Syncope, Widened QRS Interval, and Left Ventricular Systolic Depression Coincident with Propafenone Therapy for Atrial Fibrillation.

Samaan RA, Sobamowo HO, Tamburrino F, Grodman R, Isber N.

Cardiology Division, Department of Medicine, Richmond University Medical Center, Staten Island, New York 10310.

Abstract

We report the case of a 46-year-old man who developed syncope, a widened QRS interval, and depressed left ventricular systolic function during propafenone therapy for atrial fibrillation. These acute findings may have been consequent to an increased dosage of propafenone combined with heavy alcohol consumption that led to decreased metabolism of propafenone. In addition, propafenone is known to interfere with liver function, although this patient's test results showed scant evidence of liver abnormalities. Yet another possible factor is the genetic spectrum in the metabolism of propafenone and other class I antiarrhythmic agents. When propafenone is prescribed, we recommend advising patients that alcohol consumption and interactions with other drugs can lead to increased levels of the antiarrhythmic agent, with resultant toxicity that can lead to adverse cardiovascular effects. Patients taking propafenone should also undergo periodic liver function testing. Finally, attention should be paid to voluntary or official recalls of specific antiarrhythmic medications that are of unreliable quality or potency.

PMID: 20844627

Subject: Burnout associated with self-reported unprofessional conduct among medical students

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ScienceDaily (Sep. 14, 2010) — Medical students with higher levels of distress (burnout) were more likely to self-report unprofessional conduct related to patient care and less altruistic professional values, according to a study in the September 15 issue of JAMA, a theme issue on medical education.

"Professionalism is a core competency for all physicians. Professionalism includes being honest, acting with integrity, advocating for the needs of patients, reducing barriers to equitable health care, and adhering to an ethical code of conduct," the authors write. "Despite the widely acknowledged importance of professionalism, how personal distress (such as depression or low mental quality of life [QOL]) and professional distress (such as burnout) relate to professionalism is largely unexplored."

Liselotte N. Dyrbye, M.D., M.H.P.E., of the Mayo Clinic College of Medicine, Rochester, Minn., and colleagues conducted a study that measured multiple dimensions of professionalism and assessed its relationship to burnout and other measures of distress. The study included a survey of all medical students attending 7 U.S. medical schools (overall response rate, 2,682/4,400 [61 percent]) in the spring of 2009. Items measured and assessed in the survey included burnout, depression, quality of life, as well as items exploring students' personal engagement in unprofessional conduct, understanding of appropriate relationships with industry, and attitudes regarding physicians' responsibility to society. Among the outcomes assessed included frequency of self-reported cheating/dishonest behaviors and understanding of appropriate relationships with industry as defined by American Medical Association (AMA) policy.

Of the students who responded to the inventory regarding burnout, 1,354 of 2,566 (52.8 percent) had burnout. The researchers found that cheating/dishonest academic behaviors were rare (endorsed by less than 10 percent) in comparison to unprofessional conduct related to patient care (endorsed by up to 43 percent). Only 14 percent (362/2,531) of students' opinions on relationships with industry aligned with the AMA policy for 6 scenarios.

Students with burnout were significantly more likely to have engaged in each of the cheating/dishonest clinical behaviors evaluated (with the exception of taking credit for another person's work), such as copying from a crib sheet or from another student during an exam; or reporting a physical examination finding as normal when it had been omitted. Students with burnout were more likely to report engaging in 1 or more unprofessional behaviors than those without burnout (35.0 percent vs. 21.9 percent). Burned-out students were also less likely to hold altruistic views regarding physicians' responsibility to society, including personally wanting to provide care for the medically underserved (79.3 percent vs. 85.0 percent).

"Burnout was the only aspect of distress independently associated with report of 1 or more cheating/ dishonest clinical behaviors or with disagreeing with 1 or more altruistic attitudes regarding physicians' responsibility to society after adjusting for demographic characteristics (sex, age, parental status, marital status, year in school, student debt load), burnout, positive depression screen, mental QOL, and physical QOL," the authors write.

"In this large, multi-institutional study, self-reported cheating and dishonest clinical behaviors showed a direct association with burnout, while altruistic professional values regarding physicians' responsibility to society showed an inverse relationship with burnout," the researchers write. "In addition to exploring these associations further, future research should investigate whether interventions designed to reduce burnout help students cultivate professional values and behavior."

