Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

BACKGROUND: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. RESULTS: 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch-related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. CONCLUSION: This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment.

Modelagem comparativa da cinética da fase sólida do capim-elefante picado, suplementado ou não com concentrados, e fornecido a vacas Holandês x Zebu em lactação / Comparative modeling of chopped elephantgrass particulate kinectics in crossbred lactating cows receiving or not concentrate supplement

Foram comparadas as estimativas da cinética da fase sólida do capim-elefante (Pennisetum purpureum, Schum.) picado, mordentado com cromo (Cr), obtidas do ajuste de dois modelos não-lineares (bicompartimental tempo-independente e multicompartimental tempo-dependente) a resultados de excreção fecal de vacas Holandês x Zebu em lactação. Utilizaram-se dados de dois experimentos realizados em anos diferentes com capim-elefante cortado aos 60 e 45 dias, e suplementado, 3,3kg/vaca/dia, base matéria natural, ou não com concentrados. Foram utilizadas quatro e três vacas, respectivamente, no primeiro e no segundo ano de experimentação, havendo sempre duas fases de coleta de dados, necessárias para permitir que cada vaca pudesse ser avaliada em cada tratamento. As taxas de passagem ruminal estimadas variaram de 3,0 a 3,2 por cento/h no modelo bicompartimental tempo-independente, e de 2,6 a 3,0 por cento/h no modelo multicompartimental tempo-dependente, enquanto as respectivas taxas de passagem pós-ruminal variaram de 4,9 a 7,4 por cento/h e de 7,4 a 10,9 por cento/h. Os tempos médios de retenção do capim-elefante no trato gastrintestinal das vacas variaram de 66,0 a 76,2h no modelo bicompartimental tempo-independente, e de 48,1 a 57,8h no modelo multicompartimental tempo-dependente. O processo de dependência de tempo imposto pelo modelo multicompartimental permitiu melhor ajuste aos dados de excreção fecal do Cr, em relação ao modelo bicompartimental.

Particulate kinetics estimates of chopped elephantgrass (Pennisetum purpureum, Schum.) mordanted with Chromium (Cr) were obtained and compared by the adjustment of two nonlinear models - age-independent double-compartmental model and age-dependent multicompartmental model - to a Cr faecal excretion dates of lactating crossbred Holstein x Zebu cows. Results from two trials carried out in different years with elephantgrass cut at 60 and 45 days of growth and supplemented, 3,3 kg/cow/day, wet basis, or not with concentrates were used. Four cows in the first and three cows in the second year were used and in each year there were two phases of collection of data, necessary to allow that each cow could be evaluated in each treatment. The ruminal particulate passage rates of chopped elephantgrass ranged from 3.0 to 3.2 percent/h in age-independent double-compartmental model, and from 2.6 to 3.0 percent/h in age-dependent-multicompartmental model, while that the respective post-ruminal passage rates ranged from 4.9 to 7.4 percent/h and from 7.4 to 10.9 percent/h. The total mean retention time of the elephantgrass in the gastrointestinal tract ranged from 66.0 to 76.2 h in age-independent double-compartmental model, and from 48.1 to 57.8 h in age-dependent-multicompartmental model. The implicit assumption of age-dependence for the multicompartimental model allowed better fit to the data of faecal excretion Cr than that one of the double-compartmental model.

A comparison of the OPUS and TDx analysers for antiepileptic drug monitoring.

Therapeutic drug monitoring of a variety of antiepileptic drugs is used routinely as a guide to individualising the drug treatment of patients with epilepsy. Thin dry film multilayer immunoassays (OPUS) for carbamazepine, phenytoin, phenobarbitone, and valproic acid were evaluated and compared with fluorescence polarisation immunoassay (TDx), using commercially available control material and patient sera. For the OPUS, the within-batch coefficient of variation (CV) for the different drugs in the control material varied between 3.9% (phenobarbitone) and 8.1% (valproic acid). The between-batch CVs varied between 5.3% (valproic acid) and 18.3% (carbamazepine). The comparative between-batch CVs for the TDx varied between 2.0% (phenytoin) and 7.0% (valproic acid). Analysis of 209 patient samples containing carbamazepine, phenytoin, phenobarbitone, or valproic acid demonstrated significant correlation between the two analytical methods, with correlation coefficients of 0.9336, 0.9560, 0.9448, and 0.9618, with slopes of the regression lines of 0.9042, 0.8663, 1.1368, and 1.1244, respectively. It is concluded that both the TDx and OPUS instruments exhibit comparable performance for the analysis of carbamazepine, phenobarbitone, phenytoin, and valproic acid in patient samples. Moreover, the OPUS instrument, with its facilities of random assay access and statim analysis, may be useful in an outpatient setting in which a major consideration would be a rapid turnaround of patient assay results.

Lamotrigine-induced carbamazepine toxicity: an interaction with carbamazepine-10,11-epoxide.

