TPA for stroke之4.5小時黃金時間

No Benefit from Intravenous Alteplase When Given After 4.5 Hours of Stroke Onset
Risk for favorable outcomes decreases with increasing time to treatment from stroke onset, and, after 4.5 hours, alteplase treatment might increase mortality.

What is the optimal interval between stroke onset and intravenous recombinant tissue plasminogen activator (rt-PA) administration?

Researchers conducted an updated analysis of pooled data from eight trials involving 3670 patients (median age, 68; age range, 19–101) who were randomized to receive rt-PA or placebo within 360 minutes of onset of stroke symptoms.

In multivariate logistic regression analysis, the odds of a favorable 3-month outcome (based on modified Rankin scale score, Barthel index score, and National Institutes of Health Stroke Scale score) were inversely related to time from onset of symptoms to rt-PA treatment, with no treatment benefit after about 270 minutes. Adjusted odds of favorable 3-month outcomes were 2.55 for 0–90 minutes, 1.64 for 91–180 minutes, 1.34 for 181–270 minutes, and 1.22 for 271–360 minutes. Adjusted odds of mortality increased with time to treatment, ranging from 0.78 for 0–90 minutes to 1.49 for 271–360 minutes. Large parenchymal bleeds occurred in 5.2% of rt-PA patients versus 1% of controls and were independent of time-to-treatment interval. The authors conclude that time from stroke onset to treatment should be minimized and that after 4.5 hours, "risk might outweigh benefit." An editorialist adds that, in large middle cerebral artery infarcts, "20 million additional neurons die every 10 min[utes] if reperfusion is not achieved."

Comment:

These data suggest that the risk for favorable outcomes decreases by a factor of about two for every 90-minute delay in treatment from stroke onset and that after 4.5 hours, rt-PA treatment might increase mortality. Lytic therapy for acute stroke must be given at the earliest possible time. Extension of the window for treatment to 4.5 hours is not a license for delay; every minute counts.

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Kristi L. Koenig, MD, FACEP
Published in Journal Watch Emergency Medicine May 28, 2010

Citation(s):
Lees KR et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010 May 15; 375:1695.
Saver JL and Levine SR. Alteplase for ischaemic stroke — Much sooner is much better. Lancet 2010 May 15; 375:1667.

Infectious Mononucleosis

Infectious Mononucleosis

Seroepidemiologic surveys indicate that over 95% of adults worldwide are infected with EBV. In industrialized countries and higher socioeconomic groups, half the population has primary EBV infection between 1 and 5 years of age, with another large percentage becoming infected in the second decade. Because economic and sanitary conditions have improved over past decades, EBV infection in early childhood has become less common, and more children are susceptible as they reach adolescence.

What is the classic triad of presenting signs of infectious mononucleosis?
Pharyngitis (usually subacute in onset), fever, and lymphadenopathy constitute the classic triad of presenting signs of infectious mononucleosis. Sore throat and malaise or fatigue are the most common presenting symptoms. Palatal petechiae, periorbital edema, and rash are less common.

How should infectious mononucleosis be diagnosed?
In the presence of mononucleosis symptoms, a positive heterophile antibody test has a sensitivity of approximately 85% and a specificity of approximately 94% regarding a diagnosis of infectious mononucleosis. However, heterophile antibody tests are negative in 25% of patients during the first week of infection and in 5 to 10% during or after the second week. The detection of at least 10% atypical lymphocytes on a peripheral-blood smear in a patient with mononucleosis has a sensitivity of 75% and specificity of 92% for the diagnosis of infectious mononucleosis. It is reasonable to screen patients who have suspected infectious mononucleosis for group A streptococcal infection with the use of a throat swab and rapid antigen testing or culture.

How is infectious mononucleosis transmitted?
A: EBV transmission occurs predominantly through exposure to infected saliva, often as a result of kissing and less commonly, by means of sexual transmission. The incubation period, from the time of initial exposure to the onset of symptoms, is estimated at 30 to 50 days.

How should patients with infectious mononucleosis be managed?
A: On the basis of clinical experience, supportive care is recommended for patients with infectious mononucleosis. Acetaminophen or nonsteroidal antiinflammatory agents are recommended to manage fever, throat discomfort, and malaise. Adequate fluid intake and nutrition should also be encouraged. Although getting adequate rest is prudent, bed rest is unnecessary. Patients may excrete high levels of EBV in their saliva in the year after onset of infectious mononucleosis, but special precautions against transmission of EBV are not necessary, since most people are EBV seropositive. To minimize the risk of splenic rupture, patients may consider a return to contact sports after a minimum of 3 weeks after onset of symptoms or after they are afebrile, lack clinical symptoms or findings, and feel well enough to play — whichever comes first.

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New England Journal of Medicine - Vol. 362, No. 21

小朋友用ondanstron要注意什麼？

Does Ondansetron Mask Alternative Diagnoses in Children with Suspected Gastroenteritis?
Children who received ondansetron were more likely to return and to be admitted at the return visit but were not more likely to be given alternative diagnoses.

