Determinants of Hospital-based Physician Participation in Quality Improvement: A Survey of Hospitalists in British Columbia, Canada.

Objective: We aimed to understand the extent of hospitalist involvement in system improvement efforts across the province of British Columbia in Canada and provide insights into determinants of such participation. Materials and Methods: We designed a web-based survey and asked about individual, programmatic, and institutional characteristics that may facilitate or impair hospitalist involvement in quality improvement (QI) activities. The survey was sent to all individuals who participated in "hospitalist care" from January 2014 to February 2015, in the province of British Columbia, Canada. We conducted both quantitative and qualitative analysis of responses. Results: We received 57 complete responses to the survey of 322 invited individuals (17.7% response rate). Of these, 15 individuals (26.3%) indicated that they had participated in QI initiatives. Respondents highlighted high clinical workload and lack of time, lack of QI skills and training, lack of access to performance data, poor support from hospital/health authority administration, and lack of financial compensation as main barriers to QI involvement. These themes were also supported in logistic regression, where QI training and the number of weeks worked as a hospitalist showed significant predictive properties for involvement in QI initiatives. Conclusion: Our study attempts to understand the various individual or organizational attributes that could facilitate involvement by hospital-based generalist physicians in QI activities. Our findings show lack of formal QI training is an important barrier for hospitalist involvement in QI, and highlight the need for formal training, dedicated time, support from physician leadership, and financial incentive as important facilitators for participation in systemic improvement efforts.

Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome.

AIMS: Brugada syndrome (BrS) is associated with increased risk for atrial fibrillation (AFib). However, the role of SCN5A mutations in the occurrence of AFib remains unclear. Cardiac sodium current reduction caused by SCN5A mutations may facilitate AFib by slowing intra-atrial conduction and inducing structural changes, but also prevent it by suppressing atrial ectopic activity. Here, we examined the relation between SCN5A mutations, atrial conduction velocity, atrial structural changes, and atrial ectopic activity in BrS. METHODS AND RESULTS: Data from 214 BrS patients [78 with an SCN5A mutation (patients with an SCN5A mutation, BrSSCN5A+) and 136 without an SCN5A mutation (patients without an SCN5A mutation, BrSSCN5A-)] were collected. Intra-atrial conduction velocity was assessed by measuring P-wave durations at baseline and during sodium channel provocation testing. Atrial structural changes were assessed by measuring atrial dimensions using cardiac magnetic resonance imaging. Atrial ectopic activity was assessed by determining the incidence of atrial ectopic beats using 24 h Holter recordings. Clinical characteristics (including AFib occurrence) did not differ between BrSSCN5A+ and BrSSCN5A-. Baseline P-wave durations were longer in BrSSCN5A+ than in BrSSCN5A-, but lengthened markedly in BrSSCN5A- during provocation testing. Atrial dimensions did not differ. Atrial ectopic beats occurred more often in BrSSCN5A-, and the proportion of patients experiencing one or more atrial ectopic beats was larger in BrSSCN5A- than in BrSSCN5A+. CONCLUSION: In BrS, the presence of an SCN5A mutation is associated with intra-atrial conduction slowing and suppressed atrial ectopic activity. Intra-atrial conduction slowing may provide a plausible substrate for AFib maintenance, while reduced atrial ectopic activity may constitute inhibition of the trigger for AFib initiation.

Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole-induced seizures in mice.

In the present study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were assessed in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. Tramadol was administered intraperitoneally (0.5-50mg/kg) 30 minutes prior to induction of seizures. The effects of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5, 1, 5, and 10mg/kg), the nitric oxide precursor L-arginine (10, 30, and 60 mg/kg), and the nonspecific opioid receptor antagonist naloxone (0.1, 0.5, 1, and 5mg/kg) on the anticonvulsant effect of tramadol were investigated. Administration of tramadol (1mg/kg) increased the threshold for seizures induced with PTZ in a monophasic, dose-independent, and time-dependent manner. Acute administration of L-NAME (5 and 10mg/kg) inhibited the anticonvulsant effect of tramadol (1mg/kg), whereas L-arginine, in the noneffective dose range (30 and 60 mg/kg), potentiated the seizure threshold when co-administered with a subeffective dose of tramadol (0.5mg/kg). Naloxone partially and dose-independently antagonized the anticonvulsant effect of tramadol (1mg/kg). These results indicate that the anticonvulsant effect of tramadol is mediated by the nitric oxide pathway and also by classic opioid receptors.

