Hair analysis for Delta9-tetrahydrocannabinolic acid A--new insights into the mechanism of drug incorporation of cannabinoids into hair

Differentiation between external contamination and incorporation of drugs or their metabolites from inside the body via blood, sweat or sebum is a general issue in hair analysis and of high concern when interpreting analytical results. In hair analysis for cannabinoids the most common target is Delta9-tetrahydrocannabinol (THC), sometimes cannabidiol (CBD) and cannabinol (CBN) are determined additionally. After repeated external contamination by cannabis smoke these analytes are known to be found in hair even after performing multiple washing steps. A widely accepted strategy to unequivocally prove active cannabis consumption is the analysis of hair extracts for the oxidative metabolite 11-nor-9-carboxy-THC (THC-COOH). Although the acidic nature of this metabolite suggests a lower rate of incorporation into the hair matrix compared to THC, it is not fully understood up to now why hair concentrations of THC-COOH are generally found to be much lower (mostly <10 pg/mg) than the corresponding THC concentrations. Delta9-Tetrahydrocannabinolic acid A (THCA A) is the preliminary end product of the THC biosynthesis in the cannabis plant. Unlike THC it is non-psychoactive and can be regarded as a 'precursor' of THC being largely decarboxylated when heated or smoked. The presented work shows for the first time that THCA A is not only detectable in blood and urine of cannabis consumers but also in THC positive hair samples. A pilot experiment performed within this study showed that after oral intake of THCA A on a regular basis no relevant incorporation into hair occurred. It can be concluded that THCA A in hair almost exclusively derives from external contamination e.g. by side stream smoke. Elevated temperatures during the analytical procedure, particularly under alkaline conditions, can lead to decarboxylation of THCA A and accordingly increase THC concentrations in hair. Additionally, it has to be kept in mind that in hair samples tested positive for THCA A at least a part of the 'non-artefact' THC probably derives from external contamination as well, because in condensate of cannabis smoke both THC and THCA A are present in relevant amounts. External contamination by side stream smoke could therefore explain the great differences in THC and THC-COOH hair concentrations commonly found in cannabis users.

Effects of cardiology review of the electrocardiogram in patients with suspected acute coronary syndromes

Misclassification of the electrocardiogram (ECG) contributes to treatment errors in patients with acute coronary syndrome. We hypothesized that cardiology ECG review could reduce these errors.

Histological evidence of delayed ischemic brain tissue damage in the rat double-hemorrhage model

The rat double-SAH model is one of the standard models to simulate delayed cerebral vasospasm (CVS) in humans. However, the proof of delayed ischemic brain damage is missing so far. Our objective was, therefore, to determine histological changes in correlation with the development of symptomatic and perfusion weighted imaging (PWI) proven CVS in this animal model. CVS was induced by injection of autologous blood in the cisterna magna of 22 Sprague-Dawley rats. Histological changes were analyzed on day 3 and day 5. Cerebral blood flow (CBF) was assessed by PWI at 3 tesla magnetic resonance (MR) tomography. Neuronal cell count did not differ between sham operated and SAH rats in the hippocampus and the cerebral cortex on day 3. In contrast, on day 5 after SAH the neuronal cell count was significantly reduced in the hippocampus (p<0.001) and the inner cortical layer (p=0.03). The present investigation provides quantitative data on brain tissue damage in association with delayed CVS for the first time in a rat SAH model. Accordingly, our data suggest that the rat double-SAH model may be suitable to mimic delayed ischemic brain damage due to CVS and to investigate the neuroprotective effects of drugs.

Long-term comparison of everolimus-eluting and sirolimus-eluting stents for coronary revascularization

Objectives This study sought to compare the unrestricted use of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention. Background It is unclear whether there are differences in safety and efficacy between EES and SES during long-term follow-up. Methods Using propensity score matching, clinical outcome was compared among 1,342 propensity score–matched pairs of patients treated with EES and SES. The primary outcome was a composite of death, MI, and target vessel revascularization. Results The median follow-up was 1.5 years with a maximum of 3 years. The primary outcome occurred in 14.9% of EES- and 18.0% of SES-treated patients up to 3 years (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.68 to 1.00, p = 0.056). All-cause mortality (6.0% vs. 6.5%, HR: 0.92, 95% CI: 0.68 to 1.25, p = 0.59) was similar, risks of myocardial infarction (MI) (3.3% vs. 5.0%, HR: 0.62, 95% CI: 0.42 to 0.92, p = 0.017), and target vessel revascularization (7.0% vs. 9.6%, HR: 0.75, 95% CI: 0.57 to 0.99, p = 0.039) were lower with EES than SES. Definite stent thrombosis (ST) (HR: 0.30, 95% CI: 0.12 to 0.75, p = 0.01) was less frequent among patients treated with EES. The reduced rate of MI with EES was explained in part by the lower risk of definite ST and the corresponding decrease in events associated with ST (HR: 0.25, 95% CI: 0.08 to 0.75, p = 0.013). Conclusions The unrestricted use of EES appears to be associated with improved clinical long-term outcome compared with SES. Differences in favor of EES are driven in part by a lower risk of MI associated with ST.

Functional parkin promoter polymorphism in Parkinson's disease: new data and meta-analysis

A functional SNP (rs9347683) in the promoter region of the parkin gene had been implicated as a risk factor in older Parkinson's disease (PD) patients.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index. The SWIss Venous ThromboEmbolism Registry (SWIVTER)

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

Cannabis use disorder and age at onset of psychosis--a study in first-episode patients

INTRODUCTION Age at onset of psychosis (AAO) may be younger in patients with cannabis use disorders (CUD) compared to those without CUD (NCUD). Previous studies included CUD co-morbid with other substance use disorders (SUD), and many did not control for confounders. METHODS Controlling for relevant confounders, differences in AAO between patients with and without CUD excluding those with any other SUD were analyzed in a large representative file audit of 625 first-episode psychosis (FEP) patients (age 14 to 29years) admitted to the Early Psychosis Prevention and Intervention Centre in Melbourne, Australia. RESULTS Three quarters of the 625 FEP patients had a CUD. Cannabis use started before psychosis onset in 87.6% of patients. AAO was not significantly different between CUD (without other SUD, n=201) and NCUD (n=157). However, AAO was younger in those with early CUD (starting age 14 or younger) compared to NCUD (F(1)=5.2; p=0.024; partial η(2)=0.026). Earlier age at onset of cannabis use predicted earlier age at onset of psychosis (β=-0.49, R(2)-change=0.25, p<0.001). CONCLUSION Only CUD starting age 14 or younger was associated with an earlier AAO at a small effect size. These findings suggest that CUD may exert an indirect effect on brain maturation resulting in earlier AAO potentially only in cannabis sensitive subjects.

Effects and limitations of an AED with audiovisual feedback for cardiopulmonary resuscitation: a randomized manikin study

Correctly performed basic life support (BLS) and early defibrillation are the most effective measures to treat sudden cardiac arrest. Audiovisual feedback improves BLS. Automated external defibrillators (AED) with feedback technology may play an important role in improving CPR quality. The aim of this simulation study was to investigate if an AED with audiovisual feedback improves CPR parameters during standard BLS performed by trained laypersons.