PURPOSE: Although the use of steroids in the management of COVID-19 has been addressed by a few systematic review and meta-analysis, however, they also used data from “SARS-CoV” and “MERS-CoV.” Again, most of these studies addressed only one severity category of patients or addressed only one efficacy endpoint (mortality). In this context, we conducted this meta-analysis to evaluate the efficacy and safety of steroid therapy among all severity categories of patients with COVID-19 (mild to moderate and severe to critical category) in terms of “mortality,” “requirement of mechanical ventilation,” “requirement of ICU” and clinical cure parameters. METHODS: 11 databases were screened. Only randomized controlled trials (RCTs) or high quality (on the basis of risk of bias analysis) comparative-observational studies were included in the analysis. RevMan5.3 was used for the meta-analysis. RESULTS: A total of 15 studies (3 RCT and 12 comparative-observational studies) were included. In the mechanically-ventilated COVID-19 population, treatment with dexamethasone showed significant protection against mortality (single study). Among severe and critically ill combined population, steroid administration was significantly associated with lowered mortality (risk ratio [RR] 0.83 [0.76–0.910]), lowered requirement of mechanical ventilation (RR 0.59 [0.51–0.69]), decreased requirement of intensive care unit (ICU) (RR 0.62 [0.45–0.86]), lowered length of ICU stay (single-study) and decreased duration of mechanical ventilation (two-studies). In mild to moderate population, steroid treatment was associated with a higher “duration of hospital stay,” while no difference was seen in other domains. In patients at risk of progression to “acute respiratory distress syndrome,” steroid administration was associated with “reduced requirement of mechanical ventilation” (single-study). CONCLUSION: This study guides the use of steroid across patients with different severity categories of COVID-19. Among mechanically ventilated patients, steroid therapy may be beneficial in terms of reduced mortality. Among “severe and critical” patients; steroid therapy was associated with lowered mortality, decreased requirement of mechanical ventilation, and ICU. However, no benefit was observed in “mild to moderate” population. To conclude, among properly selected patient populations (based-upon clinical severity and biomarker status), steroid administration may prove beneficial in patients with COVID-19.

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There are a limited number of studies on postoverdose clinical findings of mirtazapine in the literature. Our case presented an unlikely junctional rhythm, which we have not seen in the previous studies, in a patient who had bradycardia and hypotension following mirtazapine intake. A 37-year old male was admitted to the emergency department (ED) after his suicide attempt with 300 mg PO of mirtazapine tablets. He took the drug 2 h prior to his ED visit. He did not have any complaints after the mirtazapine intake. His complete physical examination and electrocardiography (ECG) revealed no pathological findings. He was observed in the ED. The results were in the normal range in his blood test and he has 0 mg/dl of blood ethanol. He experienced dizziness after 5 h and 30 min. The blood pressure was 60/30 mmHg. The heart rate was 34 beats/min. The simultaneous ECG showed junctional bradycardia. 0.5 mg atropine IV was given two times at intervals. Norepinephrine infusion was initiated after normal saline therapy. Forty-five minutes later, he did not have any clinically significant complaint. There are no pathological findings in his follow-up ECG and physical examination. He was discharged of his own accord 10 h after his ED admission. His initial mirtazapine level was 145 ng/ml when he came to the ED. Mirtazapine was known to have a safe cardiac profile both for regular dose and overdose. However, physicians should consider that it might induce a life-threatening bradyarrhythmia.

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OBJECTIVES: The objective was to evaluate the efficacy of antiviral agent valacyclovir compared with famciclovir in the treatment of herpes zoster. MATERIALS AND METHODS: A comparative study was conducted over a period of 1 year. Data relevant to the study were collected from 60 patients, with active herpes zoster presenting to the outpatient department within 72 hr of the first occurrence of zoster rash. They were divided in to two groups of 30 patients each. The first group of patients received valacyclovir tablet 1000 mg thrice daily, whereas those in the second group were given famciclovir tablet 500 mg thrice daily. Both the drugs were given for 7 days. Periodic follow-up till 29^th day was done for assessment of the effects of given drugs. RESULTS: Significant decrease was observed on comparison of pain scores between the two groups using the visual analog scale, with the drug valacyclovir, than in the famciclovir group at day 29. Furthermore, valacyclovir treatment accelerated the resolution of zoster associated pain in more number of patients compared with famciclovir. CONCLUSION: Oral valacyclovir administered during acute zoster infection for a period of 7 days offers significant benefit compared to famciclovir by providing a well tolerated and greater resolution of pain while maintaining the favorable safety profile, making valacyclovir more efficacious and a better drug in management of Herpes Zoster in comparison to famciclovir.

