The Red Cross Red Crescent Health Information System (RCHIS): an electronic medical records and health information management system for the red cross red crescent emergency response units.

BACKGROUND: The Red Cross and Red Crescent Movement (RCRC) utilizes specialized Emergency Response Units (ERUs) for international disaster response. However, data collection and reporting within ERUs have been time-consuming and paper-based. The Red Cross Red Crescent Health Information System (RCHIS) was developed to improve clinical documentation and reporting, ensuring accuracy and ease of use while increasing compliance with reporting standards. CASE PRESENTATION: RCHIS is an Electronic Medical Record (EMR) and Health Information System (HIS) designed for RCRC ERUs. It can be accessed on Android tablets or Windows laptops, both online and offline. The system securely stores data on Microsoft Azure cloud, with synchronization facilitated through a local ERU server. The functional architecture covers all clinical functions of ERU clinics and hospitals, incorporating user-friendly features. A pilot study was conducted with the Portuguese Red Cross (PRC) during a large-scale event. Thirteen super users were trained and subsequently trained the staff. During the four-day pilot, 77 user accounts were created, and 243 patient files were documented. Feedback indicated that RCHIS was easy to use, requiring minimal training time, and had sufficient training for full utilization. Real-time reporting facilitated coordination with the civil defense authority. CONCLUSIONS: The development and pilot use of RCHIS demonstrated its feasibility and efficacy within RCRC ERUs. The system addressed the need for an EMR and HIS solution, enabling comprehensive clinical documentation and supporting administrative reporting functions. The pilot study validated the training of trainers' approach and paved the way for further domestic use of RCHIS. RCHIS has the potential to improve patient safety, quality of care, and reporting efficiency within ERUs. Automated reporting reduces the burden on ERU leadership, while electronic compilation enhances record completeness and correctness. Ongoing feedback collection and feature development continue to enhance RCHIS's functionality. Further trainings took place in 2023 and preparations for international deployments are under way. RCHIS represents a significant step toward improved emergency medical care and coordination within the RCRC and has implications for similar systems in other Emergency Medical Teams.

Guilt, shame and negative emotion in undergraduate medical education: is there a role for Balint groups?

Balint groups are a structured discussion which explores non-clinical aspects of the doctor-patient relationship. In this commentary piece we describe our experience of a Balint group for final-year medical students in a large regional hospital. We discuss that our participants reported a significant burden of negative emotion, primarily guilt and shame, in attempting to navigate the hospital environment as learners. We note how our participants perceived they would acquire the ability to manage these negative emotions simply by becoming doctors, despite being only a few months from qualification. A cultural shift in undergraduate training, combined with a challenging period for the medical profession in general, may leave new doctors isolated in the face of the emotional strain of medicine. We therefore encourage educators to consider using Balint groups as an adjunct to more traditional clinical training.

International Emergency Medical Teams Training Workshop Special Report.

The World Health Organization's (WHO; Geneva, Switzerland) Emergency Medical Team (EMT) Initiative created guidelines which define the basic procedures to be followed by personnel and teams, as well as the critical points to discuss before deploying a field hospital. However, to date, there is no formal standardized training program established for EMTs before deployment. Recognizing that the World Association of Disaster and Emergency Medicine (WADEM; Madison, Wisconsin USA) Congress brings together a diverse group of key stakeholders, a pre-Congress workshop was organized to seek out collective expertise and to identify key EMT training competencies for the future development of training programs and protocols. The future of EMT training should include standardization of curriculum and the recognition or accreditation of selected training programs. The outputs of this pre-WADEM Congress workshop provide an initial contribution to the EMT Training Working Group, as this group works on mapping training, competencies, and curriculum. Common EMT training themes that were identified as fundamental during the pre-Congress workshop include: the ability to adapt one's professional skills to low-resource settings; context-specific training, including the ability to serve the needs of the affected population in natural disasters; training together as a multi-disciplinary EMT prior to deployment; and the value of simulation in training. AlbinaA, ArcherL, BoivinM, CranmerH, JohnsonK, KrishnarajG, ManeshiA, OddyL, Redwood-CampbellL, RussellR. International Emergency Medical Teams training workshop special report. Prehosp Disaster Med. 2018;33(3):335-338.

Optimal management of malignant pleural effusions (results of CALGB 30102).

