Efficacy and tolerability of lamotrigine in Juvenile Myoclonic Epilepsy in adults: A prospective,unblinded randomized controlled trial

PurposeControlled randomized studies recommending the clinical use of lamotrigine in adult populations with the diagnosis of Juvenile Myoclonic Epilepsy are still lacking. To compare the efficacy and tolerability of lamotrigine versus valproate in adult patients with JME.MethodsThis was a prospective, randomized, controlled, pragmatic, long-term and open-label treatment trial. Patients were randomized to use valproate or lamotrigine. The primary end points of the study were: (1) time from randomization to treatment failure (withdrawal); (2) time from randomization to seizures remission. Secondary ending points were: (1) frequency of clinically important adverse events and (2) change in the QOLIE-31 after randomization. The definition of seizure remission was based on disappearance of all seizure types and EEG discharges.ResultsWe found that the time to withdraw treatment after randomization was not significantly different in lamotrigine and valproate groups. Long-term seizures freedom was equal in the both groups of the trial; only 8 (19.1%) patients randomized to lamotrigine and 6 (19.4%) randomized to valproate were not seizure free after 4 months of treatment. Between 17.03% (lamotrigine) and 35.3% (valproate) of patients reported adverse reactions at some point in the intention-to treat study (p = 0.07). All subscales of the QOLIE-31 questionnaire, except that related to side effects of medication, improved more than 5 points with respect to baseline period in both groupsConclusionLamotrigine is effective in adult patients with Juvenile Myoclonic Epilepsy and better tolerated than valproate, although the incidence of idiosyncratic reactions could be a cause of concern.     

Thrombophilia and Hypercoagulation: Risk Assessment and Screening

The case of a patient who originally had a laparoscopic cholecystectomy and subsequently suffered a massive thromboembolic event is presented to highlight the importance of identifying risk factors for and screening of patients with acquired and/or inherited thrombophilic defects. While the prevalence of these hypercoagulable conditions is low, failure to recognize the risks for and consequences of these states can have fatal results. This article presents the case study followed by a review of the current recommendations for the screening of hypercoagulable risks/states and how those results should or should not impact the management of patients with venous thrombotic events     

Knowledge and Perspectives of Breast and Cervical Cancer Screening Among Female African Immigrants in the Washington D.C. Metropolitan Area

Black women in the USA have both a higher percentage of late-stage diagnoses as well as the highest rates of mortality from breast cancer when compared to women of other ethnic subgroups. Additionally, Black women have the second highest prevalence of cervical cancer. Many reports evaluating the cancer outcomes of Black women combine data on African-born immigrants and US-born Blacks. This categorization ignores subtle yet important cultural differences between the two groups, which may ultimately affect breast and cervical cancer screening practices. Therefore, this study investigated knowledge and awareness levels of breast and cervical cancer screening practices among female African-born immigrants to the USA residing in the Washington D.C. metropolitan area. Data were collected from 38 participants through key informant interviews, focus group sessions, and a sociodemographic questionnaire over a 3-month study period. Results suggest that fatalism, stigma, and privacy are among the major factors that affect the decision to seek preventative screening measures for breast and cervical cancer among this population. Additionally, the study implies that cervical cancer awareness is significantly lower among this population when compared to breast cancer. This study highlights differences between women of African descent residing in the USA and the need for continued research to increase understanding of the manner in which immigrant status affects health-seeking behavior. This information is critical for researchers, physicians, and public health educators aiming to design culturally appropriate interventions to effectively reduce the prevalence of breast and cervical cancer among female African immigrants living in the USA.     

A Comparison of the Effects of Oral Glutamine Dipeptide,Glutamine, and Alanine on Blood Amino Acid Availability in Rats Submitted to Insulin-Induced Hypoglycemia

We compared the effects of oral administration of high-dose or low-dose glutamine dipeptide (GDP), alanine (ALA), glutamine (GLN), and ALA + GLN on the blood availability of amino acids in rats submitted to insulin-induced hypoglycemia (IIH). Insulin detemir (1 U/kg) was intraperitoneally injected to produce IIH; this was followed by oral administration of GDP, GLN + ALA, GLN, or ALA. We observed higher blood levels of GLN, 30 min after oral administration of high-dose GDP (1000 mg/kg) than after administration of ALA (381 mg/kg) + GLN (619 mg/kg), GLN (619 mg/kg), or ALA (381 mg/kg). However, we did not observe the same differences after oral administration of low-dose GDP (100 mg/kg) compared with ALA (38.1 mg/kg) + GLN (61.9 mg/kg), GLN (61.9 mg/kg), or ALA (38.1 mg/kg). We also observed less liver catabolism of GDP compared to ALA and GLN. In conclusion, high-dose GDP promoted higher blood levels of GLN than oral ALA + GLN, GLN, or ALA. Moreover, the lower levels of liver catabolism of GDP, compared to ALA or GLN, contributed to the superior performance of high-dose GDP in terms of blood availability of GLN.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).