Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-ascending study of sirukumab in cutaneous or systemic lupus erythematosus.

OBJECTIVE: We undertook a 2-part, phase I, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetics of multiple intravenous infusions of sirukumab, a human anti-interleukin-6 monoclonal antibody, in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE). METHODS: In part A, patients with histologically confirmed CLE were randomized to 4 infusions of placebo or 1, 4, or 10 mg/kg sirukumab every 2 weeks. In part B, SLE patients diagnosed according to American College of Rheumatology criteria with a score of 5-12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index were randomized to 4 infusions of placebo or 10 mg/kg sirukumab every 2 weeks. RESULTS: We treated 31 CLE patients (23 with sirukumab, 8 with placebo) and 15 SLE patients (10 with sirukumab, 5 with placebo). Adverse events (AEs) occurred more often with sirukumab than placebo in CLE patients (91% versus 63%) and in SLE patients (90% versus 80%). Sirukumab led to sustained, dose-independent decreases in white blood cell counts, absolute neutrophil counts (neutropenia), and platelet counts (thrombocytopenia) and to minor elevations in total cholesterol levels. The majority of infections were mild respiratory infections. which were reported similarly across CLE cohorts but more often in sirukumab-treated than in placebo-treated SLE patients. Two serious AEs of infection occurred (pneumonia in the 10 mg/kg-treated group and iatrogenic wound infection in the 4 mg/kg-treated group). Sirukumab showed linear pharmacokinetics in CLE patients. Systemic exposure and half-life were comparable between CLE and SLE patients. No patient developed antibodies to sirukumab through 22 weeks. C-reactive protein and serum amyloid A mean concentrations were suppressed with sirukumab from week 1 to week 14. CONCLUSION: Treatment with intravenous sirukumab infusions was generally well tolerated in both CLE and SLE patients with mild, stable, active disease. Sirukumab demonstrated linear pharmacokinetics over the dose range studied and comparable systemic exposure and half-life in CLE and SLE patients.

Pain questionnaire performance in advanced prostate cancer: comparative results from two international clinical trials.

PURPOSE: To compare pain assessment questionnaires commonly used in advanced prostate cancer trials and to determine the psychometric characteristics and longitudinal relationships by contrasting questionnaire data from two international phase 2 trials. METHODS: Scores from the Present Pain Intensity (PPI) question of the McGill Pain Questionnaire, the pain intensity scale of the Brief Pain Inventory (BPI), and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) were analyzed using Pearson correlation, intraclass correlation coefficient, and Cronbach's α, respectively. Concordance was evaluated with Cohen's kappa coefficient and McNemar test at baseline (n = 224) and two subsequent observations. RESULTS: PPI and FACT-P scores were associated with the BPI score at baseline for Trials 1 and 2: PPI r = 0.66 and 0.80, respectively (P < 0.001); FACT-P (pain scale) r = -0.76 and -0.82, respectively (P < 0.001). However, concordance analysis revealed that the BPI identified pain (score > 0) at higher rates than the PPI: at baseline, BPI: 89 % (64/72) and 77 % (95/124), PPI: 68 % (49/72) and 64 % (79/124) [Trials 1 and 2, respectively; McNemar test (P < 0.001) for both studies]. The FACT-P pain scale identified pain similarly to the BPI pain intensity scale; longitudinal analysis produced comparable findings. All pain scales met standard psychometric acceptability criteria, but the BPI and FACT-P performed better than the PPI. CONCLUSIONS: Data suggest the BPI pain intensity and FACT-P pain scales are better than the PPI question at capturing the pain experience among patients with advanced prostate cancer. Additional comparative research is needed in larger population samples.

Health-related quality of life among patients with metastatic melanoma: results from an international phase 2 multicenter study.

Clinical and health-related quality of life (HRQoL) information was analyzed to determine: (a) patient-reported signs, symptoms, and functioning, (b) HRQoL questionnaire psychometrics, and (c) treatment impact on HRQoL. Data from the Melanoma Subscale (MS) of the Functional Assessment of Cancer Therapy-Melanoma and the worst pain question from the Brief Pain Inventory (BPI) were taken from a clinical trial evaluating intetumumab alone or with dacarbazine in Stage IV metastatic melanoma. Descriptive statistics examined patient-reported disease burden at baseline. Correlations explored clinical endpoint and HRQoL associations. Psychometrics included Cronbach's α internal consistency and intraclass correlation coefficient (ICC). Treatment impact on HRQoL was evaluated through HRQoL maintenance and response analyses. Patients (n=127) had a mean age of 62 years, a mean±SD hemoglobin of 13.0±2.6 g/dl, and a mean±SD lactic dehydrogenase of 394±454 IU/l. Ninety-eight percent were Caucasian, 67% were men, and 64% had an Eastern Cooperative Oncology Group status of 0. Baseline BPI worst pain and MS scores (mean±SD) were 1.6±2.2 and 54.5±7.2, respectively. Top three patient-reported health decrements in the MS were appetite, fatigue, and limited physical activity. Observed HRQoL decrements were consistent with the literature. MS and BPI worst pain item demonstrated good psychometrics: Cronbach's α and ICC for the MS were 0.79 and 0.86, respectively; BPI ICC was 0.74. A trend for HRQoL response was observed 3 weeks postbaseline in the dacarbazine + 10 mg/kg intetumumab arm compared with dacarbazine + placebo: 22 versus 10%, respectively, for the MS; 23 versus 5% for the BPI. Further research on the HRQoL benefit of intetumumab in larger studies appears warranted.