We report an interaction between lamotrigine (LTG), a new antiepileptic drug (AED), and carbamazepine (CBZ) and its primary metabolite CBZ-10,11-epoxide (CBZ-E) in 9 consecutive patients (5 male, 4 female, aged 19-31 years). After introduction of LTG (median daily dose 200 mg, range 100-300 mg) the mean serum CBZ-E concentration increased by 45% (P less than 0.01) and the CBZ-E/CBZ ratio increased by 19% (P less than 0.02). In 4 patients these changes were associated with clinical toxicity (dizziness, nausea, diplopia). The possibility of an increase in serum CBZ-E concentrations needs to be considered if toxicity symptoms develop when LTG is added to CBZ therapy.

Protein binding of oxcarbazepine and its primary active metabolite, 10-hydroxycarbazepine, in patients with trigeminal neuralgia.

Oxcarbazepine, a new drug with antineuralgic properties has been evaluated in a long-term follow-up of 6 patients (2 males, 4 females; aged 42-77 years; mean 61 years), previously reported on with trigeminal neuralgia. Daily oral oxcarbazepine dose correlated significantly with both total oxcarbazepine (r = 0.851) and 10-OH-carbazepine (r = 0.958) serum concentrations. Mean percent free oxcarbazepine and 10-OH-carbazepine was 41 and 61% respectively and there was no significant difference in binding between male and female patients. Free serum concentrations of oxcarbazepine and 10-OH-carbazepine correlated significantly with total serum oxcarbazepine and 10-OH-carbazepine respectively, indicating that binding capacity of both are essentially constant within the respective ranges of 0.2-11.4 mumol.l-1 and 20-150 mumol.l-1 observed in the present study.

Dose dependent enzyme induction by oxcarbazepine?

Antipyrine half life and clearance was compared in four patients with classical idiopathic trigeminal neuralgia during carbamazepine (CBZ) or CBZ/phenytoin (PHT) and after substitution with oxcarbazepine (OXC) monotherapy. OXC is observed to be less of a hepatic enzyme inducer than CBZ or CBZ/PHT in combination, however induction by OXC may be dose related.

Carbamazepine and carbamazepine-10,11-epoxide pharmacokinetics in an overdose patient.

A case report on a 13-year-old girl with idiopathic grand mal epilepsy who ingested 34 g carbamazepine (CBZ) and 80 mg clonazepam is presented. The patient survived but suffered severe temporary neurological toxicity characteristic of CBZ. CBZ was 79.6 +/- 2.8% bound to serum protein and carbamazepine-10,11-epoxide (CBZ-E) binding was essentially concentration dependent. CBZ and CBZ-E elimination half-lives were 26 and 16.5 h respectively. An inhibitory metabolic interaction with the co-ingested clonazepam is suggested.

Total and free serum concentrations of carbamazepine and carbamazepine-10,11-epoxide in children with epilepsy.

Simultaneous steady-state serum total and free (non-protein-bound) concentrations of carbamazepine and carbamazepine-10,11-epoxide were measured in 68 patients under the age of 21 years with epilepsy (44 males, 24 females; mean age, 11.8 +/- 4.5 years). Thirty patients were maintained on monotherapy with carbamazepine. Mean serum total carbamazepine and carbamazepine-10,11-epoxide concentrations obtained were 7.0 +/- 2.4 mg/L (29.5 +/- 10.0 mumol/L) and 1.5 +/- 0.6 mg/L (5.9 +/- 2.6 mumol/L), respectively. Mean serum-free carbamazepine and carbamazepine-10,11-epoxide concentrations obtained were 1.3 +/- 0.5 mg/L (5.7 +/- 2.1 mumol/L) and 0.5 +/- 0.3 mg/L (2.2 +/- 1.1 mumol/L), respectively. Binding of carbamazepine and carbamazepine-10,11-epoxide was 81% +/- 3% and 62% +/- 10%, respectively. There was no significant difference in binding between male and female patients or those maintained on monotherapy and polytherapy. Age correlated significantly with carbamazepine binding but not with carbamazepine-10,11-epoxide binding. Free concentrations of carbamazepine and carbamazepine-10,11-epoxide correlated significantly with total carbamazepine and total carbamazepine-10,11-epoxide concentrations, respectively, indicating that the binding capacities of both carbamazepine and carbamazepine-10,11-epoxide are constant at serum total carbamazepine concentrations within the quoted therapeutic range.

Factors influencing simultaneous concentrations of total and free carbamazepine and carbamazepine-10, 11-epoxide in serum of children with epilepsy.

Various factors that may influence the simultaneous concentration of total and free carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) in serum of 68 children (mean age 11.8 +/- 4.5 years) with epilepsy were assessed. Separation of free and bound drug fractions was achieved by ultrafiltration, and CBZ and CBZ-E concentrations were determined using a sensitive high pressure liquid chromatographic technique. Thirty children were on CBZ monotherapy. Both total CBZ and CBZ-E serum concentrations correlated significantly with their respective free serum concentrations. CBZ was 81 +/- 3% and CBZ-E 63 +/- 9% bound. There was no correlation between the CBZ dose and either CBZ total or free serum concentrations. A statistically significant correlation was, however, observed between CBZ dose and simultaneous CBZ-E total and free concentrations. CBZ total and free concentrations correlated significantly with those of total CBZ-E. A significant negative correlation was observed between age and total (r = -0.49, p less than 0.01) and free (r = -0.43, p less than 0.025) CBZ-E/CBZ ratios. Concomitant drug therapy (phenytoin, phenobarbitone, and sodium valproate) significantly elevated CBZ-E/CBZ ratios.

