg/d; a statistically significant reduction by 23.23% (p < 0.01) at week 12. Similarly, at week 24, the mean LDL-c value reduced to 90.39 ± 38.89 mg/dL. A 33.38 % decrease was observed (p < 0.01). Other parameters such as non-HDL, FPG, PPPG, AST and serum creatinine also showed statistically significant reduction at week 12 and week 24. Conclusion: The present study demonstrates that bempedoic acid is an effective add-on medication in lowering LDL-c levels in high-risk CVD patients with uncontrolled LDL-c.

Comparison of Pain Scores and Rescue Analgesia Required Amongst Subjects Receiving Ropivacaine and Clonidine versus Ropivacaine Alone: An Institutional Based Study

Background: Pain is an individual and subjective experiencewhich can be modulated by several physiological,psychological and environmental factors such as previousexperience, fear, anxiety and cultural factors .The usual trendis to prescribe an opioid or a NSAID for postoperativeanalgesia. NSAIDs also have certain side effects likehemostasis alteration, renal dysfunction, gastrointestinalhemorrhage etc. TAP block is a local anaesthetic block used toprovide analgesia to the anterior and lateral abdominal wall.The present study was conducted to compare pain scores andrescue analgesia required amongst subjects receivingropivacaine and clonidine versus ropivacaine alone.Materials and Methods: A prospective, randomized, doubleblinded control trial undertaking 70 patients was conductedbetween September 2014 to March 2016 at the Department ofAnesthesiology, Northern Railway Central Hospital, New Delhi.Patients undergoing infra umbilical surgery under subarachnoidblock were included hysterectomy, caesarean section,cystolithotomy and bilateral inguinal hernias. All investigatorsinvolved in study were unaware of envelope details throughoutstudy period. Group C was given 20 ml of 0.2% ropivacainewith 25 microgram clonidine on each side, total of 40 ml of0.2% ropivacaine with 50 mcg clonidine. Group R was given 20ml of 0.2% ropivacaine on each side, total 40 ml of 0.2%ropivacaine. The postoperative pain at 1 hr, 3 hr, 6 hr, 9 hr, 12hr,18 hr, 24 hr by VAS score were noted and the totalpostoperative rescue analgesic dose in two groups. All the datathus obtained was arranged in a tabulated form and analyzedusing SPSS software.Results: Total males included in the study were 17 andfemales were 53. There was significant difference in group Cand group R in VAS score. It was consistently lower in group Cwhen compared with group R for first 12 hours. Total amount ofrescue analgesia used in the two groups was significantlydifferent. Total mean 150 mg of diclofenac sodium was given topatients in group C.Conclusion: USG-TAP block when used with adjuvant a2agonist (clonidine) along with local anaesthetic (ropivacaine)leads to prolongation of analgesic effect, lower vas scores andreduced requirement of rescue analgesic.

Physicochemical and antioxidant properties of kiwifruit as a function of cultivar and fruit harvested month

The present study was carried out to find the effect of fruit harvesting stage (October, November and December) on the physicochemical and antioxidant properties in five kiwi cultivars (Abbot, Bruno, Allison, Hayward, Monty). Results showed that soluble solid content (SSC) and pH increased while ascorbic acid (Vit C), titrated acidity (TAD) and SSC/TAD decreased in all the cultivars with delay in harvesting. Total polyphenols (TP) were decreased while total flavonoids (TF) increased in all tested cultivars with delay in harvesting. The highest concentration of TP (2.02 mg gallic acid equivalent/g fresh weight) and TF (51.12 mg catechin equivalent/100g FW) were found in cultivar 'Allison' in the month of October and December, respectively. Antioxidant activities (AA) were genotype depended and no trend was observed with month of harvesting. Principal component analysis (PCA) showed strong correlation between Vit C, TP and antioxidant activities. Two major clusters were computed using agglomerative hierarchical clustering (AHC). All the studied important traits may be used in the breeding programmes to increase the variability for different physiochemical and antioxidative characteristics and to make suitable selections that could be acceptable to consumers.

An experimental study on the effect of isoniazid on the efficacy, plasma concentration and toxicity of paracetamol in Albino rats.

