Pharmacokinetic/pharmacodynamic considerations for epilepsy – depression comorbidities

Introduction: Epilepsy may be frequently associated with psychiatric disorders and its co-existence with depression usually results in the reduced quality of life of patients with epilepsy. Also, the efficacy of antiepileptic treatment in depressed patients with epilepsy may be significantly reduced.

Areas covered: Results of experimental studies indicate that antidepressants co-administered with antiepileptic drugs may either increase their anticonvulsant activity, remain neutral or decrease the protective action of antiepileptic drugs in models of seizures. Apart from purely pharmacodynamic interactions, pharmacokinetic mechanisms have been proven to contribute to the final outcome. We report on clinical data regarding the pharmacokinetic interactions of enzyme-inducing antiepileptic drugs with various antidepressants, whose plasma concentration may be significantly reduced. On the other hand, antidepressants (especially selective serotonin reuptake inhibitors) may influence the metabolism of antiepileptics, in many cases resulting in the elevation of plasma concentration of antiepileptic drugs.

Expert opinion: The preclinical data may provide valuable clues on how to combine these two groups of drugs – antidepressant drugs neutral or potentiating the anticonvulsant action of antiepileptics are recommended in this regard. Avoidance of antidepressants clearly decreasing the convulsive threshold or decreasing the anticonvulsant efficacy of antiepileptic drugs (f.e. bupropion or mianserin) in patients with epilepsy is recommended.     

Predictors of environmental exposure to polycyclic aromatic hydrocarbons among pregnant women — Prospective cohort study in Poland

Objectives  

The aim of the study was to characterize the PAH exposure level based on 1-hydroxypyrene (1-HP) in urine of Polish pregnant women and to assess the relationship between PAH and factors such as smoking, environmental tobacco smoke exposure, place of residence, heating and cooking method.     

Provision of medical abortion using telemedicine in Brazil

Objective

To evaluate the need for and outcome of self-administered medical abortion with mifepristone and misoprostol in Brazil, provided through Women on Web, a global telemedicine abortion service.

Study Design

A retrospective case review of women from Brazil who contacted Women on Web in 2011. Information from the online consultation, follow-up questionnaire and emails were used to analyze data including demographics, gestational age, outcome of the medical abortion and symptoms that lead to surgical interventions.

Results

The Women on Web website had 109779 unique visitors from Brazil, 2104 women contacted the helpdesk by email. Of the 1401 women who completed the online consultation, 602 women continued their request for a medical abortion. Of the 370 women who used the medicines, 307 women gave follow-up information about the outcome of the medical abortion. Of these, 207 (67.4%) women were 9 weeks or less pregnant, 71 (23.1%) were 10, 11 or 12 weeks pregnant, and 29 (9.5%) women were 13 weeks or more pregnant. There was a significant difference in surgical intervention rates after the medical abortion (19.3% at < 9 weeks, 15.5% at 11–12 weeks and 44.8% at > 13 weeks, p=.06). However, 42.2% of the women who had a surgical intervention had no symptoms of a complication.

Conclusion

There is large need for medical abortion in Brazil. Home use of mifepristone and misoprostol provided through telemedicine is safe and effective. However, after 13 weeks gestation, there is an increased risk of surgical intervention that may be due to the regimen used and local clinical practices in Brazil.

Implications

The current study shows that there is an unmet need for medical abortion in Brazil, a country with legal restrictions on access to safe abortion services. Telemedicine can help fulfill the need and self administration of medical abortion is safe and effective even at late first trimester abortion. Prospective trials are needed to establish safety, effectiveness and acceptability of home use of medical abortion beyond 12 weeks of pregnancy.     

Enhanced Recovery after Surgery (ERAS) Protocol Is a Safe and Effective Approach in Patients with Gastrointestinal Fistulas Undergoing Reconstruction: Results from a Prospective Study

Background and Aims: An enterocutaneous fistula (ECF) poses a major surgical problem. The definitive surgical repair of persistent fistulas remains a surgical challenge with a high rate of re-fistulation and mortality, and the reasons for that is not the surgical technique alone. Enhanced Recovery after Surgery (ERAS^®) is an evidence-based multimodal perioperative protocol proven to reduce postoperative complications. The aim of the study was to assess the clinical value of the ERAS protocol in surgical patients with ECF. Methods: ERAS protocol was used in all patients scheduled for surgery for ECF at the Stanley Dudrick’s Memorial Hospital in Skawina between 2011 and 2020. A multidisciplinary team (MDT) was in charge of the program and performed annual audits. A consecutive series of 100 ECF patients (44 females, 56 males, mean age 54.1 years) were evaluated. Postoperative complications rate, readmission rate, length of hospital stay, prevalence of postoperative nausea and vomiting were assessed. Registered under ClinicalTrials.gov Identifier no. {"type":"clinical-trial","attrs":{"text":"NCT04771832","term_id":"NCT04771832"}}NCT04771832. Results: ERAS protocol was successfully introduced for ECF surgeries; however, eight modifications to the ERAS program was performed in 2015. They led to improvement of surgical outcomes: reduction of postoperative nausea and vomiting (15 vs. 17% patients, p = 0.025), overall complication rate (11 vs. 10, p = 0.021), median length of hospital stay (overall and after surgery, p = 0.022 and 0.002, respectively). Conclusions: ERAS protocol can be successfully used for ECF patients. Prescheduled audits can contribute to the improvement of care.     

