Oseltamivir Resistance and Antiviral Use

H1N1 Update: Oseltamivir Resistance and Antiviral Use

The CDC reports oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two children who received prophylaxis and provides revised recommendations for antiviral use during the 2009 flu season.

Although sporadic cases of oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection have been reported, oseltamivir remains an important tool in our armamentarium against flu. In July 2009, two girls residing in the same camp cabin in North Carolina developed oseltamivir-resistant 2009 (H1N1) virus infection while receiving oseltamivir as part of a mass prophylaxis program during an influenza outbreak. Both girls recovered fully. Whether the one girl case transmitted the virus to the other or whether both girls were infected by another camper is uncertain. One girl continued to receive prophylactic (not therapeutic) doses of oseltamivir during the first 4 days of her illness, which could have contributed to the development of resistance.

On September 8, 2009, the CDC updated recommendations for use of antiviral medications in the treatment and prevention of influenza for the 2009–2010 influenza season.
The new recommendations include the following additions aimed at reducing the likelihood of resistance and ensuring adequate antiviral drug supplies:

• Do not use antivirals for postexposure chemoprophylaxis in healthy children or adults to manage outbreaks in the community, school, camp, or other settings.
• Age-based dosing recommendations are provided for children younger than 1 year.
  

For high-risk individuals, consider:

• Increased use of preemptive therapy after exposure with an emphasis on prompt treatment of symptomatic people in lieu of prophylaxis. (Remember that the doses for prophylaxis and therapy are different.)
• Establishing systems to ensure rapid access to antiviral therapy when needed (e.g., providing telephone consultation and prescriptions after office hours or giving prescriptions to patients to fill if needed only after speaking with a physician).
  

Comment:
Pandemic influenza poses multiple challenges related to the frequency of changes in information and recommendations. These case reports and recommendations highlight the need for judicious use of antivirals in otherwise healthy individuals and rapid access to appropriate therapy in high-risk patients. Antiviral therapy is most effective when started within 48 hours after the onset of symptoms. Vaccination (when available) remains the mainstay of prevention and is far preferable to prophylaxis.

—
Peggy Sue Weintrub, MD

Dr. Weintrub is on the Speakers' Bureau for MedImmune (maker of FluMist) and Sanofi-Aventis (makers of standard flu vaccine).
Published in Journal Watch Pediatrics and Adolescent Medicine September 16, 2009

Citation(s):
Centers for Disease Control and Prevention (CDC). Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis — North Carolina, 2009. MMWR Morb Mortal Wkly Rep 2009 Sep 11; 58:969.

Centers for Disease Control and Prevention (CDC). Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. Sep 8 , 2009. (http://www.cdc.gov/h1n1flu/recommendations.htm)

Aortic dissection 要用什麼檢查？

CTA, MRA, and TEE are all highly sensitive and specific modalities for diagnosing aortic dissection. Therefore, the condition of the patient, the information needed, and the resources and expertise immediately available should drive the choice of study. MRA is considered the gold standard diagnostic study and is the preferred modality for hemodynamically stable patients with suspected aortic dissection. Because of slow data acquisition and the inaccessibility of patients in the scanner, it is generally unsuited for unstable patients, including those with ongoing pain. Bedside TEE is an excellent choice for patients who are too unstable for MRA but is less effective at visualizing distal dissections. Arch aortography is generally reserved for the confirmation of questionable diagnoses or to image specific branch arteries.

簡單說：

• 病人穩定：MRI 是金標準。
• 病人不穩定：CTA 是金標準。
• 病人不穩定又不能做CTA時：TEE是金標準。
• CTA較難看清楚的地方(尤其是分枝處)：用aortogram來輔助。

很棒的全文：
http://www3.interscience.wiley.com/cgi-bin/fulltext/112585678/PDFSTART

ACGME 六大核心能力

1. 病人照護 (Patient care)
2. 醫學知識 (Medical knowledge)
3. 從工作中學習及成長 (Practice-based learning and improving)
4. 人際及溝通技能 (Interpersonal and communication skills)
5. 制度下的臨床工作 (System-based practice)
6. 專業素養 (Professionalism)

COPD使用吸入性類固醇不增加肺炎機率

Inhaled Steroids in COPD: Is Risk for Pneumonia Really Higher?
Risk was not elevated in patients who received budesonide.

Do inhaled corticosteroids elevate risk for pneumonia in patients with chronic obstructive pulmonary disease? Several clinical trials, observational studies, and meta-analyses suggest that they do, by as much as 70%. But, in other trials, researchers have reported lower risk, and previous meta-analyses have been criticized for methodological weaknesses, such as combining trials of inhaled budesonide with those of fluticasone.