Background: Paracetamol is used for symptomatic treatment of fever and pain with isoniazid and other anti-tubercular drugs in patients of tuberculosis. Literature has conflicting data regarding their interaction. Some studies show that isoniazid increases oxidative metabolism of paracetamol whereas some other suggest that isoniazid has an inhibitory effect. The present study was conducted to find out the possible interaction between paracetamol and isoniazid. Methods: The study was undertaken on Wistar strain of Albino rats. Group I and Group II animals were treated with paracetamol (500 mg/kg) and the combination of paracetamol (500 mg/kg) and isoniazid (30 mg/kg) respectively for 2 months. Blood samples were taken before and during the study for biochemical and histopathological studies of liver and renal functions and plasma paracetamol concentration was also evaluated. Results: Isoniazid decreased the plasma paracetamol concentration without affecting its analgesic activity. However, the hepatotoxic and nephrotoxic effects of paracetamol were found to be further aggravated by isoniazid co-administration. Conclusion: Isoniazid potentiates the hepatotoxic and nephrotoxic effects of paracetamol possibly due to hepatic enzyme induction by isoniazid.

Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats.

Citrinin is the one of the well-known mycotoxins, which is possibly spread all over the world. The graded doses of citrinin (1, 3 and 5 ppm CIT in feed) in female Wistar rats 10 weeks prior to mating, during mating and during organogenesis resulted in resorptions and post implantation losses, decreased fetal body weights and crown-rump lengths in fetuses of all groups. Various developmental anomalies recorded in fetuses of treated rats included gross (wrist drop, curled tail, stretched forelimb, subcutaneous haematoma), skeletal (incomplete ossification of skull bones, incomplete fusion of vertebral bodies, complete and partial agenesis of sternaebrae, metacarpals, metatarsals and phalanges, fused ribs and swing out ribs) and visceral (internal and external hydrocephalus, cerebellar hypoplasia, microphthalmia, roundening of heart, contracted kidneys, dilated renal pelvis and cryptorchid testes). The results suggest that CIT has adverse effects on fetal development which may be due to the longer bioavailability of citrinin in the animals.

Spinosad: A Newer Anti-Lice Drug.

Head lice infestation is a common and highly contagious condition caused by pediculus humanus capitis. Therapy for head lice infestation has been traditionally combing out the live lice and the unhatched eggs (nits) by a fine toothed comb along with topical chemical treatments. Emergence of resistance to these therapies compromises their effectiveness. As a result, the search for newer agents has been a clinical necessity. Recently, spinosad, a newer anti-lice drug, has been approved by US FDA as 0.9% topical suspension. Spinosad provides a useful alternative for children above 4 years of age suffering from head lice infestation.

Beneficiary level factors influencing Janani Suraksha Yojana utilization in urban slum population of trans-Yamuna area of Delhi.

Background & objectives: Janani Suraksha Yojana (JSY), a conditional cash transfer scheme introduced to improve the institutional delivery rates and thereby reduce the maternal and infant mortality was implemented in all States and Union Territories of India from 2007. The present study was carried out to identify the beneficiary level factors of utilization of JSY scheme in urban slums and resettlement colonies of trans-Yamuna area of Delhi. Methods: A cross-sectional community based survey was done of mothers of infants in the selected areas of the two districts by stratified random sampling on a population proportionate basis. Socio-demographic factors, antenatal services availed and distance of nearest health facility were studied. Outcome variable, a beneficiary, was a woman who had ever interacted with the ASHA of her area during the antenatal period of previous pregnancy and had child birth in an institution. Descriptive tables were drawn; univariate analysis followed by multiple logistic regression was applied for identifying the predictors for availing the benefits. Results: Of the 469 mothers interviewed, 333 (71%) had institutional delivery, 128 (27.3%) had benefited from JSY scheme and 68 (14.5%) had received cash benefits of JSY. Belonging to Hindu religion and having had more than 6 antenatal check ups were the significant predictors of availing the benefits of JSY. Conclusion: There is a need to improve the awareness among urban slum population about the utilization of JSY scheme. Targeting difficult to access areas with special measures and encouraging more antenatal visits were essential, prerequisites to improve the impact of JSY.

Diversity of Arbuscular Mycorrhizal Fungi in Oak-Pine Forests and Agricultural Land Prevalent in the Kumaon Himalayan Hills, Uttarakhand, India.

