Hypoplastic Coronary Artery Disease Presenting with Ventricular Fibrillation Cardiac Arrest.

Hypoplastic coronary artery disease is a rare congenital anomaly that may present with ischaemic heart disease, heart failure or sudden cardiac death (SCD). We describe a case of cardiac arrest in a healthy young man. Work-up revealed a hypoplastic left anterior descending artery. The patient underwent cardioverter-defibrillator implantation for secondary prevention. LEARNING POINTS: Hypoplastic coronary artery disease (HCAD) is a rare cause of cardiac arrest and should be suspected in cases of sudden cardiac death (SCD) in young adults.The mechanism in HCAD leading to ventricular fibrillation cardiac arrest is not well understood.Implantable cardioverter-defibrillator (ICD) implantation is recommended for secondary prevention of ventricular fibrillation.

Designing teacher professional development programs to support a rapid shift to digital.

From a design perspective, this paper offers a response to the impact, value, and application of a manuscript published by Philipsen et al. (Improving teacher professional development for online and blended learning: A systematic meta-aggregative review. Educational Technology and Research Development, 67, 1145-1174. 10.1007/s11423-019-09645-8, 2019). Philipsen et al. (2019) reviewed what constitutes an effective teacher professional development program (TPD) for online and blended learning (OBL), with our response focusing on its value and application in light of an emergency shift to digital to address a global pandemic. This paper also proceeds to examine limitations in previous research into the subject and future research opportunities to investigate important components that inform the design of a resilient and scalable TPD for OBL.

Challenges for Managed Care from 340B Contract Pharmacies.

The federal 340B Drug Pricing Program has expanded rapidly, with important yet still unmeasured impact on both managed care practice and policies. Notably, providers increasingly rely on external, contract pharmacies to extend 340B pricing to a broad set of patients. In 2014, 1 in 4 U.S. retail, mail, and specialty pharmacy locations acted as contract pharmacies for 340B-covered entities. This commentary discusses crucial ways in which 340B growth is affecting managed care pharmacy through formulary rebates, profits from managed care paid prescriptions, disruption of retail pharmacy networks, and reduced generic dispensing rates. Managed care should become more engaged in the discussion on how the 340B program should evolve and offer policy proposals to mitigate the challenges being encountered. There is also an urgent need for objective, transparent research on the 340B program's costs, benefits, and implications for managed care pharmacy and practice.

National trends in spending on and use of oral oncologics, first quarter 2006 through third quarter 2011.

Oral prescription drugs are an increasingly important treatment option for cancer. Yet contemporaneous US trends in spending on anticancer drugs known as oral oncologics have not been described. Using nationally representative data, we describe trends in national spending on and use of forty-seven oral oncologics between the first quarter of 2006 and the third quarter of 2011. Average quarterly national spending on oral oncologics increased 37 percent, from $940.3 million to $1.4 billion in 2012 dollars, a significant change. Average quarterly use of oral oncologics in the same time period measured in extended units increased at a significant pace but more slowly than spending (10 percent). Within this broader trend, differences in spending among categories of oral oncologics were observed. High levels of and increases in both spending and use were concentrated among new brand-name and patent-protected oral oncologics, including second-generation tyrosine kinase inhibitors used to treat chronic myelogenous leukemia. Decreased spending but increased use was observed among oral oncologics that lost patent protection during the study period and were available in generic form, including hormonal therapies used to treat breast and prostate cancers. Spending on new and patent-protected oral oncologics and associated price increases are significant drivers of increased spending.

Prevalence of guideline-directed medical therapy among patients receiving cardiac resynchronization therapy defibrillator implantation in the National Cardiovascular Data Registry during the years 2006 to 2008.

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality among selected patients with left ventricular systolic dysfunction and severe heart failure symptoms despite guideline-directed medical therapy (GDMT). Contemporaneous guidelines provided clear recommendations regarding selection of patients for CRT, including that all patients should first receive GDMT with ß blockers and renin-angiotensin axis antagonists. Prevalence of GDMT among real-world patients receiving CRT defibrillators (CRT-D) has not been well studied. We identified 45,392 patients in the National Cardiovascular Data Registry Implantable Cardioverter-Defibrillator Registry who underwent first CRT-D implantation for primary prevention of sudden death from January 2006 to June 2008. We calculated the proportion of patients with contemporaneous class I guideline indications for CRT-D, the proportion receiving GDMT for heart failure, and the proportion receiving GDMT who had class I guideline indications for CRT-D. Among patients without contraindications, 87% were prescribed ß blockers, 78% an angiotensin-converting enzyme inhibitor or an angiotensin II receptor inhibitor, and 70% both a ß blocker and an angiotensin-converting enzyme or angiotensin II receptor inhibitor at discharge. Finally, 50% of patients met class I guideline indications and were prescribed GDMT at discharge; 9% neither met class I indications nor were prescribed GDMT at discharge. The major limitation of this study is the lack of dosage information in the Implantable Cardioverter-Defibrillator Registry and lack of prescribing information at times other than discharge. In conclusion, many patients receiving CRT-D are not receiving GDMT at discharge. Ensuring that all patients receiving CRT-D are also receiving GDMT appears to be a quality improvement target.

