Off-label use of antibiotics in hospitalised children in a tertiary care teaching hospital

Background: Children constitute one-third of the population and they suffer from a variety of infectious diseases and are commonly prescribed antibiotics. Most of the antibiotics lack sufficient information on safety and efficacy in children and are thus prescribed off-label. This study was envisaged to assess the off-label use of antibiotics in hospitalized children.Methods: Total 120 patients were included in the study. Off-label use was determined on the basis of product literature and National Formulary of India. Descriptive statistics was used to present the data i.e. percentage; proportions, frequency, mean and standard deviation using Microsoft excel worksheet.Results: A total of 791 drugs from different classes were prescribed to 120 patients with a mean of 6.6±2.68 drugs described per patient during their stay in the hospital. 100 out of 120 (83%) patients were prescribed at least one antibiotic during their stay in the hospital. Out of the 204 antibiotics prescribed, 43(21%) were prescribed off-label. Antibiotic dose was the most common reason followed by age (1month-1 year more than 2-6 years of age) and frequency in off-label use.Conclusions: Antibiotics are commonly prescribed to children with substantial off-label use. The same must be seriously addressed by the policy makers and stakeholders in order to promote their rational use

Quality of prescriptions in hospitalized children suffering from acute and persistent diarrhoea

Background: Diarrhoea is a major public health problem in children worldwide. It continues to be a major health challenge, especially in developing countries, despite the availability of regularly updated standard treatment guidelines. Non-compliance to such guidelines by the physicians has been a long standing story. The treatment is often marred with incapacitating prescription of drugs besides neglecting even the basic tenets of good prescribing. As a result, the quality of such prescriptions for diarrhoeal disorders in children remains poor. To gauge the magnitude of this problem in this setup towards possible corrective measures, the study was aimed to audit prescription practices in the management of acute and persistent diarrhoea in hospitalised children up to five years of age.Methods: An observational study was conducted in 100 patients of either gender in the age group up to 5 years admitted with acute and persistent diarrhoea. A detailed medical history from the parents/guardians and the details of prescription from the time of admission till the discharge of the patient were obtained. Quality of prescriptions was analysed using prescription quality index (PQI) tool, a validated comprehensive tool described by Hassan et al in 2010. Based on this tool, prescription with the total PQI score of ≤ 31 were interpreted as poor quality, scores with 32 to 33 as medium quality and scores 34 to 43 as high quality with a possible maximum score of ‘43’.Results: Based on the PQI tool for 100 children, 60 prescriptions were found to be of poor quality. Only 2 prescriptions were of medium quality, whereas 38 prescriptions were in high quality range. Average mean±SD score of prescriptions with poor quality was 25.2±1.48, ranging from 21 to 31. The mean±SD of prescriptions with medium quality was observed to be 32±0 and for prescriptions of high quality was 38.07±2.28. The total average mean score of all prescriptions was 30.23±6.50. Poor quality prescriptions were particularly observed for the patients with the diarrhoea with No dehydration.Conclusions: Prescription appropriateness in spite of available guidelines continues to be a big challenge in the adequate management of patients with diarrhoeal disorders under the age group of five years in a tertiary care centre in India

Knowledge attitude and practice of pharmacovigilance among nursing professionals in a tertiary care teaching hospital in Dehradun, Uttarakhand

Background: Pharmacovigilance deals with identification, assessment and prevention and reporting of adverse drug reaction (ADR), play a pivotal role in ensuring safe use of drugs. However, in spite of having well established ADR reporting system in India and worldwide, the ADR underreporting is a big challenge till date. It is therefore very important to assess the level of awareness of Pharmacovigilance among healthcare professionals to identify the factors affecting ADRs reporting. The objective of the study was to evaluate knowledge, attitude and practice of pharmacovigilance among nursing professionals in a tertiary care teaching hospital in Dehradun, India.Methods: It was a cross sectional observational study conducted at HIMS over a period of 1 year. Nursing professionals who work in internal medicine, Surgery, PAC and intensive care unit (ICU) were included in this study. A self-administered questionnaire comprising of 15 items related to ADRs and Pharmacovigilance programme of India (PvPI) activity was provided to them and sufficient time to fill the questionnaire was given. The completely filled questionnaire was collected and data was analyzed using SPSS ver.20.0.Results: A total of 415 participants were included in the study. The mean age of the participant was 28.52 years. The number of female was more than male participants. Majority of participant (56%) couldn’t answer the meaning of pharmacovigilance. Only 25% participants were aware about ADR reporting process to ADR monitoring centre (AMC). Although majority of the participants understand the necessity of ADR reporting and aware about AMC centre and PvPI, but most of them showed unfamiliarity about ADR reporting form and previous experience of any kind of ADR. The most common reason for not reporting the ADR was difficulty in deciding the nature of adverse effects (AE) (44%) followed by lack of time (30%). Majority of participant (67%) denied any previous pharmacovigilance training and almost all (98%) have shown their interest in PvPI training.Conclusions: Nursing professionals in our hospital may lack adequate knowledge about ADR reporting and may need more education and training on the National Pharmacovigilance System and ADR reporting process

