Pattern of adverse events of antiepileptic drugs: results of the aESCAPE study in Poland

Introduction

The Adverse Event Scale in Patients With Epilepsy (aESCAPE) European study ({"type":"clinical-trial","attrs":{"text":"NCT00394927","term_id":"NCT00394927"}}NCT00394927) explored and analyzed adverse events (AEs) and reasons for modifying treatment in patients treated with newer and older antiepileptic drugs (AEDs) used in monotherapy or polytherapy. The present analysis concerns the results of patients recruited in Poland.

Material and methods

Multicentre, international, observational, cross-sectional study investigating AEs in patients with epilepsy (aged ≥ 4 years), on stable AED treatment with one or two AED(s) for ≥ 3 months, using standardized questionnaires completed by a physician during a single study visit.

Results

Out of 309 patients, 24.6% were treated exclusively with newer AED(s) in monotherapy or in combination, while 75.4% were treated with older AED(s) or a combination of older and newer AED(s). 60.8% were on monotherapy, and 39.9% on polytherapy. In general, 73.8% of patients reported ≥ 1 AE(s). There were no significant differences in the frequency of reported AEs in compared groups. The most common were disturbances in cognitive function (40.5%), psychological problems (36.2%), and sedation (32.7%). Some AEs were found to be more specific for particular types and treatment regimens. Changes in treatment or dose during the study visit occurred in 22.3% of the patients, mainly due to lack of efficacy (10.7%), AEs (5.2%) or absence of seizures (4.5%).

Conclusions

A detailed structured interview revealed high frequency of AEs in patients treated with AEDs. The main reasons for treatment modifications at the study visit were lack of efficacy, adverse events and absence of seizures.     

Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

Introduction

The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC).

Material and methods

Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression.

Results

The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1.

Discussion

Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.     

The determinants of chronic bronchitis in Aboriginal children and youth

BACKGROUND:

There is limited knowledge concerning chronic bronchitis (CB) in Canadian Aboriginal peoples.

OBJECTIVE:

To determine the prevalence (crude and adjusted) of CB and its associated risk factors in Canadian Aboriginal children and youth six to 14 years of age.

METHODS:

Data from the cross-sectional Aboriginal Peoples Survey were analyzed in the present study. Logistic regression analysis was used to determine risk factors influencing the prevalence of CB among Aboriginal children and youth. The balanced repeated replication method was used to compute standard errors of regression coefficients to account for clustering inherent in the study design. The outcome of interest was based on the question: “Have you been told by a doctor, nurse or other health professional that you have chronic bronchitis?” Demographics, environment and population characteristics (predisposing and enabling resources) were tested for an association with CB.

RESULTS:

The prevalence of CB was 3.1% for boys and 2.8% for girls. Other significant risk factors of CB were age (OR 1.38 [95% CI 1.24 to 1.52] for 12 to 14 year olds versus six to eight year olds), income (OR 2.28 [95% CI 2.02 to 2.59] for income category <$25,000/year versus ≥$85,000/year), allergies (OR 1.96 [95% CI 1.78 to 2.16] for having allergies versus no allergies), asthma (OR 7.61 [ 95% CI 6.91 to 8.37] for having asthma versus no asthma) and location of residence (rural/urban and geographical location). A significant two-way interaction between sex and body mass index indicated that the relationship between the prevalence of CB and body mass index was modified by sex.

DISCUSSION:

The prevalence of CB was related to well-known risk factors among adults, including older age and lower annual income.     

Salvage radiotherapy in patients with persistently detectable PSA or PSA rising from an undetectable range after radical prostatectomy gives comparable results

Purpose

Salvage radiotherapy (SRT) is applied routinely in patients with a biochemical relapse after radical prostatectomy (RP). Although the detection threshold for relapse after RP has steadily been lowered, only about 30 % of the SRT patients achieve a durable response. We have previously shown the association between a PSA decrease below detectable levels after SRT and biochemical progression-free survival (BPFS). After recalculating our data according to a more recent definition of biochemical failure after SRT, we now show the significance of the post-RP PSA nadir.

Materials and methods

Among 159 prostate cancer patients without hormonal treatment after RP, SRT was given to 72 patients with persistently detectable PSA after RP and to 87 whose PSA increased out of an undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to the prostate bed.

Results

The overall median follow-up time was 41.7 months. The probability for BPFS after this period was 52.8 % in 72 patients with persistently detectable PSA after RP and 65.4 % in 87 patients who had a post-RP PSA nadir below detection limit. Univariate and multivariate analyses showed no significant difference in BPFS of both patient groups (p > 0.05).

Conclusion

Our findings suggest that SRT is a viable treatment option for patients with persistently detectable PSA, giving similar results as in patients whose PSA increases out of an undetectable range after RP.     

Influence of Different Stages of Experimental Chronic Kidney Disease on Rats Locomotor and Postural Skeletal Muscles Microcirculation

Background. Chronic kidney disease (CKD) is associated with muscle excess fatigue and diminished maximal whole body oxygen consumption, which in part could be depended on poor muscle microcirculatory network. The aim of this study was to assume the influence of different stages of CKD on microcirculation vessels in functionally different skeletal muscles—locomotor, the gastrocnemius muscle, and postural, the longissimus thoracis muscle. Methods. Male Wistar rats underwent sham operation (CON), uninephrectomy (CKD 1/2) and subtotal nephrectomy (CKD 5/6). Muscle samples were stained for an alkaline phosphatase to differentiate capillaries. The number of capillaries was estimated by a single observer in 10 μm transverse sections by point counting at a magnification of ×125 using an Image Analysis System Q 500 MC of Leica. Blood pressure and serum creatinine, haptoglobin, MCP-1, VEGF, and PDGF were measured. Results. There were significant differences (p < 0.05) in CD (number of capillaries per 1 mm² of muscle tissue), C:F (capillary to fiber ratio), and CC/F (capillary contact per fiber). The CKD 1/2 group in gastrocnemius and longissimus muscle had 53% and 33% lower C:F; 56% and 33% lower CD; and 44% and 20% less CC/F than CON, respectively. The CKD 5/6 group in gastrocnemius and longissimus muscle had 46% and 20% lower C:F; 47% and 11% lower CD; and 48% and 25% less CC/F versus control, respectively. Blood pressure was higher in CKD 5/6 vs. CKD 1/2 and CON (145/95 vs. 107/87 and 119/77 mmHg, p < 0.05, respectively). CKD 5/6 had higher creatinine than CKD 1/2 and CON (1.22 vs. 0.83 and 0.74 mg/dL, p < 0.05, respectively). Haptoglobin was higher in CKD 1/2 and CKD 5/6 versus CON (1.68 and 1.63 vs. 0.70 mg/mL, p < 0.05, respectively). MCP-1 was higher in CKD 5/6 and CKD 1/2 versus CON (609 and 489 vs. 292 pg/mL, p < 0.05, respectively). There were no significant differences in serum growth factors concentration between groups. Conclusion. Capillary rarefaction is present in early stages of CKD. These changes are independent of blood pressure and progression of CKD. We suspected that muscle function has a big impact on microvasculature as capillaries rarefaction has been reduced more in locomotor than postural skeletal muscle.