How we treat paroxysmal nocturnal hemoglobinuria: A consensus statement of the Canadian PNH Network and review of the national registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by intravascular hemolysis, thrombophilia, and marrow failure. Its phenotype is due to absent or reduced expression of GPI-linked complement regulators and subsequent sensitivity of hematopoietic cells to complement-mediated damage and lysis. Introduction of the terminal complement inhibitor eculizumab drastically improved outcomes in PNH patients; however, despite this improvement, there remain several challenges faced by PNH patients and physicians who care for them. One of the most important is increasing awareness of the heterogeneity with which patients can present, which can lead to significant delays in recognition. Data from the Canadian PNH Registry are presented to demonstrate the variety of presenting symptoms. In Canada, geography precludes consolidation of care to just a few centers, so management is distributed across academic hospitals, linked together as the Canadian PNH Network. The Network over the last several years has developed educational programs and clinical checklists and has worked to standardize access to diagnostics across the country. Herein, we address some of the common diagnostic and therapeutic challenges faced by PNH physicians and give our recommendations. Gaps in knowledge are also addressed, and where appropriate, consensus opinion is provided.

Use of prothrombin complex concentrate in warfarin anticoagulation reversal in the emergency department: a quality improvement study of administration delays.

BACKGROUND: Quick reversal of warfarin anticoagulation is important in life threatening bleeding. The aim of this study is to improve the administration delay when using Prothrombin Complex Concentrate (PCC) for the emergent reversal of warfarin anticoagulation in the emergency department. METHODS: An audit and feedback quality improvement project was conducted in three phases: a retrospective audit phase, an analysis and feedback phase and prospective evaluation phase. The charts of all eligible patients in a single Emergency Department (ED) in Québec, Canada, who received PCC since the introduction of this product in 2009 until October 31, 2011, were retrospectively audited. The administration delay of PCC was calculated from the time of prescription to the time of administration. With the data, we determined where improvements could be attained, and jointly with all stakeholders in the ED and the blood bank, we created an action plan to ensure the timely administration of PCC. The action plan was then implemented and a six-month prospective evaluation study was conducted to determine any improvement. RESULTS: Seventy-seven charts were reviewed in the retrospective chart audit. The mean administration delay was 73.6 minutes (STD [34.1]) with a median of 70.0 minutes (25-75% IQR [45.0-95.0]). We found that this delay was principally due to the following barriers: communication problems between the ED and the blood bank as well as delivery inefficiencies. An action plan that involved a flowchart to remind all clinicians how to order PCC and a new delivery method from the blood bank to the ED were developed. During the 6 months following the implementation of our action plan, 39 patients received PCC and the mean administration time decreased to 33.2 minutes (STD [14.2])(p < .0001) with a median of 30.0 minutes (25-75% IQR [24.3-38.8]). CONCLUSION: By implementing an action plan comprising of a flowchart and a new delivery process, this audit and feedback quality improvement project reduced the administration time of PCC by more than half. Future studies to measure the impact of a similar audit and feedback process involving an action plan in other centers should be conducted before this type of quality improvement process is implemented on wider scale.

Randomized clinical trial on cognitive therapy for depression in women with metastatic breast cancer: psychological and immunological effects.

OBJECTIVE: Depression is particularly prevalent in patients with advanced cancer. Cognitive therapy (CT) is an empirically supported treatment for depression in the general population. However, efficacy remains to be demonstrated in patients with advanced cancer. A prior controlled trial of CT in a group format showed improvements in depression, mood disturbance, and self-esteem; however, these effects were not maintained over time. Studies examining the efficacy of individual format CT interventions that may ensure more long-term maintenance of benefits are necessary. This study assessed the efficacy of CT for depression administered individually in women with metastatic breast cancer and its effect on immune function. METHOD: Forty-five women were randomly assigned to either individual CT or to a waiting-list control (WLC) condition. CT was composed of eight weekly sessions of CT and three booster sessions administered at 3-week intervals following the end of treatment. RESULTS: Patients treated with CT had significantly lower scores on the Hamilton Depression Rating Scale at posttreatment compared to untreated patients. Pooled data from both groups indicated significant reductions of depressive symptoms from pre- to posttreatment, as well as reduction of associated symptoms including anxiety, fatigue, and insomnia symptoms. These effects were well sustained at the 3- and 6-month follow-up evaluations. CT for depression did not appear to have a significant impact on immune functioning. SIGNIFICANCE OF RESULTS: Findings of this study support the efficacy of CT for depression in this population and suggest that the administration of individual and booster sessions after treatment termination may be instrumental in sustaining the treatment effects over time.