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INTRODUCTION: Vernal conjunctivitis comprises 0.5% of allergic eye diseases. The study is intended to collate the effectiveness of drugs by observing the reduction in signs and symptoms. OBJECTIVES: The objective of the study is to evaluate the effectiveness and safety of olopatadine 0.1% ophthalmic drops with bepotastine besilate 1.5% ophthalmic drops in patients with vernal keratoconjunctivitis (VKC). MATERIALS AND METHODS: A randomized, open-label, comparative study conducted in Sarojini Devi Eye Hospital, Telangana. The study included 50 patients diagnosed with VKC, of which Group A and Group B were given olopatadine 0.1% ophthalmic drops and bepotastine besilate 1.5% ophthalmic drops, respectively, twice a day for 8 weeks. The reduction in signs and symptoms in both groups was compared. The observations and results were tabulated accordingly, and data were analyzed using the SPSS. The unpaired t-test is used as the test of significance in between two groups. P value is statistically significant when it is less than 0.05. RESULTS: Overall, 50 cases were included in the study, 72% of total patients were in the age group of 5–10 years, and 28% were in the age group of 11–15 years. There were 39 males and 11 females. After 8 weeks of follow-up, the mean reduction in the scoring of symptoms and signs provided better and quicker relief of watering, ocular discomfort, and conjunctival hyperemia with bepotastine 1.5% eye drops. Olopatadine 0.1% eye drops provided faster improvement in papillary hypertrophy. Both drugs were equally effective in reducing itching. Laboratory findings of absolute eosinophil count had no statistical significance in between the two groups. CONCLUSIONS: In this study, based on the evaluation of therapeutic performance, bepotastine eye drops proved quicker relief of symptoms and signs compared to olopatadine eye drops but was not statistically significant which would prove beneficial for the patients.

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During the last two decades, the development in drug discovery is slackening due to drug withdrawal from the market or reported to have postmarket safety events. The vital organ toxicities, especially cardiotoxicity, hepatotoxicity, pulmonary toxicity, and neurotoxicity are the major concerns for high drug attrition rates. The pharmaceutical industry is looking for high throughput, high content analysis based novel assays that would be fast, efficient, reproducible, and cost-effective; would address toxicity, the safety of lead molecules, and complement currently used cell-based assays in preclinical testing. The use of zebrafish, a vertebrate screening model, for preclinical testing is increasing owing to the number of advantages and striking similarities with the mammal. The zebrafish embryo development is fast and all vital organs such as the heart, liver, brain, pancreas, and kidneys in zebrafish are functional within 96–120hpf. The maintenance cost of zebrafish is reasonably low as compared to mammalian systems. Due to these features, zebrafish has arisen as a potential experimental screening model in lead identification and validation in the drug efficacy, toxicity, and safety evaluation. Numbers of drugs and chemicals are screened using zebrafish embryos, and results were found to show 100% concordance with mammalian screening data. The application of zebrafish, being a whole-organism screening model, would show a significant reduction in the cost and time required in the drug development process. The present challenge includes complete automation of the zebrafish screening model, i.e., from sorting, imaging of embryos to data analysis to accelerate the therapeutic target identification, and validation process.

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CONTEXT: The acquisition of antibiotic without a prescription by the general population is a typical practice found in community pharmacies across India, which is a notable contributor of antimicrobial resistance. According to the present regulation in India, sale of certain antimicrobials included in schedule H1 without prescription is unlawful. In this contest, a program was organized by the Drug Control Administration, Government of Andhra Pradesh, to educate pharmacists regarding schedule H1. AIMS: The aim of our study is to assess the impact of the program on the rate of antibiotics dispensed at community pharmacies. SETTINGS AND DESIGN: A cross-sectional study was designed to investigate the nonprescription sale of antibiotics, from September to December 2018 through 200 community pharmacies located in and around Guntur city located in the state of Andhra Pradesh in India. SUBJECTS AND METHODS: A simulated client methodology was used in this study. A total of 3 female actors including an author of this present study are prior trained to present a standardized simulation of clinical conditions (sore throat, urinary tract infection, cold, and fever) to the pharmacist at the community pharmacies. STATISTICAL ANALYSIS USED: Microsoft excel sheet was used for data analysis. RESULTS: The simulated patients successfully obtained antibiotic from 78% pharmacies with the highest rate of urinary tract infection when compared to other conditions. Pharmacists who objected to dispense antibiotics (22%) are found in developed locations in the city and appeared well qualified. CONCLUSIONS: The present study revealed that the antibiotics are continued to be sold without prescription even after the education program on schedule H1. The deregulation of the act is definitely the problem to be addressed by the government.

