The results of this trial suggest that it is safe to withhold additional diagnostic testing in patients with suspected PE, low pretest clinical probability, and a negative D-dimer test. Even in patients with moderate to high pretest clinical probability, a non-diagnostic VQ scan, and normal venous ultrasonography, only one patient with a negative D-dimer had a venous thromboembolic event at six months follow-up. The assay used for this study was an erythrocyte agglutination SimpliRED assay. Reported sensitivity is approximately 90%, and specificity is approximately 75%. To the readers, it should be noted that the authors defined a low probability Wells score as 4 rather than 1.5 or lower.
Efficacy and Safety of Inhaled Insulin Therapy in Adults with Diabetes Mellitus
Ceglia L, Lau J, Pittas AG. Meta-analysis: efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus. Ann Intern Med. 2006 Nov 7;145(9):665-675.
Despite its effectiveness in attaining glycemic control, there is considerable resistance to insulin use by patients and healthcare providers, primarily because of the need for subcutaneous injection. In January 2006, the U.S. Food and Drug Administration (FDA) approved the first formulation of inhaled insulin for clinical use in nonsmoking adults with type 1 or type 2 diabetes and no pulmonary disease. The authors of this paper present a systematic review to examine the efficacy, safety, and patient acceptability of inhaled insulin.
The authors conducted a search of MEDLINE to find English-language, randomized, controlled trials of inhaled insulin in nonpregnant adults with diabetes. To find unpublished studies, the authors reviewed the briefing document on Exubera powder for oral inhalation (Pfizer Inc., New York). An abstract was included if it reported original data from controlled trials in patients with type 1 or 2 diabetes and hemoglobin A1C outcomes for patients receiving inhaled insulin versus outcomes for a comparison group (subcutaneous insulin or oral hypoglycemics). Studies with less than 12 weeks duration were excluded because no comparison could be made regarding glycemic efficacy. For glycemic efficacy, the primary outcome was the treatment group difference in hemoglobin A1C from baseline. Secondary outcome was the proportion of patients with hemoglobin A1C levels less than 7%. To evaluate safety, the primary outcomes were severe hypoglycemia (glucose ≤36 mg/dL), cough, and treatment group difference in pulmonary function variables.
Sixteen trials involving a total of 4,023 patients met inclusion criteria. Seven trials compared inhaled insulin with various subcutaneous insulin regimens in patients with type 1 diabetes. Nine trials compared inhaled insulin with subcutaneous insulin or oral hypoglycemic agents in patients with type 2 diabetes. Inhaled insulin was given with meals and titrated according to study-specific glucose goals. Subcutaneous insulin was titrated to the same specific goals. Doses of oral hypoglycemic agents were adjusted for glycemic targets in only two of the nine trials. The combined data from the studies demonstrated a small but statistically significant decrease in the levels of baseline hemoglobin A1C levels in favor of subcutaneous insulin (weighted mean difference 0.08%, [CI 0.03% to 0.14%]) in patients with type 1 or type 2 diabetes. The greatest advantage of subcutaneous insulin was noted in the study with the longest duration (104 weeks). There was no difference between the study groups in studies with duration of 24 weeks or less. Patients with type 1 or type 2 diabetes taking inhaled insulin were no more likely to achieve hemoglobin A1C levels less than 7% than those using subcutaneous insulin.
The combined data from studies comparing inhaled insulin to oral hypoglycemic agents in patients with type 2 diabetes showed that inhaled insulin lowered hemoglobin A1C levels more effectively (weighted mean difference -1.04%, [CI -1.59% to -0.49%]). In studies in which the oral hypoglycemic agents were titrated, inhaled insulin still lowered baseline hemoglobin A1C levels but to a lesser degree (weighted mean difference -0.20%, [CI – 0.34% to -0.07%]). Patients with type 2 diabetes taking inhaled insulin were more likely to achieve hemoglobin A1C levels less than 7% than those taking oral agents.