The optimal strategy to achieve palliation of malignant pleural effusions (MPEs) is unknown. This multi-institutional, prospective, randomized trial compares 2 established methods for controlling symptomatic unilateral MPEs. Patients with unilateral MPEs were randomized to either daily tunneled catheter drainage (TCD) or bedside talc pleurodesis (TP). This trial is patterned after a previous randomized trial that showed that bedside TP was equivalent to thoracoscopic TP (CALGB 9334). The primary end point of the current study was combined success: consistent/reliable drainage/pleurodesis, lung expansion, and 30-day survival. A secondary end point, survival with effusion control, was added retrospectively. This trial randomized 57 patients who were similar in terms of age (62 years), active chemotherapy (28%), and histologic diagnosis (lung, 63%; breast, 12%; other/unknown cancers, 25%) to either bedside TP or TCD. Combined success was higher with TCD (62%) than with TP (46%; odds ratio, 5.0; P = .064). Multivariate regression analysis revealed that patients treated with TCD had better 30-day activity without dyspnea scores (8.7 vs. 5.9; P = .036), especially in the subgroup with impaired expansion (9.1 vs. 4.6; P = .042). Patients who underwent TCD had better survival with effusion control at 30 days compared with those who underwent TP (82% vs. 52%, respectively; P = .024). In this prospective randomized trial, TCD achieved superior palliation of unilateral MPEs than TP, particularly in patients with trapped lungs.

Impact of age, comorbidity and symptoms on physical function in long-term breast cancer survivors (CALGB 70803).

PURPOSE: The purpose of this study was to assess the impact of aging, comorbidities and symptoms on physical function in patients surviving 20 years since adjuvant treatment for breast cancer. PATIENTS #ENTITYSTARTX00026; METHODS: Patients were originally treated on CALGB 7581 (from 1975-1980), a randomized trial of three adjuvant therapies and reassessed (153 of 193 eligible survivors) 20 years from the onset of therapy for physical function and symptoms by the EORTC QLQ-C30 and comorbidities by the OARS questionnaire. RESULTS: The average age at reassessment was 64.5 years. 66% of patients had at least two comorbidities and 22% had four or more, but relatively little interference with activities. Older patients had greater multimorbidity. Physical function was generally high and comparable to matched population norms. Older patients had greater difficulty with strenuous activities. For every increase in number of comorbidities, physical function score decreased by 5.1 (p<.001). Symptoms were also frequent (80%) and correlated strongly with decreases in function (0-100u scale) (p <.001), to an even greater degree than comorbidities. CONCLUSION: Very long-term cancer survivors have changes in physical function and symptoms largely consistent with their aging suggesting that the impact of cancer and its treatment is attenuated over time and largely replaced by the impact of age-related comorbidities and functional decline.

Patient advocates' role in clinical trials: perspectives from Cancer and Leukemia Group B investigators and advocates.

BACKGROUND: Patient advocates are increasingly involved in cooperative group trials, single-institution cancer programs, and peer-review of research applications. The purpose of this study was to evaluate the role and value of patient advocates from the perspective of Cancer and Leukemia Group B (CALGB) advocates and investigators. METHODS: An online survey was sent to current and past (within 5 years) patient advocates and investigators. RESULTS.: Response rates were 72.7% (16 of 22) for advocates and 56.4% (102 of 181) for investigators. Patient advocates were more likely than investigators to report the following: the clinical trial process benefited from advocate involvement on committees (100% of advocates vs 72.1% of investigators; P < .05), advocates contribute to protocol development (92.8% vs 33.8%, respectively; P < .001), the cultural appropriateness of protocols (21.4% vs 10.4%, respectively; P < .05), advocates assist with patient accrual (78.6% vs 23.4%, respectively; P < .001), and advocates add value to concept development and protocol review (100% vs 63.2%, respectively; P < .001). Over half of advocates and investigators reported gaps in patient advocate knowledge and suggested that additional clinical trials training was needed. To improve clinical trials, advocates suggested their earlier involvement in protocol development and increased support from investigators. CALGB investigators recommended improving patient advocate selection and communication skills training: CONCLUSIONS: The majority of patient advocates and investigators perceived benefits from advocate involvement in the clinical trials process; patient advocates placed more value on their role than investigators. The current results indicated that strategies to improve advocacy training and advocate-investigator communication may further enhance the role of patient advocates, and future studies that clarify the role of advocates in the prioritization and development of protocol, consent, and education materials, and on patient accrual, are warranted.

