Alessio Gili

Norcocaine and cocaethylene distribution patterns in hair samples from light, moderate, and heavy cocaine users.

Even though hair analysis often seems to be the best choice for retrospective monitoring of cocaine intake, differentiating between incorporated cocaine and external contamination is widely debated. In this study we report results obtained in 90 hair samples from addicts. All samples were analyzed for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by gas chromatography‐mass spectrometry (GC‐MS) techniques coupled with direct immersion solid‐phase micro‐extraction. Cocaine concentrations were stratified into three classes of usage: light (0.5–3 ng/mg), moderate (3.1–10 ng/mg) and heavy (10.1–40 ng/mg). The Substance Abuse and Mental Health Services Administration cut‐off criteria for establishing active cocaine use were applied to the results. For all samples criteria were cocaine levels above 0.5 ng/mg (ranging from 1.63 to 39.29 ng/mg, mean 9.49 ng/mg), benzoylecgonine concentrations ≥ 0.05 ng/mg (ranging from 0.19 to 5.77 ng/mg, mean 1.40), and benzoylecgonine to cocaine % ratio ≥5% (from 6.43 to 26.09%). Norcocaine was present in 58.9% of samples (concentration range: 0.22–3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations above 9.58 ng/mg). Twenty hair samples from moderate and heavy users tested positive for cocaethylene (concentration range: 0.22–1.98 ng/mg, mean 0.73 ng/mg). This study on hair samples with no chance of false positive cases highlights the very limited applications of testing minor cocaine metabolites for definitive proof of active cocaine consumption.

Cuff pressure monitoring by manual palpation in intubated patients: How accurate is it? A manikin simulation study

BACKGROUND Endotracheal intubation (ETI) for mechanical ventilation has a central role in the Intensive Care Unit (ICU). ETI is one of the main risk factors for the development of ventilator-associated pneumonia (VAP) as its presence reduces the natural defences of the upper airway and allows the micro-suction of secretions in the airways. In order to minimise such complications, it is fundamental to maintain a suitable pressure inside the tube cuff. AIM AND SCOPE The main objective of the present study is to evaluate the effectiveness and reliability of palpation method, performed with the operators fingers, for detecting the tube cuff pressure. RESULTS The study was performed using a manikin to test the pressure of the ETT cuff, on a sample constituted by nurses employed in three Italian ICU from two different Umbrian hospitals. From a total of 68 participants, detection by palpation method revealed to be not correct in 68% of cases; in particular, only 10% of respondents can correctly detect a pressure in the recommended range (20-30cmH2O) using palpation. Moreover it was possible to highlight that the participation in emergency courses has a positive effect on the correct measurement of cuff pressure using the palpation method (V=0.501). CONCLUSIONS The study, in agreement with the literature, confirms the thesis that the palpation method is inadequate to determine an estimate of the pressure existing inside the cuff.

The impact of overdiagnosis on thyroid cancer epidemic in Italy,1998–2012

AIMS In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attributable to overdiagnosis. METHODS Data on TC cases reported to Italian cancer registries during 1998-2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region. RESULTS In Italy between 1998-2002 and 2008-2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998-2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008-2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders. CONCLUSION(S) Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.

Pain assessment in the Emergency Department. Correlation between pain rated by the patient and by the nurse. An observational study

Background and aim of the study: Pain is always present in the Emergency Department (ED), but is often underestimated. The primary purpose of this study is to analyze the degree to which the intensity of pain is underestimated or overestimated in the perception of the nurse and the patient in the ED. The secondary objective of this research is to study possible factors that lead to these discrepancies in assessment. Methods: The observational study was carried out in two Hospitals in Central Italy. The sample population was based on 130 patients and 26 nurses. A questionnaire was given to the patients who provided personal data followed by information regarding their pain, including an assessment of the intensity of pain on a scale from 0 to 10. A similar questionnaire was given to the nurses. Results: The average score based on the numeric rating scale (NRS) to assess the intensity of pain perceived by the patients is 6.16, while the numerical average estimated by the nurses based on their assessment is 5. Using the t test we found that the average between nurse and patient assessments was very significant. The analysis of the nurses’ characteristics and professional experiences, age, years of employment and years of service in the ED are all significant variables affecting the discrepancy between the nurses’ and patients’ assessments of pain. As previous studies have shown, nurses tend to underestimate the degree of pain. In fact, in only 55.5% of the cases was there a correspondence in the evaluations of the intensity of pain done by nurses and patients, and in no case did the nurses’ evaluation exceed that of the patients. Conclusions: This study reveals the persistent difficulty in pain management, while attempting contemporaneously to communicate the importance of the assessment, since adequate understanding of pain renders it possible to recognize and treat it.