Does use of ondansetron in children with suspected gastroenteritis affect likelihood of admission, return visits, or alternative diagnoses? To find out, investigators conducted a retrospective chart review of 34,117 patients (age range, 3 months to 18 years) who received diagnoses of vomiting or gastroenteritis at two tertiary care pediatric emergency departments (EDs) over a 3-year period. Fifty-eight percent of patients received ondansetron.

In logistic regression analyses, patients who received ondansetron were significantly less likely than those who did not receive ondansetron to be admitted on the initial visit (odds ratio, 0.47) but were significantly more likely to return within 72 hours (OR, 1.45) and to be admitted on the return visit (OR, 1.74). Overall, patients who received ondansetron were significantly less likely to be admitted during the initial or return visit (5.3% vs. 7.3%). Of 443 patients who returned and were admitted, 76 (17%) received alternative diagnoses, most often appendicitis (16 patients), intussusception (10), bacteremia (8), and pyelonephritis (7). The likelihood of an alternative diagnosis was not associated with ondansetron use but was significantly associated with documented abdominal pain on the initial visit.

Comment: This large study provides convincing evidence that ondansetron does not usually mask alternative diagnoses in children with suspected gastroenteritis. Therefore, physicians should feel comfortable using this effective antiemetic but continue to consider etiologies of vomiting other than gastroenteritis and provide clear instructions regarding when to return to the ED.

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Katherine Bakes, MD
Published in Journal Watch Emergency Medicine May 21, 2010

Citation(s): Sturm JJ et al. Ondansetron use in the pediatric emergency department and effects on hospitalization and return rates: Are we masking alternative diagnoses? Ann Emerg Med 2010 May; 55:415.

血糖控制太快也可能出問題...

Treatment-Induced Diabetic Neuropathy
An unusual complication of rapid intensive glycemic control

In sporadic case reports — some published more than 50 years ago — clinicians have described acute severe painful neuropathy that can occur during intensive treatment of patients with poorly controlled diabetes. Researchers now describe 16 patients with this condition who were referred to a Boston diabetic neuropathy clinic.

Each patient developed severe neuropathic pain within 8 weeks of initiating intensive glycemic control. Nine patients (age range, 19–29) had type 1 diabetes, and 7 patients (age range, 31–58) had type 2 diabetes. Other common causes of neuropathy were ruled out. Average glycosylated hemoglobin levels were about 14% before intensive glycemic control and about 7% afterward. Pain was in a stocking-glove distribution in 13 patients and was diffuse in 3 patients. Autonomic symptoms (e.g., orthostatic hypotension, gastrointestinal dysfunction) occurred commonly, and standardized tests of sympathetic and parasympathetic function were abnormal in most patients. Retinopathy also worsened during the first 6 months of sustained glycemic control. Pain subsided eventually in most patients, but only after 1 to 2 years of combination drug therapies for neuropathic pain.

Comment:

In this case series — the largest to date — researchers make a convincing case for the existence of what they call "treatment-induced diabetic neuropathy." I have seen several such patients, but until now I was unaware of this syndrome. The pathophysiology and incidence of this clinical entity are unclear. However, the parallel worsening of neuropathy and retinopathy suggests a common mechanism, and, interestingly, transient worsening of retinopathy during the first year of intensive insulin therapy has occurred previously in clinical trials.

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Allan S. Brett, MD
Published in Journal Watch General Medicine May 20, 2010

Citation(s): Gibbons CH and Freeman R. Treatment-induced diabetic neuropathy: A reversible painful autonomic neuropathy. Ann Neurol 2010 Apr; 67:534.

AAA Repair

Abdominal Aortic Aneurysm Repair

Randomized trials have shown that for patients with a large abdominal aortic aneurysm endovascular repair offers a perioperative survival benefit over open repair. However, this advantage is not sustained beyond 2 years after surgery. There is concern that endovascular repair lacks durability, which may lead to an increased risk of late rupture, and that more reinterventions are required in patients undergoing this technique.

How does survival differ among patients who were treated with endovascular and open repair of abdominal aortic aneurysm?
Six years after randomization, the cumulative overall survival rates were 69.9% for open repair and 68.9% for endovascular repair, for a difference of 1.0 percentage point (95% confidence interval, −8.8 to 10.8; P=0.97). The increased perioperative mortality after open repair was counterbalanced by a larger number of deaths after discharge following endovascular repair.

What were the most common complications after repair of abdominal aortic aneurysms?
A: For open repair, the most frequent secondary intervention was correction of an abdominal incisional hernia, whereas endovascular-repair interventions were most often performed because of endograft-related complications such as endoleak and endograft migration.

What were the most common causes of death among patients who had undergone an abdominal aortic aneurysm repair?
A: The most common causes of death were cardiovascular causes (myocardial infarction, cardiac arrest, congestive heart failure, stroke and ruptured aneurysm), cancer, and pulmonary causes.

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http://content.nejm.org/cgi/content/abstract/362/20/1881