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Aims: The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing and there are limited data on response to PAH‐targeted therapies in this population. These post hoc analyses explored the effect of selexipag in PAH patients with cardiovascular comorbidities in the GRIPHON study. Methods and results: Randomized patients (n = 1156) were classified using three methods: (i) by subgroups defined according to previously published comorbidity count and restrictive haemodynamic criteria: Subgroup A (<3 comorbidities and haemodynamic criteria met; n = 962) and Subgroup B (≥3 comorbidities and/or haemodynamic criteria not met; n = 144); comorbidities included body mass index ≥30 kg/m2, essential hypertension, diabetes, history of coronary artery disease; (ii) by number of comorbidities, with addition of atrial fibrillation (0, 1, 2, 3, 4, or 5); (iii) by presence of individual comorbidities. Selexipag to placebo hazard ratios (HR) and 95% confidence intervals (CI) for morbidity/mortality (primary composite endpoint) were estimated using Cox regression adjusting selexipag effect for baseline covariates. Approximately half of the patients in GRIPHON (n = 584; 50.5%) had comorbidities. Selexipag reduced the risk of a morbidity/mortality event compared with placebo in both Subgroup A (HR 0.66, 95% CI 0.53, 0.82) and Subgroup B (HR 0.50, 95% CI 0.26, 0.96), with no evidence of an inconsistent treatment effect between subgroups (interaction p = 0.432). Consistent results were observed in analyses by number and by specific type of comorbidity. Conclusion: Selexipag reduces the risk of a morbidity/mortality event vs. placebo irrespective of patient comorbidity status, suggesting that comorbidity status does not influence the treatment effect of selexipag. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference).Methods: In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400 mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6 h. Time between dosing and the start of absorption (Tlag); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (Cmax) of the reference (standard ibuprofen acid) (TCmaxRef); and time to achieve therapeutic plasma concentration were measured.Results: Ibuprofen was absorbed more rapidly from the salt formulations than the reference; Tlag was 3.3-6.4 min for salt formulations compared with 10.9 min for the reference, and 100% of subjects had a Tlag ≤ 5 min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. TCmaxRef was 3.22-5.74-times shorter for salt formulations than for the reference (all p < .0001). The salt formulations reached therapeutic levels earlier than the reference (all p < .0001). All formulations were well tolerated.Conclusions: This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. Tlag and TCmaxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia. [ABSTRACT FROM AUTHOR]

