Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC–MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150 mg, caffeine 75 mg, and propyphenazone 375 mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5 ng/mg and 56.0 ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45 ng/mg and 11.1 ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC–MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective

Impact of continuing or quitting smoking on episodic cluster headache: a pilot survey

Abstract BACKGROUND: The majority of patients suffering from cluster headache (CH) are smokers and it has been suggested that smoking may trigger the development of CH. The aim of this pilot survey was to describe: 1. the differences between current, former, and never smokers CH patients; 2. if smoking changed during an active cluster period; 3. if CH changed after quitting. METHODS: All outpatients with episodic CH according to the criteria of ICHD-II who were consecutively seen for the first time from October 2010 to April 2012 at a headache centre were interviewed by phone using a specifically prepared questionnaire. Statistical differences between continuous variables were analysed by the Student's t-test or the one-way analysis of variance (ANOVA), followed by Newman-Keuls post-hoc testing. Comparisons between percentages were made using the Chi-square test or Fisher's exact test. All data were expressed as the mean ± standard deviation (SD). RESULTS: Among a total of 200 patients surveyed (172 males, 28 females; mean age ± SD: 48.41 ± 12 years) there were 60%, 21%, and 19% of current, former, and never smokers, respectively. Current smokers reported longer active periods (12.38 ± 10 weeks) and a higher maximum number of attacks per day (3.38 ± 1) compared to never smoker CH patients (5.68 ± 4 weeks, P <0.05 and 2.47 ± 1, P <0.05, respectively). During the active period most of the patients stated to decrease (45.7%) or not to change (45.7%) the number of cigarettes smoked. Among those who decreased smoking, most (83.8%) reported that they had less desire to smoke. After quitting, the majority of former smokers stated that their headache had not changed. CONCLUSIONS: Patients with episodic CH who are also smokers appear to have a more severe form of the disorder. However, it is unlikely that between CH and smoking there is a causal relationship, as CH patients rarely improve quitting smoking

Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

BACKGROUND: Medication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inflammatory drugs (NSAIDs), triptans and mixtures abusers, in comparison with non-abusers individuals (controls). METHODS: In the present work we employed specialized proteomic techniques, namely two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS), and the innovative Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry (SELDI-TOF-MS), to discover characteristic proteomic profiles associated with MOH condition. RESULTS: By 2-DE and MS analysis we identified 21 over-excreted proteins in MOH patients, particularly in NSAIDs abusers, and the majority of these proteins were involved in a variety of renal impairments, as resulted from a literature search. Urine protein profiles generated by SELDI-TOF-MS analysis showed different spectra among groups. Moreover, significantly higher number of total protein spots and protein peaks were detected in NSAIDs and mixtures abusers. CONCLUSIONS: These findings confirm the presence of alterations in proteins excretion in MOH patients. Analysis of urinary proteins by powerful proteomic technologies could lead to the discovery of early candidate biomarkers, that might allow to identify MOH patients prone to develop potential drug overuse-induced nephrotoxicity

Fecal microbiota transplantation to improve efficacy of immune checkpoint inhibitors in renal cell carcinoma (TACITO trial)

Background: Renal cell carcinoma (RCC) is the 6° most common cancer in men and the 8° in women in the USA. In Italy RCC incidence was 11,500 new cases in 2017, while mortality was 3,371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel treatment option aimed to restore healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection. Preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of this study is to evaluate, through a double-blinded placebo-controlled randomized clinical trial, the efficacy of targeted FMT (from donors who are responding to ICIs) in improving response rates to ICIs in subjects with aRCC. Methods: 50 patients who are about to receive, or have started by &lt;8 weeks, pembrolizumab + axitinib as first-line therapy for aRCC will be enrolled. Exclusion criteria include major comorbidities, concomitant GI or autoimmune disorders, or HIV, HBV, HCV infection, continuative corticosteroid therapy, previous treatment with systemic immune-suppressants or immune-modulatory drugs, antibiotic therapy within 4 weeks prior to enrollment. Stool samples and clinical data will be collected at baseline. Then, patients will be randomized to donor FMT or placebo FMT. They will receive the first infusion by colonoscopy and then oral frozen fecal or placebo capsules (8 capsules t.i.d.) 90 and 180 days after the first FMT. Stool donors will be searched among long-term (&gt;12 months) responders to ICIs, and will be selected by following protocols recommended by international guidelines. Patients in the FMT group will always receive feces from the same donor throughout the three fecal transplants. Frozen fecal batches and frozen fecal capsules will be manufactured according to international guidelines. Patients will be followed-up 7, 15, 30, 90, 180, 270, and 360 days after randomization for clinical evaluation and collection of stool samples. Patients will also undergo radiological assessment at 90, 180, 270 and 360 days after randomization. Microbiome analysis will be performed with shotgun metagenomics. The primary endpoint is the progression-free survival (PFS) at 12 months. Secondary endpoints are: objective response rate at 12 months; overall survival at 12 months; adverse events after FMT; microbiome changes after FMT. Sample size calculation was based on the hypothesis that FMT can improve the 1-year PFS rate from 60% (reported 1-year PFS for SOC) to 80% wen associated to SOC. Clinical trial information: NCT04758507