Tocolytic effect of delta9-tetrahydrocannabinol in mice model of lipopolysaccharide--induced preterm delivery: role of nitric oxide.

INTRODUCTION: In this study, we explained that exogenous cannabinoid, Delta(9)-tetrahydrocannabinol (THC), has a preventive effect in a murine model of lipopolysaccharide (LPS)-induced preterm delivery and the contribution of nitric oxide (NO) pathway as a mechanism involved in this process. STUDY DESIGN: Preterm delivery was induced by double dose of 35 microg/kg LPS with 3-hour interval on gestational day (gd) 15. Delta(9)-tetrahydrocannabinol was administered with (a) double dose (0.02, 0.05, 0.1, 0.5, 1, and 5 mg/kg) 1 hour before each LPS injection, on gd 15 and (b) single administration (0.05, 0.1, and 0.5 mg/kg,) on gds 13 and 14, and the double administration, 1 hour before each LPS injection. To assess the involved mechanism, either AM281 (CB1 receptor antagonist, 2 mg/kg) and AM630 (CB2 receptor antagonist, 5 mg/kg) or N(omega)-nitro-L-arginine methyl ester (L-NAME, 2 mg/kg) was administered 1 hour before each THC injection on gds 13, 14, and 15. The main outcome measurement was the incidence of preterm delivery after injection of last LPS dose. Any interaction in the incidence and time of preterm delivery was ruled out by administration of AM281, AM630, or L-NAME alone. RESULTS: Chronic THC treatment (0.5 mg/kg) significantly decreased the incidence of LPS-induced premature labor and increased the delivery time. Both AM281 and L-NAME reversed THC-induced attenuation of preterm delivery rate and pregnancy duration. Unlike AM281, AM630 did not influence the rate of preterm delivery in THC-treated mice. CONCLUSION: Delta(9)-Tetrahydrocannabinol contributes to the regulation of gestational duration in LPS-induced preterm delivery probably by NO coupling through the CB1 receptor.

Cardiac sodium channelopathies.

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting alpha-subunit, or in genes that encode the ancillary beta-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce INa decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced INa dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies.

Amelia, cleft lip, and holoprosencephaly: a distinct entity.

We report on a male fetus with amelia, cleft lip, and holoprosencephaly. We compare the clinical findings in our patient with those of previously reported cases with the most clinical overlap. To date only four cases with bilateral limb amelia, CNS anomalies, and facial clefts have been described. Our report appears to represent the fifth case with such a combination of anomalies.

Craniosynostosis in a patient with 2q37.3 deletion 5q34 duplication: association of extra copy of MSX2 with craniosynostosis.

We report on a 1-year-old boy with craniosynostosis, microcephaly, developmental delay and dysmorphic features. Chromosomal studies of the proband showed 46,XY,add(2)(q37)dn and those of the parents were normal. The rearranged material in the patient was further defined using array comparative genomic hybridization (array CGH), which revealed loss of 2Mb distal to 2q37.3 and duplication of 15Mb from 5q34 --> qter. Fluorescence in situ hybridization (FISH) studies using subtelomeric 2q and 5q probes showed the 2q deletion and 5q duplication resulting from a rearrangement of the segment from 5q onto the long arm of chromosome 2. FISH studies of the parents did not show any rearrangement. Recently it has been proposed that an extra copy of MSX2 that maps to 5q35.2 causes premature synostosis of the sutures via the MSX2-mediated pathway of calvarial osteogenic differentiation. Our case further supports the role of MSX2 duplication in the etiology of craniosynostosis.