Abstract: Traditionally, allergic contact dermatitis (ACD) has been associated with the activity of Th I lymphocytes that secrete interferon gamma. Recent evidence indicates that other cells, e.g. interleukin 5 (lL-5)-secreting Th2 or Tc2 cells may be among the key effectors of ACD. The aim of the present study was to assess the influence of nickel-specific IFN-gamma secretion (marker of Thl and Tel activity) and IL-S secretion (Th2 and Tc2) on the clinical outcome (patch test score) in nickel-allergic patients. 40 women with suspicion ofACD were involved, aged from 14-54 (median 31.5) years. They were patch tested with NISO4. Peripheral blood mononuclear cells (PBMC) from the patients were cultured and analysed for IFN-gamma and IL-S secretion in response to NiSO4. A series of statistical models (classical logit or cloglog link function) were used. We demonstrate that nickel-specific IL-S secretion by PBMC is correlated with the intensity of patch test reaction (p=0.05), with no significant effect of IFN-gamma. An increase in the nickelspecific IL-S secretion from PBMC by 10 pg/mI is associated with a 10-20% increase (depending on statistical model) in the odds ratio of the patient to have a higher patch test score. These findings support the assumption that cells secreting IL-S (e.g. Th2, Tc2) play a more important role in the pathogenesis ofACD than previously thought. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference).Methods: In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400 mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6 h. Time between dosing and the start of absorption (Tlag); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (Cmax) of the reference (standard ibuprofen acid) (TCmaxRef); and time to achieve therapeutic plasma concentration were measured.Results: Ibuprofen was absorbed more rapidly from the salt formulations than the reference; Tlag was 3.3-6.4 min for salt formulations compared with 10.9 min for the reference, and 100% of subjects had a Tlag ≤ 5 min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. TCmaxRef was 3.22-5.74-times shorter for salt formulations than for the reference (all p < .0001). The salt formulations reached therapeutic levels earlier than the reference (all p < .0001). All formulations were well tolerated.Conclusions: This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. Tlag and TCmaxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the dynamics of serum levels of tranaminases (ALT and AST) as well as the levels of alkaline phosphate and gammaglutamylotranspeptydase in the course of the disease in two groups of patients with a mild form of acute biliary pancreatitis (ABP). The first group included 54 patients with "rescued" gall bladders (group -- Ch), and the second one was composed of 15 patients who had previously undergone a cholecystectomy (post cholecystectomy group -- P). Both groups underwent the same model of treatment with ERCP followed by an endoscopic sphincterotomy on the first day of hospitalization. We are aware that the question of the indication for these procedures, in patients with mild forms of acute biliary pancreatitis, is still debatable. The level of measured parameters were insignificantly different. In these enzymes the same dynamics regarding time (decrease in time) were noticed in both groups. There were no differences in the duration of hospitalization between the groups. We discovered that the level of alkaline phosphate could be a factor influencing the risk of once patients are discharged from hospital (Cox's regression model). We believe that an early endoscopic sphincterotomy should be performed on every patient who has previously undergone a cholecystectomy. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference)., Methods: In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400 mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6 h. Time between dosing and the start of absorption (T lag ); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (C max ) of the reference (standard ibuprofen acid) (T C maxRef ); and time to achieve therapeutic plasma concentration were measured., Results: Ibuprofen was absorbed more rapidly from the salt formulations than the reference; T lag was 3.3-6.4 min for salt formulations compared with 10.9 min for the reference, and 100% of subjects had a T lag ≤ 5 min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. T C maxRef was 3.22-5.74-times shorter for salt formulations than for the reference (all p < .0001). The salt formulations reached therapeutic levels earlier than the reference (all p < .0001). All formulations were well tolerated., Conclusions: This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. T lag and T C maxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia.

Traditionally, allergic contact dermatitis (ACD) has been associated with the activity of Th1 lymphocytes that secrete interferon gamma. Recent evidence indicates that other cells, e.g. interleukin 5 (IL-5)-secreting Th2 or Tc2 cells may be among the key effectors of ACD. The aim of the present study was to assess the influence of nickel-specific IFN-gamma secretion (marker of Th1 and Tc1 activity) and IL-5 secretion (Th2 and Tc2) on the clinical outcome (patch test score) in nickel-allergic patients. 40 women with suspicion of ACD were involved, aged from 14-54 (median 31.5) years. They were patch tested with NiSO(4). Peripheral blood mononuclear cells (PBMC) from the patients were cultured and analysed for IFN-gamma and IL-5 secretion in response to NiSO(4). A series of statistical models (classical logit or cloglog link function) were used. We demonstrate that nickel-specific IL-5 secretion by PBMC is correlated with the intensity of patch test reaction (p=0.05), with no significant effect of IFN-gamma. An increase in the nickel-specific IL-5 secretion from PBMC by 10 pg/ml is associated with a 10-20% increase (depending on statistical model) in the odds ratio of the patient to have a higher patch test score. These findings support the assumption that cells secreting IL-5 (e.g. Th2, Tc2) play a more important role in the pathogenesis of ACD than previously thought.

