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Hair testing as a marker of adherence to headache treatments
Background
Medication adherence has a critical importance in the therapy of primary headaches, both to gain pain relief and improving patients’ quality of life. Nowadays, hair is a fundamental biological specimen, alternative to the usual samples like blood and urine, to monitor adherence to pharmacological treatments: it is uninvasive and it can detect many drugs simultaneously with a detection window of many months. Therefore, in order to understandt if hair analysis should be useful to document headache patients’ adherence to chronic treatments, we analysed the detection rate of 23 therapeutic drugs in the hair of headache patients, the degree of agreement between self-reported drug and type of drug found in hair, whether the concentrations measured in hair reflected the drug doses that the patients had reported to have taken in the previous 3-month period.
Methods
93 headache patients (mean age ± SD: 48.13 ± 12.03 years; females 94%) were enrolled.
All these patients declared a chronic assumption, for at least 3 months, for headache prophylaxis or for their psychiatric comorbidities, with at least one of the following 23 drugs: alprazolam clonazepam, delorazepam diazepam, flurazepam, lorazepam, lormetazepam, triazolam, zolpidem, amitriptyline, clomipramine, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, mirtazapine, trazodone, levomepromazine, levosulpiride, quetiapine e topiramate.
This study was approved by the Provincial Ethical Committee of Modena and every patient gave a free-informed consent to participate the study.
A detailed pharmacological history and hair sample (7 mm diameter and 4 cm of lenght) was collected for each patient. Hair samples were analysed by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) by a method that we developed. Statistical analysis was performed with the StataIC 13 software.
Results
All the previous 23 drugs were detected in hair samples of patients who declared them. In particular, 82% of the declared drugs were found in the 100% of samples. Negative results for the declared drugs were only 9. The agreement between type of self-reported drug and type of drug found in hair was excellent for all drugs (P<0.01, Cohen’s kappa). The relationship between the last 3 months cumulative dose and hair concentration was statistically significantly (P<0.05, linear regression analysis) for delorazepam, lorazepam, amitriptyline, citalopram, duloxetine, venlafaxine and for its metabolite, desvenlafaxine.
Conclusion
Hair appears to be a unique matrix to monitor chronic drug use in headache patients. Drugs hair concentrations are a reliable marker of adherence to headache pharmacological treatments
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
A study of distribution of ethyl glucuronide in post-mortem matrices
Background and aim. Ethanol determination in post-mortem blood is one of the most important and frequently requested analysis in legal medicine and forensic toxicology. Post-mortem ethanol formation is a well-known problem, so correct interpretation of ethanol detection in post-mortem samples can be difficult. Therefore determining whether a finding of ethanol is due to antemortem ingestion of alcohol or not is very relevant in order to solve medico-legal question regarding traffic or occupational accidents or to establish victime capacity of reaction. EtG is a non oxidative ethanol metabolite with many applications in forensic toxicology. In autopsy samples can be used to determine recent alcohol consumption if blood ethanol has already been eliminated (that explains for example a positivity to cocaetilene [CE]) but furthermore it is a marker of antemortem ethanol ingestion. Study aim was to investigate the EtG distribution in post-mortem matrices: EtG concentration in heart blood, femoral blood and liver has been determined by LC-MS/MS.
Material and methods. The samples were collected in autopsies of the Institute of Legal Medicine in Modena, Italy. We selected blood ethanol positive or blood CE positive autopsy cases in the period 2012-2015, during which all autopsy were also analyzed for EtG. In all cases we also recorded time frame between death and autopsy, case history, cause of death, putrefaction, if present. The analytical method used allowed the quantification of EtG in postmortem blood and liver. Among sample preparation, 200 mg of blood and 1 g of liver were added with physiological water, 200 mg supernatant was added to 10 μL internal standard solution (EtG-D5 1 ng/μL), 900 μL methanol. The methanol layer was transferred to Phenomenex PhreeTM Phospholipid Removal Tabbed 1 ml Tube. The cleaned methanol solution was taken to dryness and analysed by LC-MS/MS with negative ionization MRM mode.