Could thymomectomy be a reasonable option for non-myasthenic thymoma patients?

Background Complete resection is the mainstay of treatment for thymoma, but few studies have investigated the extent of resection on normal thymus. Extended thymectomy is considered the treatment of choice for myasthenic patients with thymoma, while the optimal therapy for non-myasthenic patients is still a matter of debate. The aim of this retrospective study was to compare extended thymectomy vs. thymomectomy in non-myasthenic thymoma patients for (I) oncological outcome, (II) multicentric thymoma occurrence and (III) postoperative myasthenia gravis (MG) development. Methods A retrospective comparative study was conducted on 92 non-myasthenic patients with completely resected thymoma, according to the extent of resection: extended thymectomy (70 patients) vs. R0-mediastinal thymomectomy (22 patients). Clinical and pathological characteristics, oncological outcome and postoperative MG occurrence were compared between the two study groups. Results We did not observe any significant differences in gender, age, symptomology, preoperative chemotherapy, histology, tumour size, adjuvant therapy or complications. There were no recorded postoperative mortalities. Stage distribution was different between the two groups: similar percentages of early stage thymoma for both groups were present, but there was a prevalence of stage III for extended thymectomy and stage IV for thymomectomy (P<0.01). At a median follow-up of 77.4 months (range 1-255 months), no statistically significant differences were recorded in local recurrence (P=0.396), thymoma related deaths (P=0.504), multicentric thymoma occurrence (P=0.742) and postoperative MG development (P=0.343). A high preoperative anti-acetylcholine receptor antibodies (ARAb) serum titer assay was statistically correlated with postoperative MG occurrence (r=0.49, P<0.05). Conclusions Thymomectomy appears to be a valid treatment option for non-myasthenic thymoma patients, as this procedure was associated to the same 5-year oncological results, compared to extended thymectomy, for both stage I-II small thymomas and patients with giant unilateral masses, as well as advanced diseases. Moreover, thymomectomy was not associated to an increased rate of postoperative MG.

Monitoring people at risk of drinking by a rapid urinary ethyl glucuronide test

Abstract Alcohol and illicit drug abuse are major public health problems worldwide. Since alcohol is the predominant substance of choice in polydrug abusers, monitoring its use, along with urinary drug screening in patients in rehabilitation programs, appeared to be crucial in identifying patients at risk of alcohol disorders leading to impaired quality of life. Ethyl β-D-6-glucuronide, a non-oxidative, non-volatile, stable and minor direct ethanol metabolite, has a 6h to 4 day window of detection in urine after the last alcohol intake. Each of the 119 subjects (85 males, 34 females) registered with the Public Health Service for Drug Dependence Treatment provided a urine sample for ethylglucoronide (EtG) determination in an immunochemical test with a 500 ng/ml cutoff. All results were evaluated with confirmation criteria of a fully validated gas chromatography/mass spectrometry assay. The diagnostic performance of the EtG immunochemical test was assessed using Receiver Operating Characteristic Curve analysis. The immunochemical test specificity was 100% for EtG urinary values above 500 ng/ml. No false positive results were found. With levels below 500 ng/ml, 12% of the samples were classified as negative. The average consumption of the incorrectly classified subjects was 171 ng/ml, with a misclassification error of 6.5% to 18.5%. High agreement between EtG as determined in an immunochemical test and gas chromatography/mass spectrometry, suggests that the rapid EtG test is a reliable, cost-effective alcohol monitoring assay for patient management in many non-forensic settings, such as drug rehabilitation programs.

Targeting EGFR and ALK in NSCLC: current evidence and future perspective

The advent of molecular therapy targeting specific driver oncogenes has dramatically changed the prognosis of a subset of NSCLC, dilating survival and improving the quality of life of patients with advanced disease. Two of the major targets for treatment with receptor TKIs are the activated mutated forms of the EGFR and the ALK gene fusions. In advanced NSCLC patients harboring EGFR mutations or ALK rearrangements, the use of TKIs in the first-line setting, have provided unexpected large progression-free survival and overall survival benefits, compared with cytotoxic chemotherapy. However, despite initial responses and durable remissions, the development of resistance inevitably leads to treatment failure. The aim of this review is to discuss the treatment strategy currently used for tumors harboring these two genetic targets and to focus on what will be available in clinical practice in the near future.