Oncologist’s knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study

[Purpose]: Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for oncologic patients, which remain under diagnosed and undertreated. In 2012, the Spanish Society of Medical Oncology (SEOM) published a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP.[Methods]: Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline.[Results]: A total of 83 oncologists with a mean experience of 13 years responded. Overall, 82% were aware of different guidelines to manage BTcP. Notably, attitudes toward guidelines were highly positive and there was nearly unanimous agreement that CPG provided the best scientific evidence available (99%), on the minimum information to be gathered for the medical history (100%), on the need for a specific treatment for BTcP (100%), and fentanyl as the first-choice drug (99%). Interestingly, there were discrepancies between what oncologists agreed with and what they do in clinical practice. In fact, 87.6% declare full compliance with SEOM guideline, although adherence to registration of BTcP data in medical records ranged from 30.1 to 91.6% (mean 64.5%); therapeutic management compliance was higher ranging from 75.9 to 91.6%. Main barriers identified were time pressure together with vague statements and limited dissemination of the guidelines.[Conclusion]: Despite oncologist’s clinical practice is increasingly guided by GPC, it suffers from limited compliance, at least in part due to suboptimal statements. Improved dissemination and education are needed to enhance guideline implementation.This study was funded by Kyowa Kirin Farmacéutica S. L.U. through Fundación ECO

Frequency and clinical patterns of stroke in Iran - Systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Cerebrovascular disease is the second commonest cause of death, and over a third of stroke deaths occur in developing countries. To fulfil the current gap on data, this systematic review is focused on the frequency of stroke, risk factors, stroke types and mortality in Iran.</p> <p>Methods</p> <p>Thirteen relevant articles were identified by keyword searching of PubMed, Iranmedex, Iranian University index Libraries and the official national data on burden of diseases.</p> <p>Results</p> <p>The publication dates ranged from 1990 to 2008. The annual stroke incidence of various ages ranged from 23 to 103 per 100,000 population. This is comparable to the figures from Arab Countries, higher than sub-Saharan Africa, but lower than developed countries, India, the Caribbean, Latin America, and China. Similarly to other countries, ischaemic stroke was the commonest subtype. Likewise, the most common related risk factor is hypertension in adults, but cardiac causes in young stroke. The 28-day case fatality rate is reported at 19-31%.</p> <p>Conclusions</p> <p>Data on the epidemiology of stroke, its pattern and risk factors from Iran is scarce, but the available data highlights relatively low incidence of stroke. This may reflect a similarity towards the neighbouring nations, and a contrast with the West.</p

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Linezolid resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Iran

The management of multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) presents a main challenge and the drug options for treating these infections are very limited. Linezolid (LNZ) has recently been approved for the treatment of MDR and XDR-TB. But, there are narrow data on genotypic and phenotypic LNZ resistance in clinical isolates. So, we aimed to determine the prevalence of LNZ resistance and to identify the mutations associated with LNZ resistance among clinical MDR-TB isolates. The minimum inhibitory concentration (MIC) values of LNZ, for 22 MDR-TB isolates were determined by broth microdilution method. All MDR-TB isolates were sequenced in the rrl and rp1C genes conferring LNZ, resistance. LNZ, resistance was found in 3 (13.6%) of 22 MDR-TB isolates. The MICs of LNZ were 8 mu g/mL for two isolates and 16 mu g/mL for one isolate. The 421 (A/G) and 449 (T/A) mutations in rplC gene were detected in one of the LNZ-resistant isolates. There was no mutation in rrl gene. The results reveal that the prevalence of LNZ-resistant isolates is 13.6% among MDR-TB isolates and drug susceptibility testing (DST) against LNZ is useful in the management of complicated and drug-resistant cases. However, further studies could identify other possible genetic mechanism of resistance in TB

Toxin-antitoxin Genes Expression in Multidrug-resistant Mycobacterium tuberculosis Isolates under Drug Exposure

INTRODUCTION: Toxin-antitoxin systems (TAs) are highly conserved in Mycobacterium tuberculosis (Mtb). The TAs role in maintaining and disseminating drug resistance in bacterial populations has been indicated. So, we aimed to analyze the expression level of mazEF-related genes in drugsusceptible and multidrug-resistant (MDR) Mtb isolates under isoniazid (INH) and rifampin (RIF) stress. METHODS: We obtained 23 Mtb isolates, including 18 MDR and 5 susceptible isolates, from the Ahvaz Regional TB Laboratory collection. The expression levels of mazF3, mazF6, and mazF9 toxin genes, and mazE3, mazE6, and mazE9 antitoxin genes in MDR and susceptible isolates were evaluated by quantitative real-time PCR (qRT-PCR) after exposure to RIF and INH. RESULTS: The mazF3, F6, and F9 toxin genes were overexpressed in at least two MDR isolates in the presence of RIF and INH, in contrast to mazE antitoxin genes. More MDR isolates were induced to overexpress mazF genes by RIF than INH (72.2 vs. 50). Compared to the H37Rv strain and susceptible isolates, the expression levels of mazF3,6 by RIF and mazF3,6,9 by INH were significantly upregulated in MDR isolates (p<0.05), but no remarkable difference was detected in the expression level of mazF9 genes by INH between these groups. In susceptible isolates, the expression levels of mazE3,6 by RIF and mazE3,6,9 by INH were induced and enhanced significantly compared to MDR isolates, but there was no difference between MDR and H37Rv strain. CONCLUSION: Based on the results, we propose that mazF expression under RIF/INH stress may be associated with drug resistance in Mtb in addition to mutations, and the mazE antitoxins may be related to enhanced susceptibility of Mtb to INH and RIF. Further experiments are needed to investigate the exact mechanism underlying the TA system's role in drug resistance