Does health-related quality of life improve for advanced pancreatic cancer patients who respond to gemcitabine? Analysis of a randomized phase III trial of the cancer and leukemia group B (CALGB 80303).

CONTEXT: Gemcitabine for advanced pancreatic cancer (APC) is palliative and the prognosis is poor, making health-related quality of life (HRQOL) particularly important. OBJECTIVES: We evaluated HRQOL with the EuroQol (EQ-5D™) in patients with APC participating in Cancer and Leukemia Group B 80303, a multicenter, double-blind, randomized trial comparing overall survival (OS) between two treatment arms: gemcitabine with bevacizumab or gemcitabine with placebo. METHODS: A consecutive subsample of patients was invited to complete the EQ-5D surveys. Because neither clinical nor HRQOL outcomes differed based on the study arm, analyses were pooled. Changes in mean scores from baseline to eight weeks and the prognostic value of the EQ-5D were evaluated. RESULTS: Mean index scores remained stable (0.78 at baseline [n=267], 0.79 at eight weeks [n=186], P=0.34, Wilcoxon signed rank test), attributable to a modest deterioration of physical function domain scores coincident with small improvements in pain and anxiety/depression scores. A small decline in visual analogue scale scores was observed (70.7 vs. 68.2, P=0.026). HRQOL changes within chemotherapy response strata revealed stable index scores but a trend of worsened physical function among patients with disease progression compared with those with stable or improved disease. Visual analogue scale scores trended downward over time irrespective of chemotherapy response status, with a statistically meaningful deterioration in patients who progressed (68.9 vs. 64.4, P=0.029). Baseline scores from both EQ-5D scales were significant predictors of OS in Cox proportional hazard models. CONCLUSION: Response to gemcitabine treatment in APC is not associated with appreciable improvement of global HRQOL. Small improvements in pain and mood are observed despite progressive functional decline. Those who respond to gemcitabine may experience a slight slowing of functional deterioration.

Quality of life of older patients with early-stage breast cancer receiving adjuvant chemotherapy: a companion study to cancer and leukemia group B 49907.

PURPOSE: A phase III trial (Cancer and Leukemia Group B CALGB-49907) was conducted to test whether older patients with early-stage breast cancer would have equivalent relapse-free and overall survival with capecitabine compared with standard chemotherapy. The quality of life (QoL) substudy tested whether capecitabine treatment would be associated with a better QoL than standard chemotherapy. PATIENTS AND METHODS: QoL was assessed in 350 patients randomly assigned to either standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin and cyclophosphamide [AC]; n = 182) or capecitabine (n = 168). Patients were interviewed by telephone before treatment (baseline), midtreatment, within 1 month post-treatment, and at 12, 18, and 24 months postbaseline by using questionnaires from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), a breast systemic adverse effects scale (EORTC BR23), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Compared with patients who were treated with standard chemotherapy, patients who were treated with capecitabine had significantly better QoL, role function, and social function, fewer systemic adverse effects, less psychological distress, and less fatigue during and at the completion of treatment (P ≤ .005). Capecitabine treatment was associated with less nausea, vomiting, and constipation and with better appetite than standard treatment (P ≤ .004), but worse hand-foot syndrome and diarrhea (P < .005). These differences all resolved by 12 months. CONCLUSION: Standard chemotherapy was superior to capecitabine in improving relapse-free and overall survival for older women with early-stage breast cancer. Although capecitabine was associated with better QoL during treatment, QoL was similar for both groups at 1 year. The brief period of poorer QoL with standard treatment is a modest price to pay for a chance at improved survival.

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809.

BACKGROUND: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented. METHODS: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival. RESULTS: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%. CONCLUSIONS: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.

Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer.

BACKGROUND: Tamoxifen use has been associated with increased risk of thromboembolic events (TEs) in women with breast cancer and women at high risk for the disease. Factor V Leiden (FVL) is the most common inherited clotting factor mutation and also confers increased thrombosis risk. We investigated whether FVL was associated with TE risk in women with early-stage breast cancer who took adjuvant tamoxifen. METHODS: A case-control study was conducted among 34 Cancer and Leukemia Group B (CALGB) institutions. We matched each of 124 women who had experienced a documented TE while taking adjuvant tamoxifen for breast cancer (but who were not necessarily on a CALGB treatment trial) to two control subjects (women who took adjuvant tamoxifen but did not experience TE) by age at diagnosis (+/-5 years). DNA from blood was analyzed for FVL mutations. Conditional logistic regression was used to estimate odds ratios (ORs) and to evaluate other potential factors associated with TE and tamoxifen use. All P values are based on two-sided tests. RESULTS: FVL mutations were identified in 23 (18.5%) case and 12 (4.8%) control subjects (OR = 4.66, 95% confidence interval = 2.14 to 10.14, P < .001). In the multivariable model, FVL mutation was associated with TE (OR = 4.73, 95% confidence interval = 2.10 to 10.68, P < .001). Other statistically significant factors associated with TE risk were personal history of TE and smoking. CONCLUSIONS: Among women taking adjuvant tamoxifen for early-stage breast cancer, those who had a TE were nearly five times more likely to carry a FVL mutation than those who did not have a TE. Postmenopausal women should be evaluated for the FVL mutation before prescription of adjuvant tamoxifen if a positive test would alter therapeutic decision making.

Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206.

PURPOSE: Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-alpha) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-alpha versus IFN-alpha monotherapy was conducted. PATIENTS AND METHODS: Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-alpha (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-alpha monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. RESULTS: Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-alpha and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-alpha monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-alpha. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-alpha. Patients who developed HTN on bevacizumab plus IFN-alpha had a significantly improved PFS and OS versus patients without HTN. CONCLUSION: OS favored the bevacizumab plus IFN-alpha arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-alpha.

Adherence and persistence with oral adjuvant chemotherapy in older women with early-stage breast cancer in CALGB 49907: adherence companion study 60104.

PURPOSE: Patient adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure adherence among women randomly assigned to capecitabine in a preplanned substudy of a multicenter clinical trial. PATIENTS AND METHODS: Cancer and Leukemia Group B study CALGB 49907 was a randomly assigned trial comparing standard chemotherapy versus oral chemotherapy with capecitabine in patients age 65 years or older with early-stage breast cancer. We used microelectronic monitoring system (MEMS) caps on participants' capecitabine bottles to record pill bottle openings. Capecitabine was given in two divided daily doses for 14 consecutive days of a 21-day cycle for six cycles. Adherence was calculated as the number of doses taken divided by doses expected, taking into account toxicity-related dosing changes. A participant was defined as adherent if 80% or more of expected doses were recorded by MEMS. RESULTS: Overall, 161 patients were enrolled. Median age was 71 years (range, 65 to 89 years); 124 patients (83%) persisted with capecitabine to completion of planned protocol therapy. Adherence was 78% across all cycles, and adherence did not vary by cycle (P = .32). Twenty-five percent of participants took fewer than 80% of expected doses and were nonadherent. In a logistic regression model, participants with node-negative disease (P = .01) and mastectomy (P = .01) were more likely to be nonadherent. Adherence was not related to age, tumor stage, or hormone receptor status. Adherence was not significantly associated with relapse-free survival or grade 3 or 4 toxicity. CONCLUSION: Most older women with early-stage breast cancer were adherent to short-term oral chemotherapy in a randomized clinical trial. Age was not associated with adherence.

Perioperative outcomes among patients with end-stage renal disease following coronary artery bypass surgery in the USA.

BACKGROUND: Patients with end-stage renal disease (ESRD) requiring chronic haemodialysis who undergo coronary artery bypass graft surgery (CABG) are at significant risk for perioperative mortality. However, the impact of changes in ESRD patient volume and characteristics over time on operative outcomes is unclear. METHODS: Using the Nationwide Inpatient Sample database (1988-03), we evaluated rates of CABG surgery with and without concurrent valve surgery among ESRD patients and outcomes including in-hospital mortality, and length of hospital stay. Multivariate regression models were used to account for patient characteristics and potential cofounders. RESULTS: From 1988 to 2003, annual rates of CABG among ESRD patients doubled from 2.5 to 5 per 1000 patient-years. Concomitantly, patient case-mix changed to include patients with greater co-morbidities such as diabetes, hypertension and obesity (all P < 0.001). Nonetheless, among ESRD patients, in-hospital mortality rates declined nearly 6-fold from over 31% to 5.4% (versus 4.7% to 1.8% among non-ESRD), and the median length of in-hospital stay dropped in half from 25 to 13 days (versus 14 to 10 days among non-ESRD). CONCLUSIONS: Since 1988, an increasing number of patients with ESRD have been receiving CABG in the USA. Despite increasing co-morbidities, operative mortality rates and length of in-hospital stay have declined substantially. Nonetheless, mortality rates remain almost 3-fold higher compared to non-ESRD patients indicating a need for ongoing improvement.

