Drug utilization study in otorhinolaryngology outpatient department in a tertiary care teaching hospital

Background: Drug utilization research is defined by the World Health Organization (WHO) as marketing, distribution, prescription, and use of drugs in society, with special emphasis on the resulting medical, social, and economic consequences. Drug utilization study identifies the problems that arise from prescription and highlights the current approaches to the rational use of drugs. The main aim of the study is to assess the pattern of drug usage and the rationality of drug use in Otorhinolaryngology out-patient department (OPD).Methods: A prospective observational study was conducted in the OPD of Otorhinolaryngology at tertiary care hospital, Mandya, Karnataka, over a period of one year. Prescriptions of all OPD patients were collected, relevant information entered in a specially designed proforma and analysed using descriptive statistics.Results: A total of 21058 drugs were prescribed out of 8028 prescriptions. Majority of the patients were male (51%). Antimicrobials were the most commonly prescribed drugs (28%), followed by antihistamines (25%), antipyretics (20.5%).Most of the drugs 18576 (88.2%) were prescribed by oral route, followed by topical route. Majority of the drugs were prescribed by the generic names (86.5%). Most common type of infection was ear infection (3176), followed by throat infection (2848) and nose infection (2004).Conclusions: The present study showed that among antimicrobial agents, β lactams were commonly prescribed drugs in the department of Otorhinolaryngology. The maximum number of cases was diagnosed with ear infections and majority of the drugs were prescribed orally

A prospective observational study of drug usage in the management of snake bite patients and their outcome in a tertiary care teaching hospital

Background: The objectives of the study were to assess the pattern of management of snakebite especially with respect to use of anti- snake venom and other supportive treatment given and to assess the effect of anti-snake venom on different types of snakebite and to assess their outcome.Methods: A prospective observational study was conducted over a period of 6 months, after getting approval from Institutional Ethics committee. Total of 144 snake bite patients were analysed for six months duration for use of anti-snake venom and other supportive treatment in their management and were assessed for their outcome like recovery, morbidity and mortality.Results: Out of 144 snake bite patients analysed, 71.5% had poisonous type and 28.4% had non- poisonous type of snake bite. Among the total number of snakebites, 47.2% were unknown type and among the known type 25% were viper, 13.2% cobra, 7.6% krait, 6.3% sea snake and 0.7% green snake. Anti-snake venom (ASV) was given to 62 patients depending on severity, of which, 22 patients developed reaction to ASV. Patient with reaction to ASV were treated with corticosteroid and antihistamine injection. Morbidity was seen in 29.1% of patients who developed either cellulitis or gangrene of bitten area, which was more commonly seen among viper bite patients (54.7%).Conclusions: Snakebite is one of the commonest tropical diseases leading to envenomation and poisoning especially in rural areas of tropical countries which has to be treated as early as possible to prevent complications. Majority of the cases in our study were of viper bite and most of them have recovered after treatment

A prospective study of drug utilization pattern in cardiac intensive care unit at a tertiary care teaching hospital

Background: Cardiovascular diseases remain the most common cause of sudden death. Appropriate drug therapy in cardiac intensive care unit (CICU) is crucial in managing cardiovascular emergencies and to decrease morbidity and mortality. The present study was conducted to observe the emergency cardiac diseases which are most frequently being treated and to study the prescribing prevalence among inpatients in CICU.Methods: A prospective, observational study was carried out among 102 patients admitted in CICU at a tertiary care teaching hospital, Karnataka, for a period of 3 months. Demographic data, clinical history, and complete drug therapy received during their stay in CICU was noted.Results: In our study, males (64.7%) had a higher incidence of cardiovascular emergencies than females (35.3%). Hypertension (32.4%) and Type 2 diabetes mellitus (28.4%) were the frequently associated co-morbid conditions. Antiplatelet drugs 80 (78.4%) was most commonly prescribed, followed by hypolipidemic drugs 75 (73.5%) and anticoagulants 65 (63.7%). The mean duration of stay in the hospital was 4.79±1.9 days. The average number of drugs per prescription was 7.8±2.2. Percentage of drugs prescribed by generic names was 52.9%. The percentage of drugs prescribed from essential drug list was 75.1%.Conclusions: Antiplatelet drugs were the most frequently prescribed drug group. Mean number of drugs per prescription were high. The prescribing pattern could be improved by reducing the number of drugs per prescription and by prescribing generic drugs to reduce the economic burden of the patients

Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia

: Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248). Results of both cohorts were combined in a meta-analysis. In primary analysis, patients with SIOP Boston Ototoxicity Scale grade ≥1 were considered cases, and patients with grade 0 were controls. Variants with a p-value <10-5 were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in TSPAN5, RBBP4P5, AC010090.1 and RNU6-38P were suggestively associated with platinum-induced ototoxicity. The lowest p-value was found for rs7671702 in TSPAN5 (odds ratio 2.0 (95% confidence interval 1.5-2.7), p-value 5.0 × 10-7). None of the associations were significant in the replication cohort, although the effect directions were consistent among all cohorts. Validation and functional understanding of these genetic variants could lead to more insights in the development of platinum-induced ototoxicity

ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while those harboring TP53-mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992

Recurrent SPECC1L-NTRK fusions in pediatric sarcoma and brain tumors

The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. These fusions arose either through a simple balanced rearrangement or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L-NTRK2 expression are sensitive to a TRK inhibitor drug. We report here that SPECC1L-NTRK fusions can arise in a range of pediatric cancers. Although WGS and RNA-seq are not required to detect NTRK fusions, these techniques may be of benefit when NTRK fusions are not suspected on clinical grounds or not identified by other methods