A randomized prospective study to compare the efficacy and safety of budesonide plus formoterol and tiotropium plus formoterol in patients having mild to moderate chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is a leading respiratory illness affecting the quality of lives around the world. The present study aims to compare the efficacy and safety of combination of inhaled corticosteroid (ICS) and long acting β2 agonist (LABA) with long acting β2 agonist and long acting muscarinic antagonist (LAMA) in treatment of mild to moderate COPD in a tertiary care hospital.Methods: Total 132 patients with COPD were recruited on the basis of inclusion and exclusion criteria for 8 weeks study from outpatient clinic. A complete pulmonary examination including spirometry examination was done to rule out severe and very severe forms of COPD. Spirometry was performed at the time of recruitment for evaluation of forced expiratory volume in one second (FEV1) and measurement of SpO2 at the time of recruitment at 2 weeks and 8 weeks. Appropriate statistical methods were used to compare the qualitative and quantitative primary and secondary efficacy end points, p value <0.05 was considered significant.Results: On analysis, there was a significant difference (p<0.05) was observed in FEV1 and SpO2 from baseline in ICS plus LABA group (n=66). A similarly significant difference (p<0.05) was observed in LABA and LAMA group (n=66). On comparison between ICS plus LABA and LABA plus LAMA no significant difference in FEV1 and SpO2 was observed between the two groups.  More adverse drug reactions were observed in ICS plus LABA group than LAMA plus LABA group.Conclusions: Combination of ICS and LABA combination is as effective as combination of LABA and LAMA in patients having mild to moderate COPD. However, LABA and LAMA combination is preferable because it is associated with fewer side effects

Narrative Review of Nimesulide in Adults: Current Scenario

Nimesulide, a nonsteroidal anti-inflammatory drug (NSAID), has been used as an effective treatment regimen for patients aged &gt;12 years for fever, acute pain, acute tendinitis, osteoarthritis and dysmenorrhea. It is reported to be a superior antipyretic and anti-inflammatory drug than paracetamol and aspirin, respectively, and is equal to any of the NSAIDs alone in terms of analgesia. This paper reviews the current scenario of nimesulide in adult patients, concerning clinical evidence, use in special population and expert opinion. Overall, in comparison to other NSAIDs, including coxibs, nimesulide has a promising overall efficacy, safety and tolerability profile, as well as a satisfactory benefit/risk evaluation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Formulation and evaluation of microemulsion containing ketoprofen

Ketoprofen microemulsion is presently considered as the novel drug delivery system. It shows prolonged action. Ketoprofen is a BCS II class drug. It is a highly lipophilic poorly soluble drug with low oral bioavailability. The present aim was to increase the solubility by a microemulsion system for topical delivery. Microemulsions are clear, stable and isotropic liquid. They show advantages such as spontaneous preparation, scale up, ease of preparation, improving drug solubility of hydrophobic drugs. It is also used to increase the bioavailability of drug. These also aim at controlling the bioavailability of various drug molecules. The review put forward the development in a microemulsion-containing system. They improve solubility, chemical stability and oral bioavailability of poorly water-soluble drugs. There is a formulation of four different batches. The batches differ in the quantity of surfactant and co-surfactants

Analytical method development and validation of rivaroxaban in bulk and pharmaceutical dosage form by using RP-HPLC

A simple, specific, accurate, and precise reverse phase high performance liquid chromatography (RP-HPLC0 method was developed and validated to analyse Rivaroxaban bulk dosage form. Using&nbsp; Sun Q C18 &nbsp;HPLC column separation was carried out. This was maintained at ambient temperature. During separation mobile phase consist of Acetonitrile : Buffer(sodium acetate buffer) 80:20 was delivered at a flow rate of 1mL/min. Using UV detector analysis was carried out at the wavelength 249 nm. RP-HPLC method was validated by using various parameter like system suitability, linearity, specificity, precision, limit of detection, limit of quantification and robustness. The RP-HPLC method was found to be linear over the concentration range from 5-30 µg/mL (r2 =0.994). Retention time for bulk rivaroxaban was found to be 3.69 min. LOQ of method was 1.331 µg/mL and LOD 0.439 µg/mL. Thus the developed RP-HPLC method was found to be robust which can be applied for the regular analysis of Rivaroxaban in the bulk as well as pharmaceutical dosage for

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts