Opto-magnetic imaging spectroscopy in analyzing rotary NiTi endodontic instruments.

Intra-canal fracture of rotary NiTi instruments occurs due to torsional stress, cyclic fatigue, or a combination of these two factors. Broken instruments are a serious obstacle to shaping, cleaning, and filling of the root canal and can adversely affect the outcome of endodontic therapy. The aim of this study was to examine the magnetic properties and ultrastructural changes of new, used, and fractured NiTi instruments using opto-magnetic imaging spectroscopy (OMIS). The study included three sets of different types of rotary instruments: MTwo (VDW, Munich, Germany), Pro Taper Universal (Dentsply Maillefer, Ballaigues, Switzerland), and BioRace (FKG DENTAIRE Swiss Dental Products, Le Crêt-du-Locle Switzerland). Root canal shaping was performed on root canals with different curvatures, and after intra-canal fracture, instruments of the same type (new, used, and fractured) were analyzed using OMIS at the Faculty of Mechanical Engineering, University of Belgrade. The obtained results showed a coincidence of peak localization for the used instruments that did not suffer a fracture, as well as for new, unused instruments of all examined groups. Additionally, there was a coincidence of peak intensities for new and fractured instruments in all groups. The specific treatment of electropolishing of the active surface of BioRace instruments caused a completely different electromagnetic response compared to conventional NiTi sets of tested instruments. New, unused BioRace instruments had the most pronounced positive (5.6078 n.a.u. x1000) and negative (-8.5218 n.a.u. x1000) intensity values. The analysis of NiTi instruments using opto-magnetic imaging spectroscopy indicated changes in the magnetic properties after their instrumentation.

Awareness of Prostate Cancer among the Sportsmen in the Republic of Serbia.

Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population.

Opto-magnetic imaging spectroscopy in characterization of the tissues during hyperbaric oxygen therapy.

BACKGROUND/AIM: Opto-magnetic imaging spectroscopy (OMIS) was used as a novel method to detemine tissue molecular conformation changes during hyperbaric oxygen (HBO) therapy. The aim of this study was to examine the usefulness of OMIS for the assessment of HBO therapy effectiveness on the diseased tissue. METHODS: OMIS is concerned with obtaining paramagnetic/diamagnetic properties of materials, related to the presence of unpaired/paired electrons based on their interaction with visible light. The basic tool is light of wavelength in the range between 400 nm and 700 nm and its interaction with tissue. The study included 22 subjects: 16 angiopathy patients and 6 healthy subjects as the control group. OMIS was used with patients on the 1st, 10th and 20th session and with the control group on the 1st, 10th and 20th day without HBO therapy in between. RESULTS: The obtained results showed that healthy skin of all the control group subjects had the same shape curve. In the angiopathy patient group, before the first session OMIS showed tissue disorder and after the last session results resembled more closely the results in healthy tissue. The differences in the tissue state in the angiopathy group before each session were noticeable, showing normalized tissue under the influence of HBO. CONCLUSION: The results show that OMIS could be used as a diagnostic tool for detection of the tissue state before and after the HBO therapy.

Potential cost-effectiveness of therapeutic drug monitoring for depressed patients treated with citalopram.

BACKGROUND: For patients treated with citalopram, it was recently shown that serum concentrations above 50 ng/mL on day 7 of treatment are associated with an improved therapeutic outcome. The aim of this post hoc analysis was to calculate a potential cost-effectiveness of therapeutic drug monitoring (TDM) considering costs for hospitalization, medication, and drug analysis. METHODS: The study included patients with major depression. Weekly measurements of serum concentrations and assessments of psychopathology were conducted. RESULTS: Fifty-five patients were included in this analysis. For patients with high citalopram serum concentrations (>50 ng/mL), the mean duration of hospitalization was 49 ± 20 days, and it was 72 ± 37 days (P = 0.03) in the group with low drug concentrations (<50 ng/mL). Considering daily costs for hospitalization of 250€,;, the potential savings amounted to 5750€,; per patient for the 23 days. Assuming that 11% of the variation of duration of hospitalization per patient were attributed to the serum concentration of the drug, the resulting savings were 633€,; per patient. Considering the officially listed price of 21€,; per TDM assay, total costs for weekly measurements over a period of 10 weeks of hospitalization were 210€,;. In the groups with high and low serum concentrations, daily costs for citalopram medication were 3.00 ± 0.80€,; and 2.42 ± 0.70€,;, respectively (P = 0.002), and the mean number of comedications was nearly identical, that is, 1.87 ± 1.74 and 1.81 ± 1.86 drugs, respectively (P = 0.919). CONCLUSIONS: The data taken together indicate that TDM-guided dosing of citalopram has the potential to be cost effective by reducing the length of hospitalization.

Association between citalopram serum levels and clinical improvement of patients with major depression.

Imaging studies have shown that serum concentrations of the selective serotonin reuptake inhibitor citalopram correlate with serotonin transporter (5-HTT) occupancy in vivo. In patients with major depressive disorders treated with citalopram, 80% 5-HTT occupancy was considered to be necessary for maximal therapeutic effects, which requires citalopram serum concentrations of at least 50 ng/mL. The aim of this study was to compare treatment outcome in patients with citalopram serum concentrations greater than and less than 50 ng/mL after 7 days of treatment. This study included inpatients with acute major depressive disorder according to International Classification of Disease, 10th Revision who were treated with citalopram. In weekly intervals, the severity of depression was assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17), and serum concentrations of citalopram were measured from baseline until week 5. Fifty-five patients were eligible for this analysis. After 7 days of treatment, 19 patients showed citalopram serum concentrations of 50 ng/mL or greater; 36 patients had lower concentrations. Patients at greater than the 50-ng/mL threshold had (i) lower mean HAMD-17 sum scores from day 7 to end point (P ≤ 0.018 for each analysis); (ii) a more pronounced HAMD-17 decrease (P ≤ 0.019 for each analysis), and (iii) 23 days' shorter duration of hospitalization (P = 0.033) than patients with levels of citalopram less than 50 ng/mL. As regards adverse effects, both patient groups were not significantly different. Despite therapeutic doses, a significant number of patients had serum concentrations less than 50 ng/mL, and these were associated with an unfavorable treatment outcome; therapeutic drug monitoring is recommended to optimize dosing citalopram in the early phase of treatment.

Population pharmacokinetic analysis of mirtazapine.

OBJECTIVE: Mirtazapine belongs to the new generation of antidepressants that is commonly used in clinical routine. Therefore, we feel it mandatory to control compliance in the context of non-response, adverse events or other clinical situations by means of plasma concentration measurements. While controlled clinical studies have evaluated the effect of individual covariates on the pharmacokinetics of mirtazapine, our analysis aims to identify covariates within a naturalistic clinical setting. METHODS: We performed non-linear mixed-effects modelling with data from 65 depressed inpatients whose plasma concentrations were measured weekly during their stay in hospital. Each patient's age, height, weight, co-medication, alcohol, coffee and cigarette consumption, weekly serum creatinine concentrations, liver enzyme activity, blood pressure and pulse was noted. From 49 patients, the genotype of cytochrome P450 (CYP) isoenzymes 2D6, 2C9 and 2C19 was analysed. RESULTS: The clearance of CYP2D6 intermediate metabolisers was reduced by 26% compared with extensive metabolisers. No other factor significantly influenced the clearance of these patients. CONCLUSION: The variability of mirtazapine plasma concentrations in clinical routine is caused to a relevant degree by CYP2D6. This should be taken into account when therapeutic drug monitoring is carried out to check treatment adherence or when a special clinical situation, such as co-morbidity and add-on medication, demands careful dosing of this drug.

Therapeutic monitoring of new antipsychotic drugs.

Typical antipsychotic drugs qualify for therapeutic drug monitoring (TDM) primarily for the following reasons: control of compliance and avoidance of extrapyramidal side effects by keeping chronic exposure to minimal effective blood levels. For the atypical antipsychotic clozapine, drug safety is another reason to use TDM. With regard to the new antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole, which have been introduced in the clinic during the last few years, the rationale to use TDM is a matter of debate. Positron emission tomography (PET), which enables measurement of the occupancy of dopamine D2 receptors, revealed that receptor occupancy correlated better with plasma concentrations than with doses of the antipsychotics. Regarding plasma levels related to therapeutic effects, optimal concentrations have been established for clozapine (350-600 ng/mL), risperidone (20-60 ng/mL), and olanzapine (20-80 ng/mL) but not for the other new antipsychotics. Studies that included analyses of drug levels in blood reported mean concentrations of 68 ng/mL for quetiapine and 317 ng/mL for amisulpride under therapeutic doses of the antipsychotic drugs. For ziprasidone or aripriprazole, data on therapeutic drug concentrations are so far lacking. In conclusion, evidence is growing that TDM may improve efficacy and safety in patients treated with the new antipsychotic drugs, especially when patients do not respond or develop side effects under therapeutic doses. The few reported investigations, however, need to be confirmed and extended.

Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting.

OBJECTIVE: This evaluation focuses on polymorphisms of the cytochrome-P450 (CYP) isoenzymes 2C9, 2C19 and 2D6 and their association with plasma concentrations within a typical clinical setting. Side effects and treatment response were analysed in an exploratory approach in poor and ultra-rapid metabolisers. PATIENTS AND METHODS: We analysed 136 Caucasian depressed inpatients treated with amitriptyline, citalopram, clomipramine, doxepin, fluvoxamine, mirtazapine, paroxetine, sertraline and venlafaxine, who underwent weekly plasma concentration measurements, assessment of the severity of illness and side effects during their stay in the hospital. Patients were genotyped with respect to CYP2C9 alleles *1 and *2, the CYP2C19 alleles *1, *2 and *3 and the CYP2D6 alleles *1 to *9 and CYP2D6 gene duplication. RESULTS: CYP2D6 poor metaboliser genotype and co-medication with inhibitors of CYP2D6 were associated with higher plasma concentrations than the drug-specific median plasma concentration when normalised to dose; plasma concentrations of CYP2C19 extensive metabolisers and smokers were significantly lower than the drug-specific median. Five of the six CYP2D6 poor metabolisers experienced side effects. Response was not associated with plasma concentrations above or below the lower limit of a presumed therapeutic range. CONCLUSION: These data indicate a significant influence of the CYP2D6 genotype, minor influence of the CYP2C19 genotype and no influence of the CYP2C9 genotype on plasma concentrations of patients taking mainly second-generation antidepressants. Because of the good tolerability of the latter and the flat dose-response relationship, genotyping should only be considered in cases of suspected side effects.

Standardized rater training for the Hamilton Depression Rating Scale (HAMD-17) in psychiatric novices.

BACKGROUND: Despite the long and widespread use of the Hamilton Depression Rating Scale (HAMD), standardized reliability studies in inexperienced raters are not available. METHODS: Rater training was carried using three videotaped interviews with depressed patients in 21 psychiatric novices who had negligible previous experience with the HAMD. Chance-corrected coefficients of rating agreement with expert standards (weighted kappa, ICC) were computed for single items and the total score of the HAMD. RESULTS: The results demonstrate sufficiently high interrater reliability (kappa>0.60) for most of the HAMD items and the total score (ICC=0.57-0.73). Three standardized HAMD training sessions seem adequate to establish satisfactory agreement among psychiatric novices. LIMITATIONS: The sample of video-taped interviews and, hence, the generalizability of the results, was restricted. CONCLUSIONS: High inter-rater reliability of the HAMD justifies the use by clinically inexperienced researchers after standardized training.