Canadian researchers pooled patient-level data from seven large clinical trials in which more than 7000 patients with COPD were randomized to inhaled budesonide or placebo, with or without the long-acting β2-agonist formoterol, for 6 to 12 months. In both groups, 3% of patients developed pneumonia; in 1% of budesonide recipients and in 2% of placebo recipients, it was a serious adverse event (i.e., causing hospitalization or death), with no significant difference between groups, before or after adjustment for potential confounders.

Comment: Budesonide is cleared more rapidly from the airways than fluticasone, and the authors speculate that this fact could help explain why pneumonia risk is not elevated with budesonide (as it seems to be with fluticasone). Surprisingly, despite high mortality associated with community-acquired pneumonia, no study has shown that fatal pneumonia is more common among patients who receive inhaled steroids, which suggests that pneumonias induced by inhaled steroids are relatively mild. An editorialist concludes that the benefits of inhaled steroids in COPD patients continue to outweigh the risks substantially.

—
Bruce Soloway, MD

Published in Journal Watch General Medicine September 8, 2009

• Sin DD et al. Budesonide and the risk of pneumonia: A meta-analysis of individual patient data. Lancet 2009 Aug 29; 374:712.
• Welte T. Inhaled corticosteroids in COPD and the risk of pneumonia. Lancet 2009 Aug 29; 374:668.

疾管局H1N1治療指引

http://jack119.org/jackdocs/H1N1_CDC_guidelines2009sep.pdf

Apical Ballooning Syndrome

Features of Apical Ballooning Syndrome
Apical ballooning syndrome (also described as tako-tsubo cardiomyopathy, stress-induced cardiomyopathy, and the broken-heart syndrome) is an increasingly recognized condition that can closely mimic acute myocardial infarction. Its incidence is estimated to be 1 to 2% among patients who present with a presumed acute myocardial infarction. It classically affects postmenopausal women in the fifth to seventh decade, and the onset of the condition is often precipitated by emotional stress. Key features of apical ballooning syndrome are the absence of obstructive coronary artery disease in the setting of characteristic “ballooning” of the left ventricle from severe anteroapical akinesis and hypercontractility of the basal segments. Heart failure is present in approximately 50% of patients with apical ballooning syndrome, and cardiogenic shock occurs in up to 15%. Approximately 20% of these patients also have a transient systolic murmur associated with subvalvular pressure gradients that can mimic hypertrophic obstructive cardiomyopathy.

Diagnosis of Apical Ballooning Syndrome
Although it is critical to differentiate apical ballooning syndrome from acute myocardial infarction quickly, it can be challenging to do so. There are no electrocardiographic findings that clearly distinguish apical ballooning syndrome from acute myocardial infarction. With apical ballooning syndrome, the elevations in troponin are typically much lower than would be expected on the basis of the wall-motion abnormalities. However, it is difficult to rely on cardiac biomarkers alone, since these are often only modestly elevated during the early stages of an acute myocardial infarction. Thus, the diagnosis frequently becomes evident only in the cardiac catheterization laboratory, when no angiographically significant coronary artery disease is found. It is generally not advisable to withhold antithrombotic treatments such as heparin and aspirin while the diagnosis remains uncertain, since acute myocardial infarction is much more common. Decisions about fibrinolytic therapy are more complicated, given its associated risk of intracerebral hemorrhage. Whenever feasible, emergency coronary angiography should be performed to assist in clinical decision making.

What is the pathophysiology of apical ballooning syndrome?
A: The pathophysiology of apical ballooning syndrome has not been clearly elucidated. Leading hypotheses include transient catecholamine toxicity, aborted ST-elevation myocardial infarction with spontaneous lysis of thrombus, coronary vasospasm, and microcirculatory dysfunction. Similar wall-motion abnormalities have been seen in other states of catecholamine excess, such as subarachnoid hemorrhage and pheochromocytoma.

What is the recommended treatment for apical ballooning syndrome?
A: In patients with acute outflow tract obstruction, treatment should focus on ensuring adequate intravascular volume. Beta-blockers may also be considered in an attempt to slow the heart rate and increase the diastolic filling time. Although data from clinical trials are scant, some experts suggest treating patients with apical ballooning syndrome with beta-blockers and angiotensin-converting–enzyme inhibitors until left ventricular systolic function normalizes; it has also been hypothesized that treatment with beta-blockers may reduce the risk of recurrence (which is reported in a case series to be approximately 10%). Inotropic agents should be avoided, since they may exacerbate the outflow tract gradient. Aspirin should be considered for patients who have coexisting coronary artery disease. Some clinicians recommend anticoagulation with warfarin for several weeks in patients with severe systolic dysfunction in order to prevent left ventricular thrombus formation. In most patients with apical ballooning syndrome, the condition improves rapidly with supportive measures. Complete recovery of systolic function is typically observed within 4 to 6 weeks, and the overall prognosis tends to be excellent.

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NEJM - Vol. 361, No. 10, September 3, 2009