Results and discussion. We analized 54 autopsy cases and in total 113 autopsy samples. The frame between death and autopsy ranged from 24 h to 9 days. Both heart blood and peripheral blood was obtained in 31 cases, in 28 cases also liver speciman was available, in 21 cases only central blood was obtained, in 2 cases only peripheral blood. In 41 cases EtG was positive. In these EtG positive cases heart blood concentrations ranged from 10 to 42000 ng/ml, femoral blood concentraion ranged from 10 to 4698 ng/ml, liver concentrations ranged from 394 to 40615 ng/g. Distribution data of EtG in tested specimens will be presented
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Diagnostic accuracy of hair analysis for the detection of triptan overuse in migraineurs
Prescription drugs abuse is an important cause of mortality, morbidity, and healthcare expenditure worldwide. Chronic migraineurs frequently overuse triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan), which are selective 5-HT1B-D agonists and specific anti-migraine drugs. Routine methods to monitor triptan overuse in clinical settings are currently lacking. The aim of this study is to assess the accuracy of hair analysis in detecting triptan overuse.
One hundred and fifty migraineurs were diagnosed as triptan overusers or occasionally users according to the criteria of The International Classification of Headache Disorders, 3rd edition (beta version), calculating the doses of triptans taken in the last 3 months from the headache diary. For every patient a nuchal hair sample was collected and 3 centimetres-long proximal section was analysed by LC-MS/MS with a validated method. The accuracy of hair analysis in detecting triptan overuse was analysed with receiver operating characteristic (ROC) curve analysis; the cut-off of hair concentrations discriminating overusers from occasionally users were determined with Liu's method.
The accuracy of hair analysis in distinguishing occasionally users from overusers was high for almotriptan (ROC AUC = 0.9013), eletriptan (ROC AUC = 0.8305), rizatriptan (ROC AUC = 0.9250) and sumatriptan (ROC AUC = 0.9015). The cut-off of hair concentrations discriminating overusers from occasionally users were: 526 pg/mg for almotriptan (sensitivity = 77%, specificity = 96%), 789 pg/mg for eletriptan (sensitivity = 83%, specificity = 75%), 179 pg/mg for rizatriptan (sensitivity = 88%, specificity = 95%) and 139 pg/mg for sumatriptan (sensitivity = 83%, specificity = 91%). Hair analysis is an accurate method to discriminate between occasional and triptan overuse
Tramadol chronic abuse: An evidence from hair analysis by LC tandem MS
Hair analysis, as complementary matrix, has expanded across the spectrum of toxicological investigations for misuse drug monitoring. Hair has become an important matrix for drug analysis, owing to the possibility to detect target analytes for long time periods, depending on hair length. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitation of tramadol, a widely used centrally-acting analgesic, and its main metabolites in hair (ODMT, NDMT, NOT). Hair samples were decontaminated and incubated overnight in diluted hydrochloric acid; the extracts were purified by mixed-mode solid phase cartridges and analyzed by LC-MS/MS in positive ionization mode monitoring two transitions per analyte. The procedure was fully validated in terms of linearity, limit of detection and lower limit of quantitation (LLOQ), accuracy, precision, recovery, matrix effect and selectivity. The linear regression analysis was calibrated by deuterated internal standards; for all analytes, responses were linear over the range 0.04-40.00 ng/mg hair, with R2 values of at least 0.995. The method offered satisfactory precision (RSD < 10%), accuracy (90-110%) and recovery (>90%) values. The found LLOQ values for tramadol and metabolites were in the range 0.010-0.030 ng/mg hair. The proposed procedure was successfully applied to quantify tramadol and metabolites in real hair samples submitted to our laboratory: three cases of tramadol assumption within the therapeutic dosage (3 x 2 segments) and one case of tramadol abuse in a binge pattern (8 segments). The ranges found for TRAM, ODMT, NDMT and NOT were markedly higher in the abuse case (63.42-107.30, 3.76-6.26, 24.88-45.66, 0.22-1.18 ng/mg hair, respectively) compared to the other case reports (3.29-20.12, 0.28-1.87, 0.45-4.32, 0.07-0.80 ng/mg, respectively); also the values of NMDT/ODMT ratio differed significantly. According to the obtained data, we hypothesized that the binge pattern may influence the metabolites' to parent drug concentration ratios; therefore this parameter could represent a target assessment tool to monitor abuse cases
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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