Unlabelled: The aim of this paper is epidemiological analysis of poisonings with amphetamine and tetrahydrocanabinols (THC), particularly in three aspects: (1) co-occurrence of other substances (mixed poisonings); (2) factors shaping dynamics in number of poisonings and 3) average age of patients. The data this paper is based on come from the data set "Duch" which is run by the Department of Analytical Toxicology and Drug Monitoring UJ CM in Kraków. The data were collected between 1 Dec. 2001 and 28 Feb. 2005 (1186 days). Amphetamine and THC were determined in patient's urine in semi-quantitative manner by means of EMIT and FPIA methods., Results: Amphetamine: In the studied period amphetamine was confirmed in 493 patients. Other substances were confirmed in 57.6% of patients: opiates--28.6% THC--14.2%, opiates and THC--5.9%. Since the beginning of the studied period till mid Aug 2003 daily number of cases showed increasing trend (0.062% per day), then the tendency was reversed (-0.074% per day). We observed more males than females (3.24:1). Most cases were poisoned on Mondays, less during the week and least on weekends. At the beginning of the studied period males were older than females (27 vs. 20 years). As the time progressed average age of males was stable but in women average age was increasing at the rate 0.004 year per day. As a consequence of this trend in winter 2004/2005 average age of both sexes was equal. THC: We observed 410 cases with confirmed presence of THC in urine. Other substances were confirmed in 40.2% of patients: amphetamine 17.1% amphetamine and opiates 7.1, opiates 7.1%. There were 17 various substances accompanying THC. In our material the sex ratio was biased toward males (7.8 to 1). Weekly dynamics of poisonings with THC have the same pattern as the one observed in amphetamine. At the beginning of the studied period males were older than females (28 vs. 20 years). Changes in averages followed the same pattern as in amphetamine.

Background: Carbamazepine (CBZ) is an antiepileptic drug with tricyclic structure which implies its potential cardinotxic properties, especially in acute poisoning., Aim: To evaluate some cardiovascular effects connected with CBZtoxicity and tofind the relation between them and CBZ plasma level., Material and Methods: 34 patients (18 males, 16 females; median age 24.5) hospitalized in our Department in 1996-1997 and 2005-2006 due to acute CBZ poisoning. Analysis included following parameters: systolic (SBP) and diastolic (DBP) blood pressure, ECG parameters: heart rate (HR), duration of QRS complex, PQ interval and corrected QT interval (QTc) calculated with Bazett's (QTc(B)) and Hodges's (QTc(H)) formulas. These parameters were compared with reference values for general population available in the literature. Relations between above mentioned parameters and CBZ plasma level were studied by means of Generalized Additive Model (GAM)., Results: The reference values were exceeded most often for QRS (62%), DBP and QTc(B) (53%, both) and SBP (50%). The mean number of parameters with exceeded norms was 3.1 per patient (SD = 1.71). We failed to find any significant correlation between CBZ plasma level and any of the studied parameters. Positive correlation between SBP and DBP (r = 0.68; p < 0.001) and negative correlation between QRS and HR (r = -0.50; p = 0.003) were found., Conclusion: CBZ could affect different cardiovascular parameters which should be monitored in cases of acute drug poisonings.

This paper presents the analysis of trends in a number of cases and an average age of patients for whom determination of tricyclic antidepressants (TCA) showed positive results. The studied data were gathered in toxicological laboratory of Dept. of Analytical Toxicology and Therapeutic Drug, CM UJ in Kraków. The data were collected in period December 2001 August 2004. The main findings of this study are: The number of cases is exponentially increasing at the rate of 0.068% per day (p = 0.0165). No statistically significant correlation between the number of cases and: (a) day-length (p = 0.9819), (b) day-length change (p = 0.2312), (c) direction of change of day-length (p = 0.4640), d) day of the week (p = 0.7588) has been found, so periodicity of this phenomenon is questionable. It has been observed that the average age of patients is decreasing and the estimated rate of this decrease equals 0.0092-years per day (p = 0.0555). TCA positive patients treated in the Clinic on different days of the week differ in average age (p = 0.0016). From Tuesday till Friday the average age of patients is increasing. In the middle of the studied period the increase started from 30-year-olds on Mondays and ended with 48-year-old patients on Friday. At weekends the average dropped to 38 and stayed constant. On Mondays the average was about 46.

