Drug utilization pattern in orthopaedic outpatient department of a tertiary care hospital in Kerala: a geriatric perspective

Background: Geriatric population due to the age related changes in pharmacokinetics and pharmacodynamics and the presence of comorbidities is vulnerable to drug interactions, adverse effects and high cost of therapy. This necessitates a periodic review of DU pattern in the geriatric population to ensure safe and effective treatment for them. The present study was undertaken to evaluate the DU pattern for medical conditions among the geriatric population in the Orthopaedic outpatient department (OPD) of a tertiary care hospital in Kerala.Methods: In this cross sectional observational study conducted in the Orthopaedics OPD of a tertiary care hospital, prescriptions were collected from patients attending the Orthopaedics OPD randomly over a period of 6 months. Out of these, prescriptions of male and female patients of age more than 60 years were sorted and analysed using World Health Organization drug prescribing indicators as well as additional parameters and the data was presented in the form of frequency and percentages using tables and charts.Results: A total of 800 prescriptions were collected and studied of which 76 (9.5%) belonged to patients from the geriatric population. Majority of the patients were in the age group of 61-70years (52.63%). Spondylosis (42.10%) was the most common indication for patients attending Orthopaedics OPD. Average number of drugs per prescription was 3.05 with a range between 1 and 5. Only 5.17% drugs were prescribed using generic name. Utilization from the essential drug list was 39.65%. The percentage of encounters in which an antibiotic and injection prescribed was 0% and 10.34% respectively. Of the total drugs prescribed 35% were FDCs. The most routinely prescribed drugs among the various classes were NSAIDs 34% followed by gastroprotectives (25%). The assessment of prescriptions with regard to completion and legibility was satisfactory.Conclusions: Current study pointed out deficiencies like polypharmacy, low prescribing of drugs by generic names, low prescribing of drugs from the essential drug list and higher use of FDCs. Use of antibiotics and injections was satisfactory and acceptable. Legibility and completion of prescription format was largely satisfactory. Proper strategies to rectify these deficiencies can ensure safe and effective treatment for geriatric patients

Predominantly myalgic phenotype caused by the c.3466G > A p.A1156T mutation in SCN4A gene

Objective: To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation. Methods: Twenty-nine Finnish patients identified with the c.3466G>A p.A1156T mutation in the SCN4A gene were extensively examined. In a subsequent study, 63 patients with similar myalgic phenotype and with negative results in myotonic dystrophy type 2 genetic screening (DM2-neg group) and 93 patients diagnosed with fibromyalgia were screened for the mutation. Functional consequences of the p.A1156T mutation were studied in HEK293 cells with whole-cell patch clamp. Results: The main clinical manifestation in p.A1156T patients was not myotonia or periodic paralysis but exercise-and cold-induced muscle cramps, muscle stiffness, and myalgia. EMG myotonic discharges were detected in most but not all. Electrophysiologic compound muscle action potentials exercise test showed variable results. The p.A1156T mutation was identified in one patient in the DM2-neg group but not in the fibromyalgia group, making a total of 30 patients so far identified. Functional studies of the p.A1156T mutation showed mild attenuation of channel fast inactivation. Conclusions: The unspecific symptoms of myalgia stiffness and exercise intolerance without clinical myotonia or periodic paralysis in p.A1156T patients make the diagnosis challenging. The symptoms of milder SCN4A mutations may be confused with other similar myalgic syndromes, including fibromyalgia and myotonic dystrophy type 2.Peer reviewe

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

Background:VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.Methods:The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.Results:Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.Conclusions:The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC

Cigarette Smoking and Human Gut Microbiota in Healthy Adults: A Systematic Review

The intestinal microbiota is a crucial regulator of human health and disease because of its interactions with the immune system. Tobacco smoke also influences the human ecosystem with implications for disease development. This systematic review aims to analyze the available evidence, until June 2021, on the relationship between traditional and/or electronic cigarette smoking and intestinal microbiota in healthy human adults. Of the 2645 articles published in PubMed, Scopus, and Web of Science, 13 were included in the review. Despite differences in design, quality, and participants’ characteristics, most of the studies reported a reduction in bacterial species diversity, and decreased variability indices in smokers’ fecal samples. At the phylum or genus level, the results are very mixed on bacterial abundance both in smokers and non-smokers with two exceptions. Prevotella spp. appears significantly increased in smokers and former smokers but not in electronic cigarette users, while Proteobacteria showed a progressive increase in Desulfovibrio with the number of pack-years of cigarette (p = 0.001) and an increase in Alphaproteobacteria (p = 0.04) in current versus never smokers. This attempt to systematically characterize the effects of tobacco smoking on the composition of gut microbiota gives new perspectives on future research in smoking cessation and on a new possible use of probiotics to contrast smoke-related dysbiosis

Circulating cell-free DNA and circulating tumor cells as prognostic and predictive biomarkers in advanced non-small cell lung cancer patients treated with first-line chemotherapy

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24\u20133.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies

Effects of vessel traffic on relative abundance and behaviour of cetaceans : the case of the bottlenose dolphins in the Archipelago de La Maddalena, north-western Mediterranean sea

Acknowledgements This study was part of the Tursiops Project of the Dolphin Research Centre of Caprera, La Maddalena. Financial and logistical support was provided by the Centro Turistico Studentesco (CTS) and by the National Park of the Archipelago de La Maddalena. We thank the Natural Reserve of Bocche di Bonifacio for the support provided during data collection. The authors thank the numerous volunteers of the Caprera Dolphin Research Centre and especially Marco Ferraro, Mirko Ugo, Angela Pira and Maurizio Piras whose assistance during field observation and skills as a boat driver were invaluable.Peer reviewedPostprin

The Wikiplantbase project: the role of amateur botanists in building up large online floristic databases

The Wikiplantbase project, started in 2013, provides a framework where the full set of georeferenced floristic records of Tuscany and Sardinia can be entered, stored, updated and freely accessed through the Internet. Mainly thanks to the collaboration of amateur botanists, data have accumulated quickly. All records entered by collaborators are submitted to the project coordinators, who are enabled to accept, modify, or reject them. As of 22 November 2016, Wikiplantbase #Toscana holds 116,402 verified floristic records (90% based on published literature, 5% on unpublished herbarium specimens, 5% on field observations), and Wikiplantbase #Sardegna 40,043 (77% published literature, 18% unpublished herbarium specimens, 5% on field observations ). The records include over 90% of the specific and subspecific taxa known for Tuscany and about 70% – but rapidly growing – of those known for Sardinia. The most recorded species are Quercus ilex L. (Fagaceae) for Tuscany and Pistacia lentiscus L. (Anacardiaceae) for Sardinia. With minor software tweaking, the online platform Wikiplantbase might be adopted in other contexts, resulting in a well connected network of regional floristic databases suited to exploit the involvement – still largely untapped – of nonacademic collaborators, as advocated by citizen science

Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

Background. Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. Methods. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2A genes. Results. For melanoma susceptibility, investigations at germline level indicated that p16CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2A silencing). Conclusion. Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis