Synopsis: Seventeen randomized controlled trials and three quasi-randomized controlled trials of 3,384 patients were selected for statistical analysis. Overall, corticosteroids did not improve 28-day, all-cause mortality in severe sepsis and septic shock. There was a statistically significant reduction in 28-day mortality only for the subgroup of patients receiving prolonged low-dose steroid treatment (37.5% vs. 44% in the control group).
There was no increased risk of gastrointestinal hemorrhage, superinfection, or neuromuscular weakness seen in treated patients.
The trials differed in the types of corticosteroid used, the time to institution of therapy, bolus versus continuous administration, duration of therapy, and abrupt versus gradual interruption of treatment. All of these factors make the clinical application of the data challenging.
Bottom line: Many questions remain about the optimal dose, timing, and duration of corticosteroids in patients with vasopressor-dependent sepsis and septic shock, but there appears to be a modest mortality benefit with prolonged low-dose corticosteroid therapy.
Citation: Annane D, Bellissant E, Bollaert P, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009;301(22): 2362-2375.
8) Testing for FVL Mutation but Not 20210A Predicts Recurrent VTE Risk
Clinical question: Are the rates of recurrent VTE higher in adults with VTE who possess either the factor V Leiden (FVL) or Prothrombin G20210A mutation, and what are the rates of VTE among family members?
Background: Clinicians commonly test for genetic mutations when treating patients who have a thrombotic event. However, the utility of such tests on predicting the risk for recurrent events and on outcomes needs review.
Study design: Meta-analysis.
Setting: Literature search of MEDLINE, EMBASE, the Cochrane Library, CINAHL, and PsycInfo.
Synopsis: Forty-six articles were selected for statistical analysis. The presence of either homozygous or heterozygous FVL mutation increased the risk of recurrent VTE compared with individuals without the FVL mutation (OR 2.65 and 1.56, respectively).
Compared with family members of adults without the FVL mutation, the presence of either homozygous or heterozygous FVL mutation predicts VTE in family members (OR 18 and 3.5, respectively).
The presence of G20210A is not predictive of recurrent VTE compared with individuals without this mutation. There is not sufficient evidence regarding the predictive value of the G20210A mutation on the risk of VTE in family members.
No studies directly address the effect of testing on outcomes other than recurrent VTE. In family members who were tested, there did not seem to be any impact on daily behavior, recognition of VTE risk factors, or perceived stress from testing.
Bottom line: FVL mutation increases the risk of recurrent VTE and predicts VTE in family members. The benefits of testing family members remain unclear.
Citation: Segal J, Brotman, D, Necochea, A, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301 (23):2472-2485. TH
PEDIATRIC HM LITERATURE
Lower Rates of Serious Bacterial Infection in Young Febrile Infants with Influenza
By Mark Shen, MD
Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.
Clinical question: What is the risk of serious bacterial infection (SBI) in febrile infants ≤60 days of age with influenza virus infections?
Background: Febrile infants with documented viral infections have a lower rate of SBI than febrile infants who do not have a positive test for a specific virus. The literature strongly supports this finding with respiratory syncytial virus (RSV), although the specific association with influenza is less clear, particularly as there is an increased risk of secondary bacterial infections in patients of all ages with influenza.
Study design: Secondary analysis of a prior prospective study.
Setting: Five pediatric EDs.
Synopsis: This was a secondary analysis of a prior prospective study (1998-2001) that examined the relationship between RSV infection and SBI in febrile infants ≤60 days of age. This analysis was restricted to centers in which bacterial cultures were obtained and the standard evaluation included testing for influenza. Of 844 infants tested for influenza, SBI status could be determined in 809 (95.9%), and 123 tested positive for influenza. Of those with influenza, only three (2.5%) were found to have an SBI, and all three had a urinary tract infection (UTI). By comparison, 13.3% of the influenza-negative patients had SBIs, 10.8% of which were UTIs.
The primary study limitation is the secondary nature of the analysis. The enrollment period was October through March of each year, and influenza virus peaked in December and January of each year studied. In addition, the authors were able to refer to prospectively collected data on SBI status. These data are consistent with other studies demonstrating a lower likelihood of SBI in documented viral infections.
Bottom line: Febrile infants with influenza virus infection are at lower risk of serious bacterial infection.
Citation: Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk of serious bacterial infections in young febrile infants. Pediatrics. 2009;124:30-39.