There were 10 acutely CO poisoned study patients without CNS history (head traumas, epilepsy, dementia, migraine or alcoholic diseases) in whom (99m)Tc-HmPAO SPET, HMRS and neuropsychological testing were performed. 99mTc-HmPAO SPET and neuropsychological testing were performed twice: in acute phase and at six months post CO exposure. HMRS was carried out at 8 months post CO exposure. A multidimensional analysis of variance (MANOVA) was used to statistical analysis. Regional CBF disturbances in acute phase of CO poisoning were observed in frontal cortex, basal ganglia and parietal cortex respectively. The most reversible, as seen in control (99m)Tc-HmPAO SPET examination, were the changes observed in parietal cortex. Diffuse generalized cortex hypoperfusion, both in acute phase and at 6 months post exposure, was seen only in one the patient. In all of the examined patients different elevation in mobile lipid or/and lactate concentration in frontal lobe or/and basal ganglia was revealed by HMRS evaluation at eight months post acute CO exposure. Results of neuropsychological testing at baseline and at 6 months partially correlated with neuro-imagine techniques applied.

Carbamazepine is an antiepileptic drug widely used by neurological and psychiatric patients. Because of it's low therapeutic index and increasing number of acute carbamazepine intoxications there is a need of routine serum carbamazepine assay in toxicological laboratories. Determinations of serum carbamazepine concentrations are 5.3% of all toxicological analysis carried on in Department of Analytical Toxicology and Therapeutic Drug Monitoring, Collegium Medicum, Jagiellonian University in Kraków. The goal of the study was comparison of two analysis methods: FPIA and HPLC-DAD for the diagnostics of patients intoxicated with carbamazepine. Material for analysis were 21 samples of blood collected from poisoned patients treated in Department of Clinical Toxicology in Kraków. Measurements of serum carbamazepine concentration by FPIA method and carbamazepine and it's main active metabolite carbamazepine-10,11-epoxide concentrations by HPLC-DAD method were made. Statistical analysis showed that serum carbamazepine concentrations measured by FPIA method were higher than serum carbamazepine concentrations measured by HPLC-DAD method (t21 = 2.21, p = 0.0384). The mean difference of serum carbamazepine concentrations measured by the two methods was 2.67 mg/l (SD = 5.69 mg/l) and didn't depend on the carbamazepine concentration measured by FPIA method (r = -0.137, p = 0.5431). There was no statistical difference between serum carbamazepine concentration measured by FPIA method and the sum of serum carbamazepine and carbamazepine-10,11-epoxide concentrations measured by HPLC-DAD method (t21 = 1.42, p = 0.1690).

Social competence were analysed using the origin Polish Questionnaire of Social Competence questionnaire (KKS). The competence gained during the life span are dependent on age, temperament, personality and partially on intelligence. There were 66 drug users (22 females, and 44 males) from methadone maintenance treatment programme conducted in Rydygier's Hospital. Social Exposure Scale, Scale of Assertiveness, Scale of Direct Interpersonal Contacts separately as well as the sum of information were used for estimation of the competence. The patient age at narcotic initiation, duration of being in methadone substitution programme, means of support were a statistically significant factors. A significant differences between two group as regard the psychopathology the drug abuse alone or coincidence with psychiatric diagnosis were also noted.

Name-day party is a feature of the Polish culture. During these parties alcoholic drinks are served very often. In this paper it is shown that there is a positive correlation between the popularity of a name-day and the number of ethanol poisonings. Another finding of this paper is that the popularity of a name-day is also associated with the average age of ethanol-poisoned patients. This association is mediated by gender and a day of the week. On days of popular names the average age of poisoned woman is lower comparing to days of unpopular names. In case of males the pattern is more complicated. If a name-day of common names occurs on a week day then the male patients tend to be older, but if such a day occurs at the weekend then average age of male patients is higher.