Lucinda Cassells

Rigorously Defining and Analyzing Medical Processes: An Experience Report

This paper describes our experiences in defining the processes associated with preparing and administrating chemotherapy and then using those process definitions as the basis for analyses aimed at finding and correcting defects. The work is a collaboration between medical professionals from a major regional cancer center and computer science researchers. The work uses the Little-JIL language to create precise process definitions, the Propel system to specify precise process requirements, and the FLAVERS system to verify that the process definitions adhere to the requirement specifications. The paper describes how these technologies were applied to successfully identify defects in the chemotherapy process. Although this work is still ongoing, early experiences suggest that this approach can help reduce medical errors and improve patient safety. The work has also helped us to learn about the desiderata for process definition and analysis technologies, both of which are expected to be broadly applicable to other domains.

Experience modeling and analyzing medical processes: UMass/baystate medical safety project overview

This paper provides an overview of the UMass/Baystate Medical Safety project, which has been developing and evaluating tools and technology for modeling and analyzing medical processes. We describe the tools that currently comprise the Process Improvement Environment, PIE. For each tool, we illustrate the kinds of information that it provides and discuss how that information can be used to improve the modeled process as well as provide useful information that other tools in the environment can leverage. Because the process modeling notation that we use has rigorously defined semantics and supports creating relatively detailed process models (for example, our models can specify alternative ways of dealing with exceptional behavior and concurrency), a number of powerful analysis techniques can be applied. The cost of eliciting and maintaining such a detailed model is amortized over the range of analyses that can be applied to detect errors, vulnerabilities, and inefficiencies in an existing process or in proposed process modifications before they are deployed.

Low Infectious Morbidity after Intensive Chemotherapy and Autologous Peripheral Blood Progenitor Cell Transplantation in the Outpatient Setting for Women with Breast Cancer

Autologous peripheral blood progenitor cell (PBPC) transplantation is increasingly employed in the outpatient setting, yet data on early complications following PBPC transplantation are scant. We evaluated 105 women with high-risk primary or metastatic breast cancer who were treated at a single institution during 1996--1997. The mean duration of neutropenia (absolute neutrophil count, <500 cells/mm(3)) was 7.5 days. Twenty-nine percent of women remained afebrile throughout the neutropenic period. Of the remaining 71%, most (64 of 75) had fever of unknown origin. Infections, mostly of mild severity, occurred in 34% of women; these infections included bacteremia due to gram-positive organisms, catheter site infection, cellulitis, pneumonia, oral candidiasis, herpes simplex virus infection, and vaginitis. Fifty percent of PBPC transplant recipients required hospital admission, usually because of persistent fever; the mean duration of hospitalization was 3 days. No deaths or serious adverse events occurred. Such reduced infectious morbidity may be a consequence of minimal oral and/or gastrointestinal mucositis associated with the conditioning regimen and broad-spectrum antimicrobial prophylaxis used for this patient population.

Formally Defining Medical Processes

OBJECTIVES To demonstrate a technology-based approach to continuously improving the safety of medical processes. METHODS The paper describes the Little-JIL process definition language, originally developed to support software engineering, and shows how it can be used to model medical processes. The paper describes a Little-JIL model of a chemotherapy process and demonstrates how this model, and some process analysis technologies that are also briefly described, can be used to identify process defects that pose safety risks. RESULTS Rigorously modeling medical processes with Little-JIL and applying automated analysis techniques to those models helped identify process defects and vulnerabilities and led to improved processes that were reanalyzed to show that the original defects were no longer present. CONCLUSIONS Creating detailed and precisely defined models of medical processes that are then used as the basis for rigorous analyses can lead to improvements in the safety of these processes.