Differences in clinical trial patient attributes and outcomes according to enrollment setting.

PURPOSE: During the last 25 years, National Cancer Institute (NCI) cooperative trial groups have extended trial networks from academic centers to include certain community and Veterans Health Administration (VHA) centers. We compared trial patients' attributes and outcomes by these enrollment settings. PATIENTS AND METHODS: Studying 2,708 patients on one of 10 cooperative group, randomized lung trials at 272 institutions, we compared patient attributes by enrollment setting (ie, academic, community, and VHA affiliates). We used adjusted Cox regression to evaluate for survival differences by setting. RESULTS: Main member institutions enrolled 44% of patients; community affiliates enrolled 44%; and VHAs enrolled 12%. Patient attributes (ie, case-mix) of age, ethnicity, sex, and performance status varied by enrollment setting. After analysis was adjusted for patient case-mix, no mortality differences by enrollment setting were noted. CONCLUSION: Although trial patients with primarily advanced-stage lung cancer from nonacademic centers were older and had worse performance statuses than those from academic centers, survival did not differ by enrollment setting after analysis accounted for patient heterogeneity. An answer for whether long-term outcomes for patients at community and VHA centers affiliated with cooperative trial groups are equivalent to those at academic centers when care is delivered through NCI trials requires additional research among patients with longer survival horizons.

Increasing healthcare resource utilization after coronary artery bypass graft surgery in the United States.

BACKGROUND: Despite declining lengths of stay, postdischarge healthcare resource utilization may be increasing because of shifts to nonacute care settings. Although changes in hospital stay after coronary artery bypass graft (CABG) surgery have been described, patterns of discharge remain unclear. Our objective was to determine patterns of discharge disposition after CABG surgery in the United States. METHODS AND RESULTS: We examined discharge disposition after CABG procedures from 1988 to 2005 using the Nationwide Inpatient Sample. Discharges with a "nonroutine" disposition defined patients discharged with continued healthcare needs. Multivariable regression models were constructed to assess trends and factors associated with nonroutine discharge. Median length of stay among 8,398,554 discharges decreased from 11 to 8 days between 1988 and 2005 (P<0.0001). There was a simultaneous increase in nonroutine discharges from 12% in 1988 to 45% in 2005 (P<0.0001), primarily comprising home healthcare and long-term facility use. Multivariable regression models showed age, female gender, comorbidities, concurrent valve surgery, and lower-volume hospitals more likely to be associated with nonroutine discharge. CONCLUSIONS: We found a significant increase in nonroutine discharges after CABG surgery across the United States from 1988 to 2005. The significant shortening of length of stay during CABG may be counterbalanced by the increased requirement for additional postoperative healthcare services. Nonacute care institutions are playing an increasingly significant role in providing CABG patients with postdischarge healthcare and should be considered in investigations of postoperative healthcare resource utilization. The impact of these changes on long-term outcomes and net resource utilization remain unknown.

Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.

AIMS: Anacetrapib is an orally active and potent inhibitor of CETP in development for the treatment of dyslipidaemia. These studies endeavoured to establish the safety, tolerability, pharmacokinetics and pharmacodynamics of rising single doses of anacetrapib, administered in fasted or fed conditions, and to preliminarily assess the effect of food, age, gender and obesity on the single-dose pharmacokinetics and pharmacodynamics of anacetrapib. METHODS: Safety, tolerability, anacetrapib concentrations and CETP activity were evaluated. RESULTS: Anacetrapib was rapidly absorbed, with peak concentrations occurring at approximately 4 h post-dose and an apparent terminal half-life ranging from approximately 9 to 62 h in the fasted state and from approximately 42 to approximately 83 h in the fed state. Plasma AUC and C(max) appeared to increase in a less than approximately dose-dependent manner in the fasted state, with an apparent plateau in absorption at higher doses. Single doses of anacetrapib markedly and dose-dependently inhibited serum CETP activity with peak effects of approximately 90% inhibition at t(max) and approximately 58% inhibition at 24 h post-dose. An E(max) model best described the plasma anacetrapib concentration vs CETP activity relationship with an EC(50) of approximately 22 nm. Food increased exposure to anacetrapib; up to approximately two-three-fold with a low-fat meal and by up to approximately six-eight fold with a high-fat meal. Anacetrapib pharmacokinetics and pharmacodynamics were similar in elderly vs young adults, women vs men, and obese vs non-obese young adults. Anacetrapib was well tolerated and was not associated with any meaningful increase in blood pressure. CONCLUSIONS: Whereas food increased exposure to anacetrapib significantly, age, gender and obese status did not meaningfully influence anacetrapib pharmacokinetics and pharmacodynamics.