Smell and 3D Haptic Representation: A Common Pathway to Understand Brain Dynamics in a Cross-Modal Task. A Pilot OERP and fNIRS Study

Cross-modal perception allows olfactory information to integrate with other sensory modalities. Olfactory representations are processed by multisensory cortical pathways, where the aspects related to the haptic sensations are integrated. This complex reality allows the development of an integrated perception, where olfactory aspects compete with haptic and/or trigeminal activations. It is assumed that this integration involves both perceptive electrophysiological and metabolic/hemodynamic aspects, but there are no studies evaluating these activations in parallel. The aim of this study was to investigate brain dynamics during a cross-modal olfactory and haptic attention task, preceded by an exploratory session. The assessment of cross-modal dynamics was conducted through simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) recording, evaluating both electrophysiological and hemodynamic activities. The study consisted of two experimental sessions and was conducted with a sample of ten healthy subjects (mean age 25 5.2 years). In Session 1, the subjects were trained to manipulate 3D haptic models (HC) and to smell different scents (SC). In Session 2, the subjects were tested during an attentive olfactory task, in order to investigate the olfactory event-related potentials (OERP) N1 and late positive component (LPC), and EEG rhythms associated with fNIRS components (oxy- Hb and deoxy-Hb). The main results of this study highlighted, in Task 1, a higher fNIRS oxy-Hb response during SC and a positive correlation with the delta rhythm in the central and parietal EEG region of interest. In Session 2, the N1 OERP highlighted a greater amplitude in SC. A negative correlation was found in HC for the deoxy-Hb parietal with frontal and central N1, and for the oxy-Hb frontal with N1 in the frontal, central and parietal regions of interests (ROIs). A negative correlation was found in parietal LPC amplitude with central deoxy-Hb. The data suggest that cross-modal valence modifies the attentional olfactory response and that the dorsal cortical/metabolic pathways are involved in these responses. This can be considered as an important starting point for understanding integrated cognition, as the subject could perceive in an ecological context

The State-Trait Anxiety Inventory: Shadows and Lights on its Construct Validity

Abstract Past studies on the factor validity of the Trait subscale of the Spielberger’s State-Trait Anxiety Inventory (STAI-T) do unanimously agree on its structure. In fact, researchers are still debating whether the STAI-T is unidimensional or multidimensional. Our aim was to clarify what the STAI-T measures. The STAI-T, the Beck Depression Inventory–II, the Teate Depression Inventory, and the Beck Anxiety Inventory were administered to 1124 psychiatric outpatients and to 877 healthy subjects. A confirmatory factor analysis was performed in order to compare various models in the literature. The internal consistency and convergent and discriminant validity of the STAI-T as well as its factorial subscales were assessed. The one-construct two-method (i.e., the STAI-T measures one substantive anxiety construct plus artifacts due to negative–positive item polarity) and the bifactor (i.e., the STAI-T comprises two first-order specific factors [“Anxiety” and “Depression”] and one first-order general factor) models were the best-fitting solutions for the STAI–T in both the clinical and nonclinical samples. The STAI–T total score correlated more strongly with measures of depression than with a concurrent measure of anxiety. The STAI-T should be considered a measure of general negative affect, including specific aspects of cognitive anxiety and depression together. Keywords Confirmatory factor analysis . Psychological tests . Anxiety . Depression . Reliability and validit

Obstructive sleep apnea syndrome and olfactory perception: An OERP study

Obstructive Sleep Apnea Syndrome (OSA) is characterized by snoring associated with repeated apnea and/or obstructive hypopnea. The nasal airways of OSA patients, measured via acoustic rhinometry, could be significantly narrower than healthy subjects and this reduced nasal structure can impair olfactory function. The relationship between nasal structure and olfactory function, assessed via behavioral test results, indicates that there is a high prevalence of nasal airflow problems. Based on these assumptions, the purpose of this study was to carry out an assessment of olfactory perception in OSA patients through the Chemosensory Event-Related Potentials (CSERP), investigating the N1 component and the Late Positive Component (LPC). Twelve OSA patients, non-smokers, were recruited in the Pulmonary Rehabilitation Unit, scored with the Epworth Sleepiness Scales, after Polygraphic Recording, Apnea Hypopnea Index and Body Mass Index evaluation. The control group consisted of twelve healthy controls, non-smokers, recruited as volunteers. Subjects, during an EEG recording, performed an oddball olfactory recognition task based on two scents: rose and eucalyptus. Main results highlighted differences in N1 and LPC between OSA and controls. OSA patients presented faster N1 latencies and greater amplitude. The same trend was found in LPC, where OSA showed decreased latency and increased amplitude during rose stimulation, in the right inferior frontal cortex. and faster latencies in left centroparietal cortex OERP results can suggest an impairment in endogenous components. This result could be the consequence of the exogenous perceptual difficulty highlighted in N1 component. The increased arousal could also be related to the respiratory activity involved during the olfactory task