Electrocardiographic Diagnosis of Biventricular Pacing in Patients with Nonapical Right Ventricular Leads

Background: Assessment of left ventricular (LV) capture is of paramount importance in patients with biventricular (BiV) pacing. Our goal was to identify electrocardiographic features that differentiate between BiV and right ventricular (RV)‐only pacing in patients with nonapical RV leads. Methods: The study enrolled 300 consecutive patients with BiV devices and nonapical RV leads, and obtained from them 558 electrocardiograms with either BiV pacing (n = 300) or RV‐only pacing (n = 258). RV pacing served as a surrogate for loss of LV capture. Electrocardiograms from the first 150 patients were used to identify BiV‐specific features, and to construct an algorithm to differentiate between BiV and RV‐only pacing. Electrocardiograms from the second 150 patients were used to validate the algorithm. Results: The following electrocardiographic features typical of BiV pacing were identified: QS in lead V6 (specificity = 98.7%, sensitivity = 54.7%), dominant R in lead V1 (specificity = 100%, sensitivity = 23.3%), q in lead V6 (specificity = 96%, sensitivity = 22.7%), and a QRS < 160 ms (specificity = 100%, sensitivity = 66.0%). The algorithm based on those features was found to have an overall diagnostic accuracy of 95.0%, a specificity of 96.0%, and a sensitivity of 93.5%. Conclusions: The study identified QRS features that were very specific for BiV pacing in patients with nonapical RV leads. Sequential arrangement of those features resulted in an algorithm that was very accurate for differentiating between BiV pacing and loss of LV capture. (PACE 2012; 35:1199–1208)     

The ECG Lead I Paradox in Cardiac Resynchronization Therapy

Background: In cardiac resynchronization therapy (CRT), the morphology of the QRS complex plays an important role in the determination of the pacing site and effectiveness of stimulation. Patients and Methods: Review of the electrocardiograms (ECGs) of 737 patients with a CRT device showed a negative QRS complex in lead I during right ventricular (RV) pacing and a positive QRS complex during left ventricular (LV) pacing in four patients. The RV lead was positioned in the high RV septum and the coronary sinus leads in a posterior or postero‐lateral basal level. Reversed ECG lead or pacemaker lead connection, anodal RV stimulation, and scar tissue‐related depolarization abnormalities were excluded as possible causes. Conclusion: Pacing from the high RV septum may rarely lead to a negative QRS complex and basal positions of the LV lead to a positive QRS complex in lead I during LV pacing. The lead I paradox becomes obvious when both phenomena, that are not interrelated, are present in the same patient.     

Alleviation of Pulmonary Hypertension by Cardiac Resynchronization Therapy is Associated with Improvement in Central Sleep Apnea

Background: Recent studies have demonstrated that cardiac resynchronization therapy (CRT) reduces sleep apnea in heart failure (HF); however, the mechanism of benefit remains unclear. Methods: Overnight polysomnography (PSG) was performed in consecutive HF patients who were scheduled for CRT implant. Patients with sleep apnea defined by an apnea‐hypopnea index (AHI) of >10/hour were recruited and underwent echocardiogram examination at baseline and 3 months after CRT. Results: Among 37 HF patients screened, 20 patients (54%) had sleep apnea and 15 of them consented for the study. After 3 months of CRT, there was a significant improvement in New York Heart Association functional class (3.1 ± 0.1 vs 2.1 ± 0.1, P < 0.01), quality‐of‐life (QoL) score (62.9 ± 3.3 vs 56.1 ± 4.5, P = 0.02), left ventricular ejection fraction (LVEF, 28.8 ± 2.5% vs 38.1 ± 2.3%, P < 0.01), and reduction in pulmonary artery systolic pressure (PASP, 41.0 ± 2.7 vs 28.6 ± 2.2 mmHg; P < 0.01) compared with baseline. Repeated PSG after CRT demonstrated a reduction in the duration of arterial oxygen desaturation ≤95% (251.2 ± 36.7 vs 141.0 ± 37.1 minutes), AHI (27.5 ± 4.7 vs 18.1 ± 3.0, P = 0.05), and number of central sleep apnea (CSA) (7.8 ± 2.6 vs 3.0 ± 1.3/hour, P = 0.03), but not number of obstructive sleep apnea (OSA, 8.6 ± 3.3 vs 7.2 ± 2.3/hour, P = 0.65) compared to baseline. Percentage change in PASP was significantly correlated with percentage changes in LVEF (r=?0.57, P = 0.04), AHI (r = 0.5, P = 0.05), and number of CSA episodes (r = 0.55, P = 0.02). Conclusions: The results demonstrated that CRT significantly reduces CSA in patients with HF. Importantly, we have noted a decrement of PASP correlated to drop in CSA which maybe one of the mechanisms explaining this observation. Future studies are required to confirm our finding and elucidate other possible mechanisms in this regard.     

A population analysis of the DGAT1 inhibitor GSK3008356 and its effect on endogenous and meal‐induced triglyceride turnover in healthy subjects

Non‐alcoholic steatohepatitis (NASH) is a liver disease in which fatty infiltration is accompanied by liver inflammation. GSK3008356 is under development as a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme involved in the formation of triglyceride (TG). Decreased DGAT1 activity can reduce circulating TG and liver TG, and therefore could potentially prevent or treat NASH. The aim of the current study was to develop a population pharmacokinetic–pharmacodynamic (PKPD) model that characterizes the PK disposition of GSK3008356 and its relation to the changes in blood TG. Drug concentrations were measured in 104 healthy adults receiving various single (SD) and repeat doses (RD) in a first time in human (FiH) study. A 30% fat meal was given at hour 2 postdose, and blood postprandial TG concentrations were measured at various time points. The population PKPD model consists of several parts including a PK model, drug effect model, meal effect model, and a turnover model. The pharmacokinetic data were described using a 3‐compartment model. Drug effect was described by an inhibitory sigmoidal Emax model. Since TG levels change with the introduction of a meal, a bi‐exponential meal effect model was utilized. The total change in TG was fitted using a turnover model with drug and meal effects on the TG production rate. The current analysis presents a PKPD modeling strategy of time‐varying TG data coming from both endogenous and exogenous sources. In general, the presented model could be utilized in the model‐based drug development of drugs that influence TG levels in blood.     

The genetic influences on oxycodone response characteristics in human experimental pain

Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu‐, kappa‐ and delta‐opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single‐nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.     

Single Transseptal Big Cryoballoon Pulmonary Vein Isolation using an Inner Lumen Mapping Catheter

Background: The single big cryoballon technique for pulmonary vein isolation (PVI) has been limited by the need for two transseptal punctures (TP). We therefore investigated feasibility and safety of a simplified approach using a single TP and a novel circumferential mapping catheter (CMC). Methods: Patients underwent 28‐mm cryoballoon PVI using a single TP. The CMC (Achieve^© Medtronic Inc., Minneapolis, MN, USA) served as (1) guidewire and (2) as a PV mapping tool. Primary endpoint was PVI without switching to a regular guidewire. Secondary endpoints included: (1) PV signal quality during freezing, (2) time to PVI, (3) classification of successful ablation technique, (4) complications, and (5) procedural data. Results: A total of 32 patients (126 PVs) were studied (mean age: 62 ± 11 years, 24 males, left atrium: 40 ± 4 mm). The primary endpoint was achieved in 29/32 patients (91%) and 123/126 PVs (98%) with a procedure and fluoroscopy time of 126 ± 26 minutes and 18.9 ± 7.5 minutes, respectively. Real‐time visualization of PVI could be observed in 61/126 (48%) PVs. Time to sustained PVI versus nonsustained PVI was 66 ± 56 seconds versus 129 ± 76 seconds (P < 0.001). One phrenic nerve palsy was observed. After a follow‐up of 250 ± 84 days 23/32 patients (72%) remained in sinus rhythm. Conclusion: The “simplified single big cryoballoon” PVI strategy appears to be safe and feasible. However, real‐time PV recording was achieved in <50% of PVs. Therefore, further catheter refinements are warranted. (PACE 2012; 35:1304–1311)     

Developing nursing research in the United Arab Emirates: a narrative review

Aim

This article identified, critically analysed and synthesized the literature on international nursing and midwifery research capacity building and standards.

Background

The United Arab Emirates is heavily dependent up on expatriate nurses. Only 4% of nurses working within the country are Emirati. The nation is therefore committed to developing nurses and nursing as a profession.

Introduction

The United Arab Emirates’ Nursing and Midwifery Council was formed in 2009 and initially focused on regulation, education and specialization. This review was undertaken to inform the work of the Council's newly established Scientific Research Sub‐Committee.

Methods

A rapid narrative review was conducted using the Cumulative Index of Nursing and Allied Health Literature database, key words, Boolean operators, parameters and a journal‐specific search. An inclusion/exclusion criterion was identified.

Results

The search provided 332 articles with 45 included in the final review. The literature on nursing research ‘standards’ and ‘capacity building’ is diverse and inconsistent across continents and in approaches.

Discussion

Nursing research has evolved to varying degrees across the globe. Nevertheless, irrespective of the locale, there are similar problems encountered in growing research, for example nursing faculty shortage, lack of collaborative research, funding. There are also specific challenges in the Middle East and North Africa region.

Limitations

The review was constrained by time and access.

Conclusion and implications for nursing policy

There are specific challenges for the United Arab Emirates. However, the country is well placed to learn from the experiences of colleagues elsewhere. Time and commitment is required to build the solid foundations necessary to ensure robust, sustained growth. Identifying research capacity as both a process and outcome at the outset may also assist. Further, it may be prudent to consider initiating a Gulf Coast Countries’ collaborative approach to building research capacity to harness scare resources and create a larger critical mass.     

Evolution of the neural sex‐determination system in insects: does fruitless homologue regulate neural sexual dimorphism in basal insects?

In the brain of holometabolous insects such as the fruit fly Drosophila melanogaster, the fruitless gene produces sex‐specific gene products under the control of the sex‐specific splicing cascade and contributes to the formation of the sexually dimorphic circuits. Similar sex‐specific gene products of fruitless homologues have been identified in other holometabolous insects such as mosquitoes and a parasitic wasp, suggesting the fruitless‐dependent neural sex‐determination system is widely conserved amongst holometabolous insects. However, it remains obscure whether the fruitless‐dependent neural sex‐determination system is present in basal hemimetabolous insects. To address this issue, identification, characterization, and expression analyses of the fruitless homologue were conducted in the two‐spotted cricket, Gryllus bimaculatus, as a model hemimetabolous insect. The Gryllus fruitless gene encodes multiple isoforms with a unique zinc finger domain, and does not encode a sex‐specific gene product. The Gryllus Fruitless protein is broadly expressed in the neurones and glial cells in the brain, and there was no prominent sex‐related difference in the expression levels of Gryllus fruitless isoforms. The results suggest that the Gryllus fruitless gene is not involved in the neural sex‐determination in the cricket brain.