Clinical operations of academic versus non-academic emergency departments: a descriptive comparison of two large emergency department operations surveys

BACKGROUND: Academic and non-academic emergency departments (EDs) are regularly compared in clinical operations benchmarking despite suggestion that the two groups may differ in their clinical operations characteristics. and outcomes. We sought to describe and compare clinical operations characteristics of academic versus non-academic EDs. METHODS: We performed a descriptive, comparative analysis of academic and non-academic adult and general EDs with 40,000+ annual encounters, using the Academy of Academic Administrators of Emergency Medicine (AAAEM)/Association of Academic Chairs of Emergency Medicine (AACEM) and Emergency Department Benchmarking Alliance (EDBA) survey results. We defined academic EDs as primary teaching sites for emergency medicine (EM) residencies and non-academic EDs as sites with minimal resident involvement. We constructed the academic and non-academic cohorts from the AAAEM/AACEM and EDBA surveys, respectively, and analyzed metrics common to both surveys. RESULTS: Eighty and 454 EDs met inclusion criteria for academic and non-academic EDs, respectively. Academic EDs had more median annual patient encounters (73,001 vs 54,393), lower median proportion of pediatric patients (6.3% vs 14.5%), higher median proportion of EMS patients (27% vs 19%), and were more commonly designated as Level I or II Trauma Centers (94% vs 24%). Median patient arrival-to-provider times did not differ (26 vs 25 min). Median length-of-stay was longer (277 vs 190 min) for academic EDs, and left-before-treatment-complete was higher (5.7% vs 2.9%). MRI utilization was higher for academic EDs (2.2% patients with at least one MRI vs 1.0 MRIs performed per 100 patients). Patients-per-hour of provider coverage was lower for academic EDs with and without consideration for advanced practice providers and residents. CONCLUSIONS: Demographic and operational performance measures differ between academic and non-academic EDs, suggesting that the two groups may be inappropriate operational performance comparators. Causes for the differences remain unclear but the differences appear not to be attributed solely to the academic mission

Oxaliplatin-DNA adduct formation in white blood cells of cancer patients

In this study, we investigated the kinetics of oxaliplatin-DNA adduct formation in white blood cells of cancer patients in relation to efficacy as well as oxaliplatin-associated neurotoxicity. Thirty-seven patients with various solid tumours received 130 mg m−2 oxaliplatin as a 2-h infusion. Oxaliplatin-DNA adduct levels were measured in the first cycle using adsorptive stripping voltammetry. Platinum concentrations were measured in ultrafiltrate and plasma using a validated flameless atomic absorption spectrometry method. DNA adduct levels showed a characteristic time course, but were not correlated to platinum pharmacokinetics and varied considerably among individuals. In patients showing tumour response, adduct levels after 24 and 48 h were significantly higher than in nonresponders. Oxaliplatin-induced neurotoxicity was more pronounced but was not significantly different in patients with high adduct levels. The potential of oxaliplatin-DNA adduct measurements as pharmacodynamic end point should be further investigated in future trials

Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial

Despite an improved antitumor efficacy as noticed by an enhanced response rate and an improved progression-free survival, the hepatic intra-arterial fotemustine did not increase the overall survival of uveal melanoma patients with liver metastases only. We propose to consider intrahepatic treatment as an experimental approac

DNA alkylation and interstrand cross-linking by treosulfan

The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treosulfan is required for cytotoxicity in vitro. DNA alkylation and interstrand cross-linking of plasmid DNA is observed after treosulfan treatment, but this is again produced via the epoxide species. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells, cross-links form slowly, reaching a peak at approximately 24 h. Incubation of K562 cells with preformed epoxides shows faster and more efficient DNA cross-linking. © 1999 Cancer Research Campaig

Creation of Surge Capacity by Early Discharge of Hospitalized Patients at Low Risk for Untoward Events

Objectives: US hospitals are expected to function without external aid for up to 96 hours during a disaster; however, concern exists that there is insufficient capacity in hospitals to absorb large numbers of acute casualties. The aim of the study was to determine the potential for creation of inpatient bed surge capacity from the early discharge (reverse triage) of hospital inpatients at low risk of untoward events for up to 96 hours. Methods: In a health system with 3 capacity-constrained hospitals that are representative of US facilities (academic, teaching affiliate, community), a variety (N = 50) of inpatient units were prospectively canvassed in rotation using a blocked randomized design for 19 weeks ending in February 2006. Intensive care units (ICUs), nurseries, and pediatric units were excluded. Assuming a disaster occurred on the day of enrollment, patients who did not require any (previously defined) critical intervention for 4 days were deemed suitable for early discharge. Results: Of 3491 patients, 44% did not require any critical intervention and were suitable for early discharge. Accounting for additional routine patient discharges, full use of staffed and unstaffed licensed beds, gross surge capacity was estimated at 77%, 95%, and 103% for the 3 hospitals. Factoring likely continuance of nonvictim emergency admissions, net surge capacity available for disaster victims was estimated at 66%, 71%, and 81%, respectively. Reverse triage made up the majority (50%, 55%, 59%) of surge beds. Most realized capacity was available within 24 to 48 hours. Conclusions: Hospital surge capacity for standard inpatient beds may be greater than previously believed. Reverse triage, if appropriately harnessed, can be a major contributor to surge capacity

Phase I dose escalation study of telatinib (BAY 57-9352) in patients with advanced solid tumours

