Study design: Randomized, open-label (unblinded) phase 3 study.
Setting: 151 centers, 22 countries in Asia, Europe, South and North America.
Synopsis: 682 patients with untreated multiple myeloma, who were ineligible for high-dose chemotherapy and stem cell transplant, were treated with bortezomib in combination with standard melphalan and prednisone, or melphalan and prednisone alone. The bortezomib group had improved partial or complete response (71% vs. 35%; NNT=3; p<0.001), increased median time to progression of disease (19.9 months vs. 13.1 months), and improved overall survival (87% vs. 78% over a 16-month median follow up; NNT=11; p=0.008). There were increased grade 3 adverse effects with the intervention, but no increase in grade 4 events or treatment related deaths compared to control. Limitations of the study include lack of blinding and involvement of the pharmaceutical company in data collection analysis, writing and editing of the manuscript.
Bottom line: Bortezomib is a valuable adjunct to standard treatment of multiple myeloma in patients over the age of 65 who may be ineligible for high-dose chemotherapy and stem cell transplant.
Citation: San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for the initial treatment of multiple myeloma. NEJM. 2008;359:906-917.
Does the occurrence of a shock increase the risk of death in cardiomyopathy patients with defibrillators?
Background: The SCD-HeFT trial, originally published in 2005, was instrumental in demonstrating the utility of defibrillators in the primary prevention of sudden cardiac deaths in patients with either ischemic or non-ischemic cardiomyopathy, NYHA class II or III, ejection fraction <35%, and no history of sustained ventricular tachycardia or fibrillation. This study re-examined the data derived from the SCD-HeFT trial to better understand the long-term prognosis of these patients with defibrillators who receive either appropriate shocks (ventricular fibrillation, sustained ventricular tachycardia), inappropriate shocks, or no shocks. Inappropriate shocks were defined as defibrillations due to supraventricular tachycardia, oversensing P or T waves as R waves, double counting of R waves, and artifact.
Study design: Retrospective cohort (analysis of patients randomized to implantable cardioverter-defibrillator (ICD) group in SCD-HeFT).
Setting: Multicenter trial.
Synopsis: The analysis demonstrated patients who received shocks were 11 times more likely to die compared with those who had no defibrillations (Hazard Ratio [HR]=11.3, p<0.001). These shocked patients were at more risk (HR=5.7, p<0.001) than those with inappropriate shocks (HR=2.0, p=0.002). Therefore, even inappropriate shocks themselves doubled the risk of death. Patients who received more than one shock, either appropriate or not, were at even higher odds of death (HR=8.3, p<0.001). The results highlight the higher mortality risk when patients with ICDs have received a shock (appropriate or inappropriate) and the need for further therapies to modify outcome in these patients.
Bottom Line: Appropriate or inappropriate defibrillations are associated with a poorer prognosis in patients with cardiomyopathy.
Citation: Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med. 2008(359):1009-1017.
Can a simple physical exam tool assess the degree of dehydration in children?
Background: Despite the frequency and the associated cost of acute gastroenteritis (AGE) in the pediatric population, there is no unified scale to assess the severity of dehydration. The authors of this paper previously reported a clinical dehydration scale (CDS) and applied it prospectively in a new cohort of patients ages 1 month to 5 years.
Study design: Prospective, observational study.
Setting: Single, tertiary care emergency department (ED) in Canada.
Synopsis: The CDS score is based purely on the physical findings of the child, including a) general appearance, b) eyes, c) mucous membranes, and d) amount of tears. On a point system, the patient is placed in one of three categories: no dehydration, some dehydration, moderate/severe dehydration. The trial enrolled 205 children and the CDS was applied by the triaging nurse. The attending ED pediatricians were blinded from this assessment. The CDS was able to predict the length of stay (mean + SD: no dehyrdation 245 + 181 mins; some dehydration, 397 + 302 mins; mod/severe dehydration, 501 + 389 mins), need for intravenous rehydration (none, 15%; some, 49%; mod/severe, 80%), and frequency of emesis/diarrhea as reported by the parents (none, 8.4 + 7.7; some, 13 + 10.7; mod/severe, 30.2 + 14.8). Only five children were categorized in the moderate/severe dehydration category, which may limit the ability to generalize the scoring system to that group of patients.