Collaboration between civilian and military healthcare professionals: a better way for planning, preparing, and responding to all hazard domestic events.

Collaboration is used by the US National Security Council as a means to integrate inter-federal government agencies during planning and execution of common goals towards unified, national security. The concept of collaboration has benefits in the healthcare system by building trust, sharing resources, and reducing costs. The current terrorist threats have made collaborative medical training between military and civilian agencies crucial. This review summarizes the long and rich history of collaboration between civilians and the military in various countries and provides support for the continuation and improvement of collaborative efforts. Through collaboration, advances in the treatment of injuries have been realized, deaths have been reduced, and significant strides in the betterment of the Emergency Medical System have been achieved. This review promotes collaborative medical training between military and civilian medical professionals and provides recommendations for the future based on medical collaboration.

Measuring team performance in simulation-based training: adopting best practices for healthcare.

Team performance measurement is a critical and frequently overlooked component of an effective simulation-based training system designed to build teamwork competencies. Quality team performance measurement is essential for systematically diagnosing team performance and subsequently making decisions concerning feedback and remediation. However, the complexities of team performance pose a challenge to effectively measuring team performance. This article synthesizes the scientific literature on this topic and provides a set of best practices for designing and implementing team performance measurement systems in simulation-based training.

Debriefing medical teams: 12 evidence-based best practices and tips.

BACKGROUND: Medical teams are commonly called on to perform complex tasks, and when those tasks involve saving the lives of critically injured patients, it is imperative that teams perform optimally. Yet, medical care settings do not always lend themselves to efficient teamwork. The human factors and occupational sciences literatures concerning the optimization of team performance suggest the usefulness of a debriefing process--either for critical incidents or recurring events. Although the debrief meeting is often used in the context of training medical teams, it is also useful as a continuous learning tool throughout the life of the team. WHAT ARE GOOD DEBRIEFS? AN OVERVIEW: The debriefing process allows individuals to discuss individual and team-level performance, identify errors made, and develop a plan to improve their next performance. BEST PRACTICES AND TIPS FOR DEBRIEFING TEAMS: THE DEBRIEF PROCESS: The list of 12 best practices and tips--4 for hospital leaders and the remainder for debrief facilitators or team leaders--should be useful for teams performing in various high-risk areas, including operating rooms, intensive care units, and emergency departments. The best practices and tips should help teams to identify weak areas of teamwork and develop new strategies to improve teamwork competencies. Moreover, they include practices that support both regular, recurring debriefs and critical-incident debriefings. Team members should follow these main guidelines--also provided in checklist form--which include ensuring that the organization creates a supportive learning environment for debriefs (concentrating on a few critical performance issues), providing feedback to all team members, and recording conclusions made and goals set during the debrief to facilitate future feedback.

The prognostic significance of patient-reported outcomes in pancreatic cancer cachexia.

Data from a clinical study of 86 pancreatic cancer patients with involuntary, significant weight loss (cachexia) were used to explore the relationship between patient-reported outcomes (PROs) and survival. In all, 28 pancreatic cancer patients with cachexia were given gemcitabine (Gemzar) plus 3 mg/kg of infliximab (Remicade), 28 were given gemcitabine plus 5 mg/kg of infliximab, and 30 were given gemcitabine plus placebo in a double-blinded, phase II, multicenter trial. PRO endpoints included scores from the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Functional Assessment of Anorexia/ Cachexia Therapy (FAACT), Brief Pain Inventory (BPI), and the Short-Form 36 general health survey (SF-36). Population mean scores at baseline indicated fatigue problems (FACIT-F), nutritional health issues (FAACT), and mild-to-moderate pain (BPI "worst pain" score). Baseline normalized SF-36 values for physical functioning, vitality, and mental health indicated substantial impairment. Baseline fatigue and physical-functioning scores predicted survival as well as, or better than, baseline Karnofsky Performance Status or hemoglobin level. A cut-point in the FACIT-F score (median < or = 30) strongly predicted mortality; patients with greater fatigue had a lower median overall survival than did those with less fatigue. These findings supported several features of an a priori clinical-benefit model. Patient-reported fatigue provided powerful prognostic information; tracking of this symptom may be useful for treatment planning and medical monitoring of advanced-stage pancreatic cancer patients with cachexia. These results must be confirmed by larger trials.