In network meta-analyses, several treatments can be compared by connecting evidence from clinical trials that have investigated two or more treatments. The resulting trial network allows estimating the relative effects of all pairs of treatments taking indirect evidence into account. For a valid analysis of the network, consistent information from different pathways is assumed. Consistency can be checked by contrasting effect estimates from direct comparisons with the evidence of the remaining network. Unfortunately, one deviating direct comparison may have side effects on the network estimates of others, thus producing hot spots of inconsistency.

Background The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors. Methods and Results The short-term effects of 8.4 to 10.5 μg of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4±1.3 versus 6.4±1.1 mm Hg; P <0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8±1.4 versus 9.4±1.3 mm Hg; P <0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects. Conclusions Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.

Case management by health care assistants in small primary care practices provides unclear benefit for improving depression symptoms. To determine whether case management provided by health care assistants in small primary care practices is more effective than usual care in improving depression symptoms and process of care for patients with major depression. Cluster randomized, controlled trial. A central automated system generated the randomization scheme, which was stratified by urban and rural practices; allocation sequence was concealed until groups were assigned. 74 small primary care practices in Germany from April 2005 to September 2007. 626 patients age 18 to 80 years with major depression. Structured telephone interview to monitor depression symptoms and support for adherence to medication, with feedback to the family physician. Depression symptoms at 12 months, as measured by the Patient Health Questionnaire-9 (PHQ-9); secondary outcomes were patient assessment of chronic illness care, adherence to medication, and quality of life. A total of 310 patients were randomly assigned to case management and 316 to usual care. At 12 months, 249 intervention recipients and 278 control patients were assessed; 555 patients were included in a modified intention-to-treat-analysis (267 intervention recipients vs. 288 control patients). Compared with control patients, intervention recipients had lower mean PHQ-9 values in depression symptoms (−1.41 [95% CI, −2.49 to −0.33]; P = 0.014), more favorable assessments of care (3.41 vs. 3.11; P = 0.011), and increased treatment adherence (2.70 vs. 2.53; P = 0.042). Quality-of-life scores did not differ between groups. Patients, health care assistants, family physicians, and researchers were not blinded to group assignment, and 12-month follow-up of patients was incomplete. Case management provided by primary care practice–based health care assistants may reduce depression symptoms and improve process of care for patients with major depression more than usual care. German Ministry of Education and Research.