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Chronic iron overload in beta-thalassemia patients after continuous blood transfusions has caused notable morbidity and mortality in these patients. The once-a-day oral iron chelator, deferasirox has established efficacy and bearable safety in adults and pediatric thalassemia patients. It is now extensively used for the management of transfusional hemosiderosis. However, a number of studies have revealed a few patients continued to be none respondent or intolerant toward the once-a-day regimen of deferasirox even after the administration of maximum dose recommended by the World Health Organization. In the literature, there were three studies showing the boon of twice in a day dosing of deferasirox among transfusional-dependent beta thalassemia patients. Therefore, a nonsystematic review was conducted on above three studies to ascertain the enhanced effectiveness and tolerability of twice per day regimen of deferasirox with the same total dose as that of once daily regimen of deferasirox in unresponsive or intolerant transfusion-dependent beta-thalassemia (TDT) patients. All the above studies concluded that the twice per day regimen of deferasirox was more efficacious and tolerable among TDT patients when compared to the once-a-day regimen with the same total daily dose. Although there was a significant good results from these studies, there is a need to conduct either muticenter study or randomized control study in a larger number of patients for the better confirmation of the results as all the above studies were conducted in the small number of TDT patients.

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OBJECTIVES: The objective of this study is to analyze the antiproliferative activity of Acacia nilotica (L.) leaf ethanolic extract against cancer KB cells and to determine the mode of cancer cytotoxicity. MATERIALS AND METHODS: In this study, high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis were done to confirm the presence of ethyl gallate as a major bioactive phenolic in the leaf ethanolic extract of A. nilotica, further dose-dependent (0–120 μg/mL) antiproliferative effect was investigated in human carcinoma cell line KB. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, reactive oxygen species, mitochondrial membrane potential loss, DNA damage, and apoptosis were evaluated. RESULTS: A. nilotica leaf ethanolic extract (ANLEE) showed effective concentration (EC₅₀) of 40 μg/mL. Interference of growth was significantly (P < 0.05) high in KB cells treated with ANLEE when compared to untreated control, but less when compared to the reference drug paclitaxel. In addition, the in vivo acute toxicity study demonstrated the safe limit of administration of 2000 mg/kg body weight ANLEE by the histological analysis in rats. The results from the present study indicate that mitochondria and DNA of KB cells are severely affected leading to apoptosis. CONCLUSIONS: ANLEE is a prospective source for cancer therapy and therefore should be highlighted to explore on its wide range of safety in rats and efficacy against human carcinoma cell line KB.

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PURPOSE: To identify the possibility of modulating retinal glucose transporters in diabetic conditions to prevent retinal complications of diabetic retinopathy. MATERIALS AND METHODS: In silico and in vitro binding assays were performed to assess the effect of genistein and positive controls (pioglitazone and estradiol) on nuclear receptor estrogen receptor beta and peroxisome proliferator-activated receptor gamma (PPARγ). In vivo effects of compounds were tested on diabetic rats. Structural and functional analysis of retina was performed at 28^th day followed by gene expression analysis of glucose transporters and nuclear receptors. Pioglitazone and genistein levels were analyzed by liquid chromatography with tandem mass spectrometry. RESULTS: Genistein showed equi-affinity toward PPARγ in in silico experiments contrary to in vitro findings. In multidose study, their therapeutic effects were observed by analyzing the retinal function. Retinal gene expression studies revealed that both test agents significantly up regulated PPARγ, GLUT4, and down regulated GLUT1. Genistein showed significant up regulation of GLUT4 and down regulation of GLUT1 as compared to PGZ which has been well correlated with the Electroretinography (ERG) outcome. CONCLUSION: This study showed the possibility of selective upregulation of GLUT4 (independent of PPARγ activation) in the retina of diabetic rats using genistein. Selective modulation of retinal glucose transporters as therapeutic target in ocular diabetic complications can be possibly explored.

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OBJECTIVES: Mother-to-child transmission of HIV has witnessed a significant reduction due to effective antiretroviral therapy (ART). Efavirenz has been introduced as a part of ART since last few years in the national Prevention of Parent to Child Transmission (PPTCT) program for pregnant women living with HIV. However, data related to adverse pregnancy outcomes associated with efavirenz-based ART are limited in the Indian scenario. The present study evaluated pregnancy outcomes in HIV-infected pregnant women who were given efavirenz-based ART during pregnancy. MATERIALS AND METHODS: It is a retrospective, observational, analytic study carried out at a referral hospital in Western India. Collection of data was done for a period of 5 years, and various adverse outcomes were studied which included preterm delivery, low birth weight (LBW), stillbirths, congenital anomaly, and neonatal death. RESULTS: This study showed a preterm birth rate of 19% and LBW in 36% of cases. There was no significant association with congenital anomaly, stillbirth, or neonatal death. CONCLUSION: There was an association of exposure to efavirenz with an increased incidence of adverse pregnancy outcomes, especially LBW infants. This study emphasizes the requirement of large prospective studies to investigate fetomaternal outcomes in pregnant women exposed to efavirenz.

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