Telatinib (BAY 57-9352) is an orally available, small-molecule inhibitor of vascular endothelial growth factor receptors 2 and 3 (VEGFR-2/-3) and platelet-derived growth factor receptor β tyrosine kinases. In this multicentre phase I dose escalation study, 71 patients with refractory solid tumours were enroled into 14 days on/7 days off (noncontinuous dosing) or continuous dosing groups to receive telatinib two times daily (BID). Hypertension (23%) and diarrhoea (7%) were the most frequent study drug-related adverse events of CTC grade 3. The maximum-tolerated dose was not reached up to a dose of 1500 mg BID continuous dosing. Telatinib was rapidly absorbed with median tmax of 3 hours or less. Geometric mean Cmax and AUC0−12 increased in a less than dose-proportional manner and plateaued in the 900–1500 mg BID dose range. Two renal cell carcinoma patients reached a partial response. Tumour blood flow measured by contrast-enhanced magnetic resonance imaging and sVEGFR-2 plasma levels decreased with increasing AUC0−12 of telatinib. Telatinib is safe and well tolerated up to a dose of 1500 mg BID continuous dosing. Based on pharmacokinetic and pharmacodynamic criteria, 900 mg telatinib BID continuously administered was selected as the recommended phase II dose

Rationale for combination therapy of chronic myelogenous leukaemia with imatinib and irradiation or alkylating agents: implications for pretransplant conditioning

The tyrosine kinase activity of the BCR–ABL oncoprotein results in reduced apoptosis and thus prolongs survival of chronic myelogenous leukaemia cells. The tyrosine kinase inhibitor imatinib (formerly STI571) was reported to selectively suppress the proliferation of BCR–ABL-positive cells. Assuming that imatinib could be included in pretransplantation conditioning therapies, we tested whether combinations of imatinib and γ-irradiation or alkylating agents such as busulfan or treosulfan would display synergistic activity in BCR–ABL-positive chronic myelogenous leukaemia BV173 and EM-3 cell lines. Further, primary cells of untreated chronic myelogenous leukaemia patients were assayed for colony forming ability under combination therapy with imatinib. Additionally, the cytotoxic effect of these combinations on BCR–ABL-negative cells was investigated. In the cell lines a tetrazolium based MTT assay was used to quantify growth inhibition after exposure to cytotoxic drugs alone or to combinations with imatinib. Irradiation was applied prior to exposure to imatinib. Interaction of drugs was analysed using the median-effect method of Chou and Talalay. The combination index was calculated according to the classic isobologram equation. The combination imatinib + γ-irradiation proved to be significantly synergistic over a broad range of cell growth inhibition levels in both BCR–ABL-positive cell lines and produced the strongest reduction in primary chronic myelogenous leukaemia colony-forming progenitor cells. Combinations of imatinib + busulfan and imatinib + treosulfan showed merely additive to antagonistic effects. Imatinib did not potentiate the effects of irradiation or cytotoxic agents in BCR–ABL-negative cells. Our data provide the basis to further develop imatinib-containing conditioning therapies for stem cell transplantation in chronic myelogenous leukaemia

A clinical phase II study with sorafenib in patients with progressive hormone-refractory prostate cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV

Sorafenib is a multi-kinase inhibitor with antiangiogenic and antiproliferative activity. The activity of sorafenib in progressive hormone-refractory prostate cancer (HRPC) patients was investigated in a phase II clinical study. Progressive HRPC patients received sorafenib 400 mg bid p.o. continuously. Only patients with no prior chemotherapy, and either one-unidimensional measurable lesion according to RECIST-criteria or increasing prostate-specific antigen (PSA) values reflecting a hormone-refractory situation, were eligible for study entry. The primary study objective was the rate of progression-free survival of ⩾12 weeks (PFS12). Secondary end points were overall response, overall survival, and toxicity. Fifty-seven patients with PC were enrolled. Two patients had to be withdrawn from the set of eligible patients. According to RECIST criteria, 4 patients out of 55 evaluable patients showed stable disease (SD). According to PSA–response, we saw 11 patients with SD PSA and 2 patients were responders at 12 weeks (PFS12=17/55=31%). Among the 257 adverse events, 15 were considered drug related of maximum CTC-grade 3. Twenty-four serious adverse events occurred in 14 patients (14/55=26%). Seven of them were determined to be drug related. No treatment-related death was observed. Sorafenib has antitumour activity in HRPCP when evaluated for RECIST- and PSA-based response. Further investigation as a component of combination regimens is necessary to evaluate its definite or overall clinical benefit for HRPCP

Oxaliplatin-DNA adduct formation in white blood cells of cancer patients

In this study, we investigated the kinetics of oxaliplatin-DNA adduct formation in white blood cells of cancer patients in relation to efficacy as well as oxaliplatin-associated neurotoxicity. Thirty-seven patients with various solid tumours received 130 mg m−2 oxaliplatin as a 2-h infusion. Oxaliplatin-DNA adduct levels were measured in the first cycle using adsorptive stripping voltammetry. Platinum concentrations were measured in ultrafiltrate and plasma using a validated flameless atomic absorption spectrometry method. DNA adduct levels showed a characteristic time course, but were not correlated to platinum pharmacokinetics and varied considerably among individuals. In patients showing tumour response, adduct levels after 24 and 48 h were significantly higher than in nonresponders. Oxaliplatin-induced neurotoxicity was more pronounced but was not significantly different in patients with high adduct levels. The potential of oxaliplatin-DNA adduct measurements as pharmacodynamic end point should be further investigated in future trials