Neuroprotective role of a monoterpene (thymol) on diazepam induced withdrawal symptoms in rats.

Benzodiazepine administration is known to be related to tolerance and a withdrawal syndrome on sudden cessation. Thymol possesses multiple biological properties especially in the pathogenesis of different brain disorders. However, to the best of our knowledge there is no study that relates the use of thymol to benzodiazepine induced withdrawal symptoms. Therefore the aim of the current study was to investigate the usefulness of thymol in the treatment of benzodiazepine withdrawal syndrome in rats. Animals were divided into four groups, thymol (40mg/kg/ml), diazepam (4 mg/kg), thymol + diazepam and vehicle control group. The treatment was given for 14 days and then suddenly ceased. After 24 h animals were tested in different behavioral paradigms such as physical signs for withdrawal, marble burying test, inverted screen test, elevated plus maze, passive avoidance test and open field activity. The results of the present study revealed that co-administration of thymol significantly reduced the withdrawal symptoms induced by diazepam. Our results further suggest that administration of thymol not only ameliorates rebound anxiety associated with diazepam withdrawal but also improves motor and memory impairment in rats.

The Neuro-Vascular Consequence of Diabetes: Foot Amputation and Evaluation of its Risk Factors and Health-Related Economic Impact.

BACKGROUND: The rising prevalence of type 2 diabetes mellitus (T2DM) with the huge burden of diabetic foot amputation is a challenge to the health economy of Pakistan and other countries. Identification of various risk factors for amputation, along with its financial burden, is needed to address this problem. OBJECTIVES: This study aimed to determine the financial burden and risk factors associated with T2DMrelated foot amputation. METHODS: Retrospective hospital-based study from January 2017 to December 2018. Patients with T2DM with and without amputation were enrolled. The direct medical costs of amputation along with various risk factors, were determined. Risk factors were evaluated by logistic regression analysis. RESULTS: A total of 1460 patients with T2DM were included; 484 (33%) patients had an amputation. The mean total cost of below knee, fingers and toe amputation was 886.63±23.91, 263.35 ±19.58 and 166.68 ± 8.47 US$, respectively. This difference among groups was significant (p<0.0001). Male gender (odds ratio, OR: 1.29, 1.01-1.63, p=0.037), peripheral artery disease (OR: 1.93, 1.52-2.46, p=0.000), peripheral neuropathy (OR: 1.31, 1.40-1.63, p=0.000), prior diabetic foot ulcer (OR: 2.02, 1.56- 2.56, p=0.000) and raised glycated haemoglobin (HbA1c) (OR: 3.50, 2.75-4.4, p=0.000) were risk factors for amputation. CONCLUSION: The health-related financial impact of amputations is high. Peripheral artery disease, peripheral neuropathy, prior diabetic foot ulcer and raised HbA1c were risk factors for amputation.

Outcomes of Protocol-Driven Care of Critically Ill Severely Anemic Patients for Whom Blood Transfusion Is Not an Option.

OBJECTIVE: To compare the outcomes of severely anemic critically ill patients for whom transfusion is not an option ("bloodless" patients) with transfused patients. DESIGN: Cohort study with propensity score matching. SETTING: ICU of a referral center. PATIENTS: One hundred seventy-eight bloodless and 441 transfused consecutive severely anemic, critically ill patients, admitted between May 1996 and April 2011, and having at least one hemoglobin level less than or equal to 8 g/dL within 24 hours of ICU admission. Patients with diagnosis of brain injury, acute myocardial infarction, or status postcardiac surgery were excluded. INTERVENTIONS: Allogeneic RBC transfusion during ICU stay. MEASUREMENTS AND MAIN RESULTS: Primary outcome was in-hospital mortality. Other outcomes were ICU mortality, readmission to ICU, new electrocardiographic or cardiac enzyme changes suggestive of cardiac ischemia or injury, and new positive blood culture result. Transfused patients were older, had higher hemoglobin level at admission, and had higher Acute Physiology and Chronic Health Evaluation II score. Hospital mortality rates were 24.7% in bloodless and 24.5% in transfused patients (odds ratio, 1.01; 95% CI, 0.68-1.52; p = 0.95). Adjusted odds ratio of hospital mortality was 1.52 (95% CI, 0.95-2.43; p = 0.08). No significant difference in ICU readmission or positive blood culture results was observed. Analysis of propensity score-matched cohorts provided similar results. CONCLUSIONS: Overall risk of mortality in severely anemic critically ill bloodless patients appeared to be comparable with transfused patients, albeit the latter group had older age and higher Acute Physiology and Chronic Health Evaluation II score. Use of a protocol to manage anemia in these patients in a center with established patient blood management and bloodless medicine and surgery programs is feasible and likely to contribute to improved outcome, whereas more studies are needed to better delineate the impact of such programs.

Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample.

BACKGROUND: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful. METHODS AND FINDINGS: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing. CONCLUSIONS: This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME).

BACKGROUND: Severely anemic patients for whom blood transfusion is not an option provide highly valuable information on risks of anemia and alternative management strategies. STUDY DESIGN AND METHODS: This is a retrospective study of consecutive patients at least 18 years old who could not be transfused, had surgery at a patient blood management center between 2003 and 2012, and had at least one hemoglobin (Hb) measurement of not more than 8 g/dL during the postoperative period. The primary outcome measure was mortality, occurring anytime in the period after the surgery until discharge or 30th day after the surgery, whichever was sooner. Postoperative morbidities included the occurrence of any of sepsis, pneumonia, myocardial infarction, deep wound infection, congestive heart failure, and arrhythmia. RESULTS: A total of 293 patients (including 288 who self-identified as "Jehovah's Witness") were eligible and enrolled. The mean ± SD age of the patients was 61.5 ± 16.9 years and 74.1% were female. Overall mortality rate was 8.2% (95% confidence interval [CI], 5%-11.3%). Unadjusted odds ratio (OR) of death per each 1 g/dL decrease in the nadir postoperative Hb was 2.04 (95% CI, 1.52-2.74); OR of death after adjustment for other significant factors (urgency, American Society of Anesthesiology score, and age) was 1.82 (95% CI, 1.27-2.59). CONCLUSION: Our study confirms the previously reported low risk of mortality in upper nadir Hb ranges of 7 to 8 g/dL and much higher risk in lower ranges, albeit the number of patients reaching extremely low Hb levels were lower than previous report, possibly suggestive of improved management strategy of these patients.

Sn doping induced enhancement in the activity of ZnO nanostructures against antibiotic resistant S. aureus bacteria.

Highly ionic metal oxide nanostructures are attractive, not only for their physiochemical properties but also for antibacterial activity. Zinc oxide (ZnO) nanostructures are known to have inhibitory activity against many pathogens but very little is known about doping effects on it. The antibacterial activity of undoped ZnO and tin (Sn) doped ZnO nanostructures synthesized by a simple, versatile, and wet chemical technique have been investigated against Escherichia coli, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa bacterial strains. It has been interestingly observed that Sn doping enhanced the inhibitory activity of ZnO against S. aureus more efficiently than the other two bacterial strains. From cytotoxicity and reactive oxygen species (ROS) production studies it is found that Sn doping concentration in ZnO does not alter the cytotoxicity and ROS production very much. It has also been observed that undoped and Sn doped ZnO nanostructures are biosafe and biocompatible materials towards SH-SY5Y Cells. The observed behavior of ZnO nanostructures with Sn doping is a new way to prevent bacterial infections of S. aureus, especially on skin, when using these nanostructures in creams or lotions in addition to their sunscreen property as an ultraviolet filter. Structural investigations have confirmed the formation of a single phase wurtzite structure of ZnO. The morphology of ZnO nanostructures is found to vary from spherical to rod shaped as a function of Sn doping. The excitation absorption peak of ZnO is observed to have a blue shift, with Sn doping leading toward a significant tuning in band gap.