Trends in cardiac surgery-associated acute renal failure in the United States: a disproportionate increase after heart transplantation.

Acute renal failure (ARF) is common after cardiac surgery and more frequent after complex cardiac surgery. While the incidence of ARF is increasing after coronary artery bypass graft (CABG) surgery, trends in other forms of cardiac surgery remain unclear. We investigated the trend of ARF in various cardiac procedures and compared patterns using CABG surgery as a reference group. The study population consisted of discharges from the Nationwide Inpatient Sample from 1988 to 2003, grouped according to surgery as: CABG, CABG with mitral valve, CABG with other valve, valve alone, and heart transplant. Standard diagnostic codes were used to identify ARF among discharges. Multivariable regression was used to determine trends in ARF among various procedures with CABG as a reference group. The incidence of ARF increased in all five groups (p < 0.001) over the 16-year period. The ARF incidence was highest in the heart transplant group (17%). Compared to the CABG population, patients following heart transplantation developed ARF at higher rates during the study period. In contrast, while ARF increased over time in other groups, the rates of rise were slower than in CABG patients. Among heart surgery procedures, ARF incidence is highest in heart transplantation. The incidence of ARF is also increasing at a faster rate in this group of patients in contrast to other procedure groups when compared to CABG surgery. The disproportionate increase in ARF burden after heart transplantation is a concern due to its strong association with chronic kidney disease and mortality.

Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer.

PURPOSE: To explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer. PATIENTS AND METHODS: Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had prostate cancer that had progressed during androgen deprivation therapy and did not receive prior treatment with chemotherapy, immunotherapy, or other nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from randomization/registration were performed to minimize lead time bias. The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS. In addition, biochemical progression using the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS. RESULTS: The median survival time among men who experienced progression at 3 months was 9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001). Compared with men who did not progress at 3 and at 6 months, the adjusted hazard ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to 2.4; P < .001) for men who experienced progression at 3 and 6 months, respectively. In addition, biochemical progression at 3 months predicted OS. The association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32). CONCLUSION: PFS at 3 and 6 months and biochemical progression at 3 months predict OS. These observations require prospective validation.

Reproducibility of random periareolar fine needle aspiration in a multi-institutional Cancer and Leukemia Group B (CALGB) cross-sectional study.

BACKGROUND: Random periareolar fine needle aspiration (RPFNA) is a research technique developed to assess short-term breast cancer risk in women at increased risk of breast cancer. Although there is increasing acceptance of RPFNA, neither the reproducibility nor the inter-institutional compatibility of RPFNA has been established. To address these key limitations, the Cancer and Leukemia Group B (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi-institutional cross-sectional study. METHODS: Sixty-three high-risk women from five CALGB institutions (Duke, Ohio State, Roswell Park, Dana Farber, and Vermont) underwent RPFNA from July 1, 2007 to June 30, 2008. Duplicate bilateral RPFNA was performed on each woman by a single investigator on a single day. Masood Cytology Index score was assessed by a single blinded cytopathologist. RESULTS: There was a high degree of statistical agreement in the Masood Cytology Index scores of duplicate RPFNA samples from the same breast, with a Spearman correlation coefficient of 0.8312 (P < 0.0001). Importantly, although there was agreement in duplicate samples from the same breast, there was lack of agreement between duplicate samples from the opposite breast. CONCLUSIONS: This multi-institutional study shows that RPFNA is a highly reproducible measure of breast cytology in a cooperative group cross-sectional trial. RPFNA did not show a high degree of agreement between breasts, suggesting that breast cancer risk and progression may occur at different rates in individual breasts from a single woman. These studies provide proof-of-principle for future RPFNA-based cooperative group prevention studies.

Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206.

PURPOSE: Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted. PATIENTS AND METHODS: Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%). CONCLUSION: Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.