The diversity and abundance of arbuscular mycorrhizal fungi (AMF) was assessed in the Kumaon Himalayan foothills. Four typical ecosystems were selected in the Sat-Tal area located in the Nainital, district in Uttarakhand, India, representing vegetation change due to human settlement and selective logging of native oak. Besides a natural oak forest, a mixed pine-oak forest, a pure pine stand and an arable field were sampled. The latter was cropped with black gram (Vigna mungo L. Hepper) and maize (Zea mays L.) during the rainy season from June to September and rotated with wheat (Triticum aestivum L.) during winter for the last 10 years. Only cow dung compost used for fertilization. The highest AMF spore abundance throughout the year was recorded in soil samples from the pine-oak mixed forest, followed by the pine and oak forests and the agricultural field. At all sites, the lowest spore abundance was recorded at the end of the winter season in March, and the highest in October after the rainy season. Whereas in October, Glomus claroideum, Acaulospora scrobiculata and A. spinosa were found at all sites, in March it was only G. intraradices which occurred everywhere. The highest AMF spore morphotype richness was recorded in samples from the oak forest. In AMF-trap cultures set up with field soil inocula, the dominant species recovered were G. intraradices, G. etunicatum and A. scrobiculata. As compared to the field samples, trap culturing of one year enhanced spore abundance but entailed a loss of AMF richness. The study revealed differences in AMF community composition and structure among sites characterized by different land use systems.

Lytic bacteriophages specific to Flavobacterium columnare rescue catfish, Clarias batrachus (Linn.) from columnaris disease.

This investigation was aimed to find out appropriate strategy against antibiotic resistant bacterial fish pathogen, F. columnare. This pathogen was found persistently associated with fishes causing columnaris disease and ensuing mass mortality in hatchery and culture system of Sub - Himalayan region. Nine lytic F. columnare phages (FCP1 – FCP9) specific to its fifteen isolates were isolated from the water and bottom sediments of various geo-climatic regions of North India. The F. columnare phage FCP1 (made of hexagonal head and non contractile long tail belonging to family Podovariedae, a member of DNA virus) exhibited broader host range to lyse 9 out of 15 isolates of F. columnare. Therapeutic ability of FCP1 phage was assessed in C. batrachus inoculated intramuscularly (im) with virulent bacterial isolate FC8 and post inoculated (PI) with FCP1phage (@ 108 : 106 :: cfu : pfu) through intramuscular (im), immersion (bath) and oral (phage impregnated feed) treatment. Significant (p<0.001) reduction (less than 10-3 cfu ml-1) in host bacterium in the sera, gill, liver and kidney of challenged fishes was noted after 6 hr of phage treatment. Quantum of phage played a significant role in bringing down bacterial population as in the sera of dose 1 (@ 4.55 X 106 pfu ml-1) and dose 2 (@ 9.15 X 106 pfu ml-1) treated fishes mean log10 cfu value reduced by 3 logs (58.39%) and 5 logs (73.77%) at 96 hr, respectively. Phage treatment led to disappearance of gross symptoms, negative bacteriological test, detectable phage and 100% survival in experimentally infected C. batrachus. Result of this study provides evidence of profound lytic impact of FCP1 phage and represents its interesting therapeutic importance against antibiotic resistant F. columnare.

Prevalence of stress among resident doctors working in Medical Colleges of Delhi.

The present cross-sectional study was conducted from November 2007 to December 2008 in four medical colleges and associated hospitals of Delhi. Study subjects comprised 930 resident doctors. The overall prevalence of stress was found to be 32.8% in resident doctors from all colleges. Out of 930 resident doctors, 165 (17.7%) had mild stress, 113 (12.2%) had moderate stress, and 27 (2.9%) were severely stressed. Important reasons of stress as perceived by the study subjects included long duty hours, departmental academic activities, financial constraints, family and emotional problems in the decreasing order of preference. Important factors significantly associated with stress-included existence of children, year of residency, type of department, and presence or absence of job satisfaction, having close friends, spending time with family/friends, and place of graduation. In the multivariate model, year of residency, giving time to family and or friends, having close friends during residency, job satisfaction, and state of graduation came out as predictors of stress.