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Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by JAMA and Archives Journals.

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Journal Reference:

1. Liselotte N. Dyrbye; F. Stanford Massie, Jr; Anne Eacker; William Harper; David Power; Steven J. Durning; Matthew R. Thomas; Christine Moutier; Daniel Satele; Jeff Sloan; Tait D. Shanafelt. Relationship Between Burnout and Professional Conduct and Attitudes Among US Medical Students. JAMA, 2010; 304 (11): 1173-1180 [link]

Note: If no author is given, the source is cited instead.

Palliative Care Training Program Ineffective (CME/CE)

A hospital-based training program designed to improve end-of-life care in the intensive care unit had no effect on quality of dying or quality of care, researchers found.

It also had no effect on the length of time patients spent in the ICU before death or the time from ICU admission to withdrawal of mechanical ventilation, according to J. Randall Curtis, MD, of the University of Washington in Seattle, and colleagues.

The findings come from a cluster-randomized study of 12 Seattle/Tacoma-area hospitals and suggest that improvements in palliative care will need more direct contact with patients and family, Curtis and colleagues argued online in the American Journal of Respiratory and Critical Care Medicine.

"We were surprised that it was a negative study," Curtis said in a statement, because the training program had previously been shown to have a beneficial effect in a single institution.

But the program aimed to change how nurses and doctors delivered care and that proved to be a challenge, he said.

"It is very difficult to change busy critical care clinicians' -- including both nurses and physicians -- behavior patterns, because they have a lot of pressures on them," Curtis said. "While we designed the intervention with that in mind, it was more difficult than we anticipated."

The training program included grand rounds lectures on palliative care, pamphlets aimed at educating both caregivers and families about palliative care, discussions aimed at removing barriers to palliative care, and feedback on the quality of care from both families of patients and the nurses who had attended them.

Also, doctors and nurses had training designed to increase communication skills with one another and with families, and were instructed to discuss end-of-life options with families.

Six hospitals were randomly selected to have the intervention, over a period of 13 to 20 months; the other six served as controls, but got the program after the study ended. Practices at each hospital were also compared before and after the training program.

The primary outcome was family satisfaction with the death of the loved one and secondary outcomes included nurse satisfaction with the care, time in ICU before death, and time to withdrawal of ventilation.

But, the researchers found, there was no effect:

• Family satisfaction was not significantly different, either between active and control hospitals or before and after the training program within each institution.
• Nurse satisfaction did not differ in either case.
• Days in the ICU before death increased slightly in the active hospitals, but did not reach significance (at P=0.07).
• Time to withdrawal of mechanical ventilation, when it was used, did not change.

"We asked whether this intervention could improve families' experience with the death of their loved one in the ICU," Curtis said, "and the answer was no."

Although there are a range of possible explanations for the negative result -- including a relatively low response rate from families of 43% and from nurses of 50% -- the "most plausible explanation for our negative results is that the intervention was ineffective," the authors concluded.

They cautioned that the study had additional limitations, including the time-consuming and expensive nature of the cluster randomization, the difficulty of measuring the "dose" of the intervention, and an unequal distribution of patient characteristics between the active and control groups.

Also, they wrote, the results may not apply elsewhere.

The study was supported by the National Institute of Nursing Research.

The authors said they had no financial conflicts.

Smoking Ban Linked to Drop in Kids' Hospitalization (CME/CE)

Children's hospital admissions for asthma plummeted after passage of a law banning smoking in all enclosed public places and workplaces, a Scottish study found.

Before the Smoking, Health and Social Care (Scotland) Act was implemented in 2006, asthma admissions had increased at a mean annual rate of 5.2% (95% CI 3.9 to 6.6) relative to the rate in January 2000, according to Daniel Mackay, PhD, of the University of Glasgow, and colleagues.

But after the law was enacted, rates of admission fell by 18.2% per year (95% CI 14.7 to 21.8, P<0.001), the researchers reported in the Sept. 16 New England Journal of Medicine.

The legislation was "extremely successful" in its primary aim, which was the reduction of exposure to tobacco smoke in places such as bars, with a pronounced reduction in respiratory ailments among exposed workers.