COMPARATIVE STUDY OF HORMONAL AND NON HORMONAL TREATMENTS FOR THE MANAGEMENT OF MENOPAUSAL SYMPTOMS

Objective : This study was conducted with the objective of comparing safety and efficacy of hormonal treatment and non hormonal alternatives for the management of menopausal symptoms.Materials and Methods: A total of 40 patients suffering from menopausal symptoms were recruited to the study protocol and were divided into 4 groups according to the treatment they received, with 10 patients in each group. Group A received conjugated estrogen and medroxy progesterone acetate, Group B received Tibolone, Group C received Isoflavone and Group D received Vitamin E. Efficacy of the treatment was evaluated by improvement in symptomatic score and safety of the treatment was assessed on the basis of adverse effects reported and relevant laboratory investigations.Results: Most of the symptoms were significantly improved in groups A and B (p< 0.01) while in groups C and D significant improvement was observed in hot flushes, sweating and insomnia (p<0.05). On comparative analysis there was no significant difference in the efficacy between groups A and B and between groups C and D. On the other hand significant difference was observed in the efficacy when groups A and B were compared with groups C and D (p<0.01). Only mild tolerable side effects were reported by the patients in all the groups with slightly higher incidence in groups A and B.Conclusions : Hormonal treatment is very efficacious for the early relief of menopausal symptoms. Isoflavone and vitamin E can be considered as a satisfactory treatment alternative when for any reasons hormonal treatment cannot be used.KEY WORDS:  HRT, Tibolone , Isoflavone, Menopausal symptom

Comparative evaluation of levetiracetam and valproic acid as monotherapy on cognitive impairment in patients of epilepsy

Background: Cognitive decline with AEDs (Anti-epileptic drugs) is associated with learning and memory deficits especially in the younger age group. The data regarding the impact of levetiracetam and valproic acid as monotherapy on cognition in epileptic patients is scarce. The present study was done for evaluation of cognitive decline associated with the use of AEDs.Methods: Present study was a prospective study on 60 patients on AEDs for a period of 12 weeks. Patients were enrolled from the Department of Neurology, Swami Rama Himalayan University, Dehradun, Uttarakhand, India and divided into group A (levetiracetam) and group B (valproic acid) with 30 patients in each group. Permission from the institutional ethics committee and written informed consent was taken from all the patients. They were analyzed for cognitive impairment using MMSE and MoCA scales at baseline and 12 weeks.Results: The mean duration of disease was 2.13±1.1 years and 2.08±1.1 years and mean age of the patients was 14.67±1.9 years in group A and 16.20±1.6 years in group B. GTCS was present in 31 patients (52%) followed by partial seizures in 29 patients (48%). The mean change in the MMSE scores from baseline to 12 weeks was significant in group A 1.30±1.1 (p value <0.05) and change group B was -0.20±1.4 not statistically significant. The mean change was observed in MoCA scores from baseline to 12 weeks was significant in both groups A and B by 1.17±1.1 and -0.70±1.1 respectively (P value <0.05).Conclusions: Patients on levetiracetam showed cognitive improvement, whereas patients on valproic acid showed a decline in the MMSE and MoCA scores

Novel nanoparticle formulation of Sabizabulin (VERU-111) for pancreatic cancer treatment

Background: Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortality in the United States due to very limited therapeutic options. Thus, developing novel therapeutic strategies will help for the management of this disease. We recently identified VERU-111, a novel synthetic molecule which showed potent anti-cancer effect against PanCa via targeting clinically important βIII and βIV tubulin isoforms. In this study, we synthesized and characterized its novel nanoformulation (MNP-VERU) and evaluated its therapeutic effects in vitro and xenograft mouse model. Methods: MNPs were prepared by chemical precipitation method and loaded with VERU-111 using diffusion method. This formulation was characterized for particle size, chemical composition, and drug loading efficiency, using various physico-chemical methods (TEM, FT-IR, DSC, TGA, and HPLC). The internalization of MNP-VERU was achieved after 6 hours incubation with MNP-VERU in PanCa cells. To determine therapeutic efficacy of MNP-VERU, we performed various in vitro (MTS, wound healing, boyden chamber real-time xCELLigence, and apoptosis assays) and in vivo (mouse tumor xenograft) studies using PanCa. Effect of MNP-VERU on various key oncogenic signaling pathways, and miRNAs was evaluated by Western blot, immunohistochemistry (IHC), confocal microscopy, qRT-PCR and in situ hybridization (ISH) analyses respectively. Results: Our novel MNP-VERU formulation provided average size of 110 nm in dynamic light scattering (DLS) and exhibited -8.23 to -11.65 mV zeta potential with an outstanding loading efficiency (94%). Cellular uptake and internalization studies demonstrate that MNP-VERU escape lysosomal degradation, providing efficient endosomal release to cytosol. MNP-VERU showed remarkable anti-cancer potential in various PanCa cells (Panc-1, AsPC-1, HPAF-II, BxPC-3, MiaPaca) and more effectively repressed βIII and βIV tubulin isoforms via restoring the expression of miR-200c. MNP-VERU more effectively suppressed AsPC-1 cells derived xenograft tumors in athymic nude mice. Conclusions: Taken together, our results suggest that MNP-VERU has more anti-cancer potential than free VERU-111 against PanCa. MNP-VERU may reduce the toxicity and improve the bioavailability of free VERU-111 and could be used for the management of PanCa and

Internet of Things in Water Management and Treatment

The goal of the water security IoT chapter is to present a comprehensive and integrated IoT based approach to environmental quality and monitoring by generating new knowledge and innovative approaches that focus on sustainable resource management. Mainly, this chapter focuses on IoT applications in wastewater and stormwater, and the human and environmental consequences of water contaminants and their treatment. The IoT applications using sensors for sewer and stormwater monitoring across networked landscapes, water quality assessment, treatment, and sustainable management are introduced. The studies of rate limitations in biophysical and geochemical processes that support the ecosystem services related to water quality are presented. The applications of IoT solutions based on these discoveries are also discussed

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19:a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

This study was funded by an investigator-initiated research grant from Insmed (Bridgewater, NJ, USA). The authors acknowledge the funding and logistical support from the UK National Institute for Health and Care Research.Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings: Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57-0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation: Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19.Publisher PDFPeer reviewe