A modified integrated genetic model for risk prediction in younger patients with acute myeloid leukemia

Background: Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. Methods and Findings: We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0.919). Conclusions: The IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy

Should patients with hip joint prosthesis receive antibiotic prophylaxis before dental treatment?

The safety committee of the American Academy of Orthopedic Surgeons (AAOS) recommended in 2009 that clinicians should consider antibiotic prophylaxis for all patients with total joint replacement before any invasive procedure that may cause bacteremia. This has aroused confusion and anger among dentists asking for the evidence. The present review deals with different aspects of the rationale for this recommendation giving attention to views both in favor of and against it

A systematic review of the economic evidence for interventions for family carers of stroke patients

OBJECTIVES: To examine the economic evidence for interventions aimed at family carers of stroke patients. DATA SOURCES: Searches (limited to those published in English since 1990) were performed in key databases along with hand searches of relevant papers. REVIEW METHODS: Papers were restricted to studies including any economic data (broadly defined) for any intervention targeting carers explicitly or explicitly referring to a carer element, beyond involving carers in the care or intervention for patients (i.e. more than just carers being invited to observe an intervention targeted at the patient). Two reviewers independently screened full papers and extracted data using guidance from the National Institute for Health and Care Excellence, and quality assessment using the Newcastle-Ottawa Quality Assessment Scale (cohort studies), the Delphi list (randomised controlled trials) and guidelines on economic quality from the British Medical Journal. Data were reviewed descriptively as meta analyses were inappropriate due to non-comparability of studies. RESULTS: Ten papers were included in the review. These were heterogeneous in their design, intervention and economic analyses making comparison difficult. Only three of the ten papers included economic evaluations. All three reported that the intervention was less costly and had better or equivalent outcomes than the control comparator although two of these were based on the same intervention using the same dataset. CONCLUSION: There is some limited evidence that interventions for family carers of stroke patients are effective and cost effective. However, due to variation in the types of interventions examined, little can be concluded regarding implications for clinical practice