The interaction of denzimol (a new anticonvulsant) with carbamazepine and phenytoin.

Denzimol, a new anticonvulsant drug, is currently undergoing clinical evaluation. In this paper we report its use in six patients who were also taking carbamazepine and two patients taking phenytoin. There was a striking elevation of serum carbamazepine, carbamazepine-10, 11 epoxide and phenytoin concentrations in all patients on the addition of denzimol therapy. The interaction with carbamazepine is greater in severity than any other reported to date and denzimol's interaction with both carbamazepine and phenytoin is likely to prove of major clinical significance.

Altered ratio of carbamazepine-10,11-epoxide/carbamazepine in plasma of children: evidence of anticonvulsant drug interaction.

A method of measuring carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) has been developed and used to monitor plasma concentrations in children suffering from various forms of epilepsy. Children stabilised on standard doses of CBZ alone showed a ratio of CBZ-10,11-EPOX/CBZ of 18.92 +/- 8.08, expressed as a percentage of the CBZ concentration, while those on multiple-drug therapy (with the exception of benzodiazepines and phenobarbitone) showed both increased values of CBZ-10,11-EPOX/CBZ ratio and increased absolute concentrations of CBZ-10,11-EPOX in plasma. These changes correlated with clinical side-effects which could not be attributed to CBZ itself or to the other drugs administered concurrently.

Correlation between plasma carbamazepine-10,11-epoxide concentration and drug side-effects in children with epilepsy.

Ninety children with epilepsy were treated with carbamazepine (CBZ) alone or with other anticonvulsant drugs. Side-effects were noted in 14 patients. When 25 patients treated with CBZ alone (group 1) were compared with 27 on CBZ and sodium valproate (group 2) and with 38 on CBZ and one or more other anticonvulsants (group 3), the incidence of side-effects was two in group 1 (of whom one patient had a toxic plasma level of CBZ), but 12 in groups 2 and 3 combined. In all but three of the 14 patients with side-effects, plasma levels of CBZ were within the 'therapeutic range'. A significant difference was found between the carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) levels in plasma and CBZ-10,11-EPOX/CBZ ratio in patients with and without side-effects. For five patients on CBZ and other drugs, changes in treatment resulted in changes in side-effects, and also in CBZ-10,11-EPOX levels. Three of these patients showed an interaction between CBZ and sodium valproate, with a correlation between plasma CBZ-10,11-EPOX and side-effects when either drug was introduced or withdrawn, the plasma levels of CBZ itself and of sodium valproate being within the 'therapeutic range'.

Routine monitoring of carbamazepine and carbamazepine-10,11-epoxide in plasma by high-performance liquid chromatography using 10-methoxycarbamazepine as internal standard.

Carbamazepine and carbamazepine-10,11-epoxide were separated by high-performance liquid chromatography (HPLC) with acetonitrile-water as mobile phase, and detection was effected by UV absorption at 215 nm with a total retention time of less than 10 min. Plasma samples were extracted with dichloromethane and 4 M sodium hydroxide, and 10-methoxy-carbamazepine was added as internal standard. Other commonly used anticonvulsant drugs present in plasma showed no significant interference. The within-batch coefficient of variation for carbamazepine was 4.9% and carbamazepine-10,11-epoxide 5.9%. Between-batch coefficients of variation were 3.7% and 5.3%, respectively. Mean recovery for carbamazepine was 100.2% and for carbamazepine-10,11-epoxide 100.6%. This HPLC method was compared with both an enzyme immunoassay procedure (EMIT) and a gas-liquid chromatographic (GLC) method. Correlation coefficient between HPLC/EMIT for carbamazepine was 0.983, HPLC/GLC carbamazepine 0.988 and HPLC/GLC carbamazepine-10,11-epoxide 0.981.

Valproic acid estimation by enzyme immunoassay.

Blood samples from patients on long-term sodium valproate (Epilim) therapy were analysed for valproic acid by two procedures, enzyme immunoassay (EMIT) and gas-liquid chromatography (GLC). A critical evaluation of the effects of anticoagulants added to specimens was performed in addition to studies on reagent specificity, accuracy, and precision. EMIT valproic acid reagent showed high specificity, and there was a good correlation between results obtained by EMIT and GLC over a wide range of concentrations. The accuracy and precision of EMIT assay was good over the therapeutic range of valproic acid. The presence of the anticoagulant EDTA or of fluoride/oxalate produced a bias towards high results for valproic acid as compared with those obtained from the analysis of serum.