Antibiotic therapy in sepsis: No next time for a second chance!

WHAT IS KNOWN AND OBJECTIVE: Sepsis is a life-threatening organ dysfunction associated with a high rate of morbidity and mortality. Appropriate antibiotic therapy remains the cornerstone of sepsis and septic shock management. COMMENT: Although the early initiation of antimicrobial agents in the treatment of sepsis is widely acknowledged, the selection and adjustment to optimal dosage can be equally important. Since significant pathophysiological changes in the critically ill patients lead to altered pharmacokinetics of antibiotics, early consideration of pharmacokinetic/pharmacodynamic (PK/PD) properties is necessary for optimal antibiotic dosing in sepsis and should be integrated in practice. WHAT IS NEW AND CONCLUSION: Where possible, an individualized antibiotic dosing approach through the application of therapeutic drug monitoring (TDM) service should replace the conventional dosing in critically ill patients with sepsis. Finally, antimicrobial stewardship can help improve clinical outcomes.

Do serum GDNF levels correlate with severity of Alzheimer's disease?

INTRODUCTION: A growing body of evidence that glial cell line-derived neurotrophic factor (GDNF) levels are probably involved in pathogenesis and disease course of Alzheimer's disease (AD) suggested that its blood levels could potentially be used as a biomarker of AD. The aim of this study was to compare serum GDNF levels in patients with AD and age-matched controls. METHODS: Serum concentrations of GDNF were compared in 25 AD patients and 25 healthy volunteers using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Severity of the disease in AD patients was assessed using Functional Assessment Staging (FAST). Cognitive assessment of the patients was done using the Mini-Mental State Examination (MMSE). RESULTS: Mean GDNF levels were found to be 2.45 ± 0.93 ng/ml in AD patients and 4.61 ± 3.39 ng/ml in age-matched controls. There was a statistically significant difference in GDNF serum levels in patients with AD compared to age-matched controls (p = 0.001). Moreover, GDNF serum levels were significantly correlated with disease severity (p < 0.001) and cognitive impairment (p < 0.001). CONCLUSION: This study showed that serum levels of GDNF are significantly decreased in AD patients in comparison with age-matched controls, thus suggesting a potential role of GDNF as a disease biomarker. However, a comprehensive study of changes in serum levels of multiple neurotrophic factors reflective of different neurobiological pathways in large-scale population studies is recommended.

Association of the mir-499 polymorphisms with oral cavity and oropharyngeal squamous cell carcinoma in an Iranian population.

BACKGROUND: Oral squamous cell carcinoma (SCC) is the most common oral malignancy. Some evidence indicated that there is a correlation between microRNA single nucleotide polymorphisms and the risk of oral cancer. The aim of the current study was to investigate the association between mir-499 polymorphism with the risk of oral cavity and oropharyngeal SCC in a subset of Iranian Population. MATERIALS AND METHODS: In this case-control pilot study total of 112 participants including 56 histopathlogically confirmed oral and oropharyngeal SCC patients and 56 age- and sex-matched controls were included The mir-499 rs3746444 T/C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism method. The comparisons of the distribution of the allele and genotype frequencies were performed using Chi-square test, and P < 0.05 was considered as statistically significant. RESULTS: The result of the present study indicated that the frequency distribution of mir-499 was not significantly different between cases and controls (P > 0.05). We also did not find any significant association between the risk of the cancer and mir-499 polymorphisms in the recessive (Odds ratio [OR]: 6.60; 95% confidence interval [CI]: 0.77-56.74; P = 0.11) and dominant (OR: 1; 95% CI: 0.37-2.74; P = 1) inheritance models even after adjustment for smoking. CONCLUSION: The results of the present study indicated that the polymorphisms of mir-499 are not associated with the risk of oral and oropharyngeal SCC in Iranian population. However, further large scale studies are needed to validate our findings.

In vivo analgesic and anti-inflammatory effects of the essential oil from Tanacetum balsamita L

Tanacetum balsamita locally called Shahesparam is an aromatic plant that grows widely in Azerbaijan Province, Iran. Due to the widespread use of T. balsamita as a pain killer and relief of inflammatory based disorders in Iranian folk medicine and considering the high content of essential oil in T. balsamita aerial parts, we were prompted to investigate the anti-nociceptive and anti-inflammatory properties of T. balsamita essential oil (TBEO) for the first time. The carrageenan-induced Paw Edema was used for inflammation evaluation in rat, and hot-plate method was used for pain assessment in mice. Different doses of TBEO were administered. Morphine and Mefenamic acid were used as the standard drugs in anti-nociceptive and anti-inflammatory evaluation tests, respectively. TBEO (100 mg/kg) showed significantly anti-nociceptive activity in hot-plate test. The anti-inflammatory activity of TBEO was found to be more than mefenamic acid. The studied oil was analyzed by GC and GC-MS. The major component of the oil was characterized as carvone (39.8%) which might be responsible for the observed activities. The results suggested that TBEO possessed biologically active constituents that had significant analgesic and anti-inflammatory effects which support the ethno-medicinal claims of the plant application in the management of pain and inflammation.

Attitudes of medical students towards incentives offered by pharmaceutical companies -- perspective from a developing nation -- a cross-sectional study.

BACKGROUND: A training physician has his first interaction with a pharmaceutical representative during medical school. Medical students are often provided with small gifts such as pens, calendars and books, as well as free lunches as part of drug promotion offers. Ethical impact of these transactions as perceived by young medical students has not been investigated in Pakistan before. This study aimed to assess the association of socio-demographic variables with the attitudes of medical students towards pharmaceutical companies and their incentives. METHODS: As part of a cross-sectional survey, a validated questionnaire previously used for assessing attitude of medical students towards pharmaceutical industry, was modified, pre-tested and distributed among consenting clinical year students at DUHS and AKU. Questions included acceptability of pharmaceutically sponsored gifts, events and tuition fee, and their impact on future prescription. Responses were graded as agree, disagree or neutral which were then scored according to the AMSA guidelines of ethical conduct. RESULTS: Out of a total of 353 targeted students 303 responded, corresponding to a response rate of 85.8%. Responses indicated that 42.7% students believed in no interaction with drug companies during medical school. However, 81% of students favored pharmaceutical sponsorship of student-body events/seminars at medical colleges. More than one-third of the students were comfortable receiving gifts from drug companies. Overall, the results of this study offer an interesting comparison between the students of a private medical school (AKU) and a public medical school (DUHS); AKU students exhibited a greater degree of mistrust towards drug information provided by pharmaceutical companies compared to DUHS students (p = 0.040). Furthermore, when asked if there was a need to incorporate guidelines in the undergraduate curriculum with regard to interaction with drug companies, 84.2% students at AKU agreed, compared to 54.9% at DUHS. Medical student Attitude Scores are more or less similar to each other independent of their various demographical differences. CONCLUSION: This study highlights that medical students in our population have a high level of acceptability towards incentives offered by pharmaceutical industry and that formal guidance regarding the subject should be incorporated into medical curriculum.