To see if children -- who would not be subject to workplace exposure -- also benefited, Mackay and colleagues analyzed data on all 21,415 hospital admissions for asthma that occurred in Scotland between January 2000 and October 2009.

The analysis was restricted to children younger than 15 at the time of admission.

The net reduction in hospital admissions was 13% per year (95% CI 10.4 to 15.6), the researchers reported.

After adjustment for confounding variables such as sex, age, socioeconomic status, and urban or rural residence, during the period before the law was implemented admissions increased by 4.4% (95% CI 3.3 to 5.5) compared with the rate in January 2000.

After adjustment for confounding variables, admissions decreased by 19.5% (95% CI 16.5 to 22.4, P<0.001), which meant there was a net reduction of 15.1% each year (95% CI 12.9 to 17.2).

Reductions in admissions were seen in both preschool and school-age children, which fell by 18.4% and 20.8%, respectively.

Before the smoking ban went into effect, there had been concern that environmental exposure among children would increase if adults who could no longer smoke outside the home would smoke more at home.

This did not happen, however, and the legislation actually was followed by increases in voluntary restrictions on household smoking.

Smoking among children themselves also decreased, from 5% among 13-year-old boys in 2004 to 3% in 2007.

That the overall exposure to tobacco smoke among children fell was verified objectively with measurement of salivary cotinine concentrations, the authors noted.

Strengths of the study were the inclusion of data from all areas of Scotland, with consistent results throughout.

Limitations were the inclusion of hospital admissions only, and the researchers' lack of access to data on less severe asthma exacerbations.

They also did not have access to individual measurements of level of exposure so were unable to determine whether the decreases in hospitalizations resulted from changes in exposure in public places, in the home, or in active smoking by children.

The authors concluded that the effects of smoking prohibitions can extend to populations other than those directly targeted.

One author received payments from the U.K. Department of Health, a second received grants and fees from the National Health Service, Scotland, and a third was employed by NHS Health Scotland, the agency that funded the research.

Novel Target For Existing Drug May Improve Success Of Radiation Therapy

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Scientists at Washington University School of Medicine in St. Louis have discovered a new drug target that could improve the effectiveness of radiation for hard-to-treat cancers.The finding, published in the Journal of the National Cancer Institute, focuses on the role of the enzyme cytosolic phospholipase A2 (cPLA2). This enzyme promotes development and functioning of blood vessel networks that feed malignant tumors, enabling them to overcome the effects of radiation.

They have also identified a drug that stops production of the enzyme. Inhibiting the enzyme can stop the flow of blood tumors need to survive.

Cancers thrive and spread thanks to a unique ability to recruit networks of new blood vessels that penetrate into tumors, bringing oxygen and nutrients and potentially transporting cancer cells to other parts of the body.

Cancer cells start the process of new blood vessel construction, called angiogenesis, by releasing specific molecules into surrounding normal tissue, kicking off a cascade of molecular signals that cause cells lining existing blood vessels to divide and create new vessels. These new vessel networks link the tumor to the circulatory system and its life-sustaining cargo.

Lung cancer and glioblastoma, the most common type of primary brain tumor, are particularly adept at inducing new blood vessel creation via angiogenesis. They are also highly resistant to treatment by radiation.

"Our original objective was to measure the signaling molecules that enable lung and brain cancer to be resistant to radiation," says Dennis Hallahan, MD, the Elizabeth H. and James S. McDonnell III Distinguished Professor in Medicine and chair of the Department of Radiation Oncology at the School of Medicine and senior author of the study.

"There are hundreds of signaling molecules, but the enzyme cPLA2 stood out," Hallahan says. "Radiation of tumor cells triggers production of cPLA2 within two minutes and it contributes to tumor survival."

The cPLA2 enzyme is known to regulate the levels of at last three molecules that promote tumor angiogenesis (the creation of new blood vessel networks to feed cancer cells).

The researchers set out to learn if they could enhance the effect of radiation therapy for lung and brain cancers by inhibiting this enzyme.

The idea was to implant tumors into normal mice and into mice that had been genetically engineered to be unable to produce cPLA2 and then compare the effect of radiation therapy on tumor progression in each.

The immense power of cPLA2 became apparent to Hallahan when a graduate student complained that her experiment failed because she could not grow tumors in mice that lacked the gene that produces cPLA2.