Impact of NGO run mid day meal program on nutrition status and growth of primary school children.

Objective. To study the impact of wholesome mid day meal (MDM) program run by an NGO on the growth of the primary school students in rural area of Mathura district. Methods. This intervention study involved children enrolled in Government run rural primary schools in Mathura district in Uttar Pradesh from March 06 through August 07. A wholesome, nutritionally balanced MDM provided by an NGO for the students in the 6 primary schools was selected as intervention group. Control group consisted of children in 8 schools which received locally prepared MDM by village panchayats. Height, weight, change in height/month, change in weight/month, prevalence of protein-energy malnutrition and prevalence of signs of vitamin deficiencies, were measured. Results. Food was provided for 221 days in one year. Within group and between groups repetitive measures were compared using generalized estimating equation (GEE). Within both intervention and control groups height and weight had significantly increased (p < 0.05), while there was no significant difference between the groups. There was no change in prevalence of malnutrition within either of the groups. Reduction in vitamin A deficiency signs was 38% more in intervention group (p < 0.001). Prevalence of Vitamin D deficiency reduced by 50% more in intervention group. No such differences between groups were observed for vitamin B complex and vitamin C. Conclusions. MDM provided by the NGO has no better impact on growth of the primary school children, however, it reduced prevalence of vitamin deficiency significantly in comparison to the MDM run by Village Panchayats.

Nuclear factor kappa-B and histopathology of chronic gastritis.

Background: Studies suggest that nuclear factor kappa-B (NFκB) activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. Materials and Methods: This study examines the expression and activity of NFκB in situ in antral biopsies of 42 consecutive patients with immunohistochemical techniques. Results: NFκB was highly expressed in the gastric epithelial cells. The number of cells showing activated NFκB correlated with the activity of gastritis (P < 0.05), a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. There was also a strong inverse association with the presence and grade of atrophy. Conclusion: This correlation is direct evidence of the importance of NFκB dependent signal transduction for neutrophil influx in gastritis. The role of NFκB appears to be only in the initial stages of gastritis, there is no role for the molecule in the development of chronic inflammation or atrophy.

Aggressive angiomyxoma of the jejunum: a rare cause of obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding accounts for nearly 5% of all gastrointestinal haemorrhage and is frequently due to a lesion in the small bowel. We report the case of a male patient with obscure overt gastrointestinal bleed in whom repeated upper gastrointestinal endoscopy, colonoscopy, computed tomography scanning and exploratory laparotomy showed no specific pathology. However, on capsule endoscopy done subsequently, a small polyp in the jejunum was located and resected. Histology revealed an aggressive angiomyxoma. This type of small bowel lesion has not been reported in the literature before.

DNA profiling: Social, legal, or biological parentage.

DNA profiling in forensic casework is based on comparison of the results of biological evidence with direct reference samples of the individual concerned or with indirect references of his close blood relatives. The selection of reference samples for analysis is crucial to the success of a case; it not only depends on the authenticity of the reference samples, but also on the authenticity of the biological relation of the donors with the person in question. There are situations when the social or legal relationship is not the biological one and there is a need to educate investigating officers, forensic analysts, and the judiciary about the associated problems.

Trichrome staining for detection of intestinal protozoa a better screening method.

Intestinal protozoal infections are common in our country because of poor hygiene and tropical conditions. The efficacy of trichrome staining to screen stool smear was compared with commonly used methods i.e. concentrated iodine mount and direct wet mount to test its better effectiveness. All Stool samples were first examined by routine methods i.e. direct wet mount and iodine staining. A portion of stool sample was also inoculated in vial containing polyvinyl alcohol (PVA) fixative. From PVA preserved samples, slides were prepared and stained by modified wheately's trichrome method. The results of both methods were compared and relative accuracy was calculated. 1054 stool specimens were examined and 259 parasites detected, of which 20.7% were protozoa and 3.7% helminthde. Trichrome staining detected 19.1% protozoa while routine methods detected 12.9% protozoa. For identification of protozoa, accuracy was 91.8% in favor trichrome staining and 61.8% by wet mount and iodine staining. Trichrome stained smear alone can be used as screening method in those geographic areas where protozoa infections are common.