Atrial fibrillation in patients with heart failure

Atrial fibrillation and heart failure are very common cardiac disorders, and both are associated with symptoms, significant morbidity, and mortality. Studies have attempted to determine the prognostic significance of atrial fibrillation in patients with heart failure. Whether atrial fibrillation is an independent risk factor of mortality remains controversial. Multiple trials using either pharmacologic or nonpharmacologic therapies in an attempt to manage atrial fibrillation have been developed. The purposes of this review are to present an overview of atrial fibrillation in patients with heart failure and to discuss the prevalence, prognostic significance, complications, mechanisms, and trials that have formed the therapies presently used.     

Dynamic external fixation for pilon fractures of the interphalangeal joints

Eight consecutive pilon fractures of the finger proximal interphalangeal joint and one of the interphalangeal joint of the thumb were treated by closed reduction and application of a new dynamic external fixator. The average range of movement achieved was 12 degrees -88 degrees and there were no serious complications. The technique described offers an effective and simple solution for treatment of pilon fractures of the interphalangeal joint.     

Obstructive sleep apnea is associated with alterations in markers of fetoplacental wellbeing

Background: Obstructive sleep apnea (OSA) has been associated with adverse fetal outcomes in some studies. Second trimester Down syndrome screening markers reflect fetal and fetoplacental wellbeing. We aimed to compare markers of fetal and feto-placental wellbeing in women with OSA and low risk controls.

Methods: A retrospective case-control study of pregnant women with OSA and available second trimester markers was performed. Controls were screened for sleep disordered breathing (SDB) at the time of delivery using a questionnaire. Women at low risk for OSA were selected. Marker levels were adjusted for gestational age and race and reported as multiples of median and later adjusted for body mass index (BMI).

Results: Twenty-four OSA cases and 166 controls were identified. Women with OSA had a higher mean BMI when compared to controls (37.1?±?12.7 versus 24.1?±?5.1, p?=?0.03). Estriol (uE3) multiples of the median (MoM) levels were lower in women with OSA compared to controls, even after adjusting for BMI, 0.74 (interquartile range (IQR) 0.45) versus 1.06 (IQR 0.38), respectively, p?=?0.026. Once adjusted for BMI, alpha feto-protein (AFP) MoM levels were no longer significantly different in women with OSA compared to controls.

Conclusion: OSA is associated with reduced serum uE3 levels, independently of BMI, possibly indicating fetal distress.     

Evaluation of the likelihood of a selective CHK1 inhibitor (LY2603618) to inhibit CYP2D6 with desipramine as a probe substrate in cancer patients

LY2603618 is a selective inhibitor of deoxyribonucleic acid damage checkpoint kinase 1 (CHK1) and has been in development for the enhancement of chemotherapeutic agents. The study described was to assess the potential interaction between LY2603618 and cytochrome P450 isoform 2D6 (CYP2D6) substrate desipramine in patients with cancer. Before clinical investigation, in silico simulations (using Simcyp®) were conducted. An open‐label, two‐period, fixed‐sequence study was planned in 30 patients with advanced or metastatic cancers, in which a 50 mg oral dose of desipramine was administered alone and in combination with 275 mg of LY2603618 (i.v. infusion). An interim analysis was planned after 15 patients completed both periods. Ratios of geometric least squares means (LSMs) of primary pharmacokinetic (PK) parameters and 90% repeated confidence intervals (RCIs) between desipramine plus LY2603618 and desipramine alone were calculated. Lack of an interaction was declared if the 90% RCI fell between 0.8 and 1.25. The LSM ratios (90% RCI) for areas under the plasma concentration–time curve from time zero to t_last (AUC_[0‐tlast]) and to infinity (AUC_[0‐∞]) and maximum plasma concentration (C_max) were 1.14 (1.04, 1.25), 1.09 (0.99, 1.21) and 1.16 (1.05, 1.29). In silico simulations were predictive of clinical results. Single doses of 275 mg LY2603618 administered with 50 mg desipramine were generally well tolerated. In conclusion, no clinically significant interaction was observed between LY2603618 and desipramine in patients with cancer. In silico predictions of clinical results demonstrated that mechanistic and physiologically based PK approaches may inform clinical study design in cancer patients. Copyright © 2014 John Wiley & Sons, Ltd.     

Interest in multipurpose prevention technologies to prevent HIV/STIs and unintended pregnancy among young women in the United States

Objective

High rates of sexually transmitted infections (STIs) and unintended pregnancy suggest a role for multipurpose prevention technologies (MPTs) designed to combine contraception and infection prophylaxis into one unified method. This study aims to determine factors associated with interest in MPTs among US women.

Multiple-sited (heterotopic) pregnancy after in vitro fertilization and gamete intrafallopian transfer

Pregnancies occurring simultaneously in different body sites (heterotopic pregnancies) are a rare condition thought to occur in 1 of 30,000 spontaneous pregnancies. Individual cases may occur after in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). In the past 4 1/2 years, our unit has performed 6,204 IVF/GIFT or pronuclear stage transfer cycles of treatment. Ten such pregnancies proven by surgical, ultrasound, and histological diagnosis have occurred. In the same period 640 IVF, 355 GIFT, and 6 pronuclear stage transfer clinical pregnancies were achieved. This suggests that the incidence of heterotopic pregnancy after assisted reproduction is closer to 1 of 100 pregnancies. Clinicians managing early complications of IVF, GIFT, and/or pronuclear stage transfer pregnancies should be aware of this relatively high incidence of concomitant intrauterine and extrauterine pregnancy.     

Differentiation of Helicobacter pylori isolates based on lectin binding of cell extracts in an agglutination assay.

Plant and animal lectins with various carbohydrate specificities were used to type 35 Irish clinical isolates of Helicobacter pylori and the type strain NCTC 11637 in a microtiter plate assay. Initially, a panel of eight lectins with the indicated primary specificities were used: Anguilla anguilla (AAA), Lotus tetragonolobus (Lotus A), and Ulex europaeus I (UEA I), specific for alpha-L-fucose; Solanum tuberosum (STA) and Triticum vulgaris (WGA), specific for beta-N-acetylglucosamine; Glycine max (SBA), specific for beta-N-acetylgalactosamine; Erythrina cristagali (ECA), specific for beta-galactose and beta-N-acetylgalactosamine; and Lens culinaris (LCA), specific for alpha-mannose and alpha-glucose. Three of the lectins (SBA, STA, and LCA) were not useful in aiding in strain discrimination. An optimized panel of five lectins (AAA, ECA, Lotus A, UEA I, and WGA) grouped all 36 strains tested into eight lectin reaction patterns. For optimal typing, pretreatment by washing bacteria with a low-pH buffer to allow protein release, followed by proteolytic degradation to eliminate autoagglutination, was used. Lectin types of treated samples were stable and reproducible. No strain proved to be untypeable by this system. Electrophoretic and immunoblotting analyses of lipopolysaccharides (LPSs) indicated that the lectins interact primarily, but not solely, with the O side chain of H. pylori LPS.