"While implanted tumors progressed as expected in normal mice used in the experiment, they were virtually undetectable in cPLA2 deficient mice," Hallahan says. "The 'failed experiment' was actually a significant discovery of the enormous control cPLA2 has in regulating tumor angiogenesis."

The scientists then examined the blood vessels of the cPLA2 deficient mice. While the blood vessels of cPLA2 deficient mice appeared normal, close inspection revealed the absence of a certain type of contractile cell that regulates blood flow.

"Without these cells, blood vessels can still grow into the tumor but blood cannot flow to the tumor," Hallahan says. "Cancer cannot survive without blood flow to feed it."

The central role of cPLA2 in determining the presence or absence of these contractile cells makes it a prime target for interventional therapy.

"Drugs that target cPLA2 have enormous potential for improving the success of radiation against highly angiogenic tumors," Hallahan says.

Hallahan has already identified an existing drug that inhibits cPLA2. It is a compound originally developed by Wyeth, now part of Pfizer, as a treatment for arthritis. The drug had advanced to Phase 2 testing before being discontinued as a potential arthritis treatment.

Reaching Phase 2 testing, however, suggests that a compound has been proven safe, regardless of whether or not it meets performance standards for the specific medical condition for which it was made. These drugs are typically then tested for other uses.

Hallahan learned of the Pfizer compound from an innovative collaboration between Pfizer and Washington University that allows Washington University scientists to view extensive research data on a large array of Pfizer pharmaceutical candidates that are or were in clinical testing.

Don Frail, PhD, chief scientific officer of Pfizer's Indication's Discovery Unit, says the majority of drug candidates tested in development do not give the desired result.

"Yet those drugs that do succeed typically have multiple uses," Frail says. "Hallahan's research has led to an entirely new potential use for one of these compounds in an area of high patient need that otherwise might have been overlooked. This is exactly what our partnership with Washington University is about and is among the first to be funded through the new relationship."

Hallahan is currently partnering with Craig Wegner, PhD, in the Indications Discovery Unit of Pfizer to further understand the pathways impacted by cPLA2 and to evaluate the drug that inhibits its action.

Linkous A, Yazlovitskaya E, Hallahan D. Cytosolic Phospholi pase A2 and Lysophospholipids in Tumor Angiogenesis. Journal of the National Cancer Institute, published online Aug. 23, 2010.

Funding for this research was provided by the National Cancer Institute.

Source:
Washington University in St. Louis

Aorta-Right Atrial Tunnel.

Krishna CS, Baruah DK, Reddy GV, Panigrahi NK, Suman K, Kumar PV.

Departments of Cardiothoracic & Vascular Surgery (Drs. Kumar and Sai Krishna) and Cardiology (Drs. Baruah, Panigrahi, and Reddy), Apollo Heart Institute; and Division of Radio-Diagnosis (Dr. Suman), Vijaya Medical Center; Visakhapatnam 530002, India.

Abstract

Aorta-right atrial tunnel is a vascular channel that originates from one of the sinuses of Valsalva and terminates in either the superior vena cava or the right atrium. The tunnel is classified as anterior or posterior, depending upon its course in relation to the ascending aorta. An origin above the sinotubular ridge differentiates the tunnel from an aneurysm of the sinus of Valsalva, and the absence of myocardial branches differentiates it from a coronary-cameral fistula. Clinical presentation ranges from an asymptomatic precordial murmur to congestive heart failure. The embryologic background and pathogenesis of this lesion are attributable either to an aneurysmal dilation of the sinus nodal artery or to a congenital weakness of the aortic media. In either circumstance, progressive enlargement of the tunnel and ultimate rupture into the low-pressure right atrium could occur under the influence of the systemic pressure.The lesion is diagnosed by use of 2-dimensional echocardiography and cardiac catheterization. Computed tomographic angiography is an additional noninvasive diagnostic tool. The possibility of complications necessitates early therapy, even in asymptomatic patients or those with a hemodynamically insignificant shunt. Available treatments are catheter-based intervention, external ligation under controlled hypotension, or surgical closure with the patient under cardiopulmonary bypass.Herein, we discuss the cases of 2 patients who had this unusual anomaly. We highlight the outcome on follow-up imaging (patient 1) and the identification and safe reimplantation of the coronary artery (patient 2).

PMID: 20844628