Treatment of obstructive sleep apnea reduces the risk of atrial fibrillation recurrence after catheter ablation.

OBJECTIVES: The aim of this study was to examine the effect of continuous positive airway pressure (CPAP) therapy on atrial fibrillation (AF) recurrence in patients with obstructive sleep apnea (OSA) undergoing pulmonary vein isolation (PVI). BACKGROUND: OSA is a predictor of AF recurrence following PVI. However, the impact of CPAP therapy on PVI outcome in patients with OSA is poorly known. METHODS: Among 426 patients who underwent PVI between 2007 and 2010, 62 patients had a polysomnography-confirmed diagnosis of OSA. While 32 patients were "CPAP users" the remaining 30 patients were "CPAP nonusers." The recurrence of any atrial tachyarrhythmia, use of antiarrhythmic drugs, and need for repeat ablations were compared between the groups during a follow-up period of 12 months. Additionally, the outcome of patients with OSA was compared to a group of patients from the same PVI cohort without OSA. RESULTS: CPAP therapy resulted in higher AF-free survival rate (71.9% vs. 36.7%; p = 0.01) and AF-free survival off antiarrhythmic drugs or repeat ablation following PVI (65.6% vs. 33.3%; p = 0.02). AF recurrence rate of CPAP-treated patients was similar to a group of patients without OSA (HR: 0.7, p = 0.46). AF recurrence following PVI in CPAP nonuser patients was significantly higher (HR: 2.4, p < 0.02) and similar to that of OSA patients managed medically without ablation (HR: 2.1, p = 0.68). CONCLUSIONS: CPAP is an important therapy in OSA patients undergoing PVI that improves arrhythmia free survival. PVI offers limited value to OSA patients not treated with CPAP.

Prevalence and predictors of off-label use of cardiac resynchronization therapy in patients enrolled in the National Cardiovascular Data Registry Implantable Cardiac-Defibrillator Registry.

OBJECTIVES: The purpose of the study was to define the extent and nature of cardiac resynchronization therapy (CRT) device usage outside consensus guidelines using national data. BACKGROUND: Recent literature has shown that the application of CRT in clinical practice frequently does not adhere to evidence-based consensus guidelines. Factors underlying these practices have not been fully explored. METHODS: From the National Cardiovascular Data Registry's Implantable Cardiac-Defibrillator Registry, we defined a cohort of 45,392 cardiac resynchronization therapy-defibrillator (CRT-D) implants between January 2006 and June 2008 with a primary prevention indication. We defined "off-label" implants as those in which the ejection fraction was >35%, the New York Heart Association functional class was below III, or the QRS interval duration was <120 ms in the absence of a documented need for ventricular pacing. The relationships between patient, implanting physician, and hospital characteristics with off-label use were explored with multivariable hierarchical logistic regression models. RESULTS: Overall, 23.7% of devices were placed without meeting all 3 implant criteria, most often due to New York Heart Association functional class below III (13.1% of implants) or QRS interval duration <120 ms (12.0%). Atrial fibrillation/flutter, previous percutaneous coronary intervention, and the performance of an electrophysiology study before implant were independently associated with increased odds of off-label use, whereas diabetes mellitus, increasing age, and female sex were associated with decreased odds. Physician training and insurance payer were weakly associated with the likelihood of off-label use. CONCLUSIONS: Nearly 1 in 4 patients receiving CRT devices in the study time frame did not meet guideline-based indications. Given the evolving evidence base supporting the use of CRT, these practices require careful scrutiny.

PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis.

K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-Ras interacts with Bcl-XL. PKC agonists promote apoptosis of cells transformed with oncogenic K-Ras in a S181-dependent manner. K-Ras with a phosphomimetic residue at position 181 induces apoptosis via a pathway that requires Bcl-XL. The PKC agonist bryostatin-1 inhibited the growth in vitro and in vivo of cells transformed with oncogenic K-Ras in a S181-dependent fashion. These data demonstrate that the location and function of K-Ras are regulated directly by PKC and suggest an approach to therapy of K-Ras-dependent tumors with agents that stimulate phosphorylation of S181.