Effects of Dietary Oat Beta-Glucans on Colon Apoptosis and Autophagy through TLRs and Dectin-1 Signaling Pathways—Crohn’s Disease Model Study

Background: Crohn’s disease (CD) is characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission. The aim of this study was to determine the time-dependent effects of dietary oat beta-glucans on colon apoptosis and autophagy in the CD rat model. Methods: A total of 150 Sprague–Dawley rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed with feed without beta-glucans (βG−) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. The expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors, in the colon epithelial cells, was determined using immunohistochemistry and Western blot. Results: The results showed that in rats with colitis, after 3 days of induction of inflammation, the expression of Caspase-3 and LC3B in intestinal epithelial cells did not change, while that of TLR 4 and Dectin-1 decreased. Beta-glucan supplementation caused an increase in the expression of TLR 5 and Dectin-1 with no changes in the expression of Caspase-3 and LC3B. After 7 days, a high expression of Caspase-3 was observed in the colitis-induced animals without any changes in the expression of LC3B and TLRs, and simultaneously, a decrease in Dectin-1 expression was observed. The consumption of feed with βGl or βGh resulted in a decrease in Caspase-3 expression and an increase in TLR 5 expression in the CβGl group, with no change in the expression of LC3B and TLR 4. After 21 days, the expression of Caspase-3 and TLRs was not changed by colitis, while that of LC3B and Dectin-1 was decreased. Feed supplementation with βGh resulted in an increase in the expression of both Caspase-3 and LC3B, while the consumption of feed with βGh and βGl increased Dectin-1 expression. However, regardless of the type of nutritional intervention, the expression of TLRs did not change after 21 days. Conclusions: Dietary intake of βGl and βGh significantly reduced colitis by time-dependent modification of autophagy and apoptosis, with βGI exhibiting a stronger effect on apoptosis and βGh on autophagy. The mechanism of this action may be based on the activation of TLRs and Dectin-1 receptor and depends on the period of exacerbation or remission of CD.     

Meta-analysis of prenatal smoking cessation interventions

Our purpose was to assess the effect of prenatal smoking interventions on rates of smoking cessation. A total of 37 trials, conducted between 1976 and 2002 and comprising over 14000 women were identified and included in the meta-analyses. There was a significant increasing in the odds of women who quit smoking in late pregnancy in the intervention group (OR = 1.6; 95% CI 1.4-1.8). The effectiveness of the intervention was significantly higher in the studies that smoking cessation intervention included written materials for pregnant women then in the studies without those materials. The percentage of pregnant women who quit smoking was higher among American women than among women from the European Countries.     

Correlations of alternative medicine,health status and health care in Hungary

INTRODUCTION: Alternative medicine has a growing popularity in Hungary as well as in other Western countries. However, we are in lack of accurate empirical data on the use of this kind of care and its relationship toward official health care system. AIMS: This paper focuses on the questions of the use of, prospective willingness to use, and attitudes toward alternative medicine with regard to the demographic background, general health status and habits of visiting doctors. METHOD: The source of data is a Baranya county health survey from 1999 (N = 2357). The statistical method of analysing data is regression analysis. RESULTS: Alternative medicine is popular mostly in groups of people with younger age, higher level of education and income. Preferring alternative care is connected to having more chronic, non-fatal illnesses while the number of fatal illnesses on one hand and activity restriction on the other have no significant role. Positive relationship to alternative medicine is connected to more overall visits of doctors but less of GP-s. CONCLUSIONS: Regarding the demographic background and health status alternative medicine in Hungary appears similar to what publications from Western countries have already enlighted. Data on utilization of official health care can refer to the possibility that alternative medicine might serve as an alternative of primary care but not of secondary care.     

Niguldipine impairs the protective activity of carbamazepine and phenobarbital in amygdala-kindled seizures in rats.

There is evidence that some calcium (Ca(2+)) channel inhibitors enhance the protective activity of antiepileptic drugs. Since clinical trials have not provided consistent data on this issue, the objective of this study was to evaluate the interaction of a dihydropyridine, niguldipine, with conventional antiepileptics in amygdala-kindled rats. Niguldipine (at 7.5 but not at 5 mg/kg) displayed a significant anticonvulsant effect, as regards seizure and afterdischarge durations in amygdala-kindled convulsions in rats, a model of complex partial seizures. No protective effect was observed when niguldipine (5 mg/kg) was combined with antiepileptics at subeffective doses, i.e. valproate (75 mg/kg), diphenylhydantoin (40 mg/kg), or clonazepam (0.003 mg/kg). Unexpectedly, the combined treatment of niguldipine (5 mg/kg) with carbamazepine (20 mg/kg) or phenobarbital (20 mg/kg) resulted in a proconvulsive action. BAY k-8644 (an L-type Ca(2+) channel activator) did not modify the protective activity of niguldipine (7.5 mg/kg) or the opposite action of this dihydropyridine (5 mg/kg) in combinations with carbamazepine or phenobarbital. A pharmacokinetic interaction is not probable since niguldipine did not affect the free plasma levels of the antiepileptics. These data indicate that the opposite actions of niguldipine alone or combined with carbamazepine (or phenobarbital) were not associated with Ca(2+) channel blockade. The present results may argue against the use of niguldipine as an adjuvant antiepileptic or for cardiovascular reasons in patients with complex partial seizures.