Cyclophosphamide and paclitaxel as initial or salvage regimen for the mobilization of peripheral blood progenitor cells

Peripheral blood progenitor cells are now commonly used for hematologic reconstitution after myelosuppressive chemotherapy for hematologic and solid malignancies. The purpose of this study was to evaluate the activity of paclitaxel 170 mg/m2 and cyclophosphamide 2 g/m2 (CP) with filgrastim (human G-CSF) for mobilization of PBPCs as the first or second maneuver after failure with filgrastim alone. Sixty-four patients with stage II–IV breast cancer received (CP) followed by filgrastim (10 μg/kg/day). In 35 (55%) this was the first maneuver while it was for salvage in 29 (45%) patients. The median number of aphereses was two (range, 1–7). In 83% of the patients apheresis was initiated on days 10–11 following chemotherapy. The median numbers of CD34+ cells/kg, CD34+ cells/apheresis/kg and total nucleated cells/kg collected were 8.7 × 106 (2.11–73.5), 3.97 × 106 (0.3–36.75) and 164.15 × 108(9–660), respectively. All the patients yielded at least 2 × 106 CD34+ cells/kg. CP mobilization salvaged the 29 patients who failed mobilization with filgrastim alone. When used as first-line mobilization the yield of CD34+ cells × 106/kg was higher than in the salvage group (16.93 vs 3.94, P < 0.001). patients receiving cp as salvage reached the target of 5 × 106 CD34+ cells/kg in only 45% (13/29) of cases vs 94.3% as first maneuver. CP followed by filgrastim is a safe and effective regimen for the mobilization of PBPCs in patients with breast cancer and shows significant activity in patients who failed to mobilize with filgrastim, suggesting a higher mobilization potential.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Breast Cancer

The frequent use of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT) in the treatment of metastatic breast cancer and high-risk primary breast cancer reflects frustration with the outcomes obtained using conventional therapies and the reproducible and generally favorable results being reported from phase 11. single institution phase 111, and registry data. Indeed, transplantation for breast cancer is the leading indication in the United States for stem cell-supported transplantation. Breast cancer is the second leading cause of cancer death among women in the United States, with 180,000 new cases diagnosed annually and 44,000 deaths ( 1 ) . Early detection, surgery, radiation therapy, and chemotherapy have improved the survival expectations of patients with early-stage breast cancer. During the past decade, the paradigm for the conventional treatment of

Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer.

Doxorubicin plus paclitaxel has been shown to be an active regimen for metastatic breast cancer and is now frequently used as adjuvant therapy for high-risk primary breast cancer. Initial studies reported a higher than expected rate of cardiac toxicity with this regimen. We studied 105 patients with either high-risk primary breast cancer or metastatic breast cancer who were treated with doxorubicin (60 mg/m2) and 3-h infusions of paclitaxel (175 mg/m2) cycled every 3 weeks. Patients received three cycles of chemotherapy for high-risk primary or four cycles for metastatic disease. Patients then proceeded to high-dose chemotherapy (HDC) (STAMP I cyclophosphamide, cisplatin and carmustine) and peripheral blood progenitor cell transplantation (PBPCT). Patients underwent radionuclide multi-gated angiograms (MUGA) before and following induction chemotherapy and following HDC. During induction chemotherapy 40 (38%) of the patients had a reduction in left ventricular ejection fraction (LVEF). Fourteen had a decrease of 20% or greater and two were mildly symptomatic from CHF. There was additional reduction in the LVEF after HDC with a median value for LVEF of 59% (range, 20–78%). During HDC 10 patients developed clinical signs of congestive heart failure (CHF). Five patients responded to diuretic therapy and did not require any additional treatment. Four patients responded to vasodilation and/or digoxin with improvement in cardiac function. A clinically significant decrease in cardiac function was found in a small number of patients after induction chemotherapy and HDC with PBPCT. The majority of the patients tolerated this regimen without problems. Although there was a decline in LVEF as measured by radionuclide MUGA this did not prevent the majority of patients from proceeding with HDC. Bone Marrow Transplantation (2000) 25, 1047–1052.

High-dose chemotherapy and CD34-selected peripheral blood progenitor cell transplantation for patients with breast cancer metastatic to bone and/or bone marrow

Fifty women with breast cancer metastatic to bone or bone marrow involvement on light microscopy at the time of initial evaluation were treated with high-dose chemotherapy (HDC) and peripheral blood progenitor cell (PBPC) transplantation with CD34+ cell selection using the Isolex 300i system. All patients received induction chemotherapy. PBPC were mobilized with chemotherapy and granulocyte colony-stimulating factor. The median CD34+ progenitor purity was 94.7% (range 72–98.7%) and recovery 38.4% (range 21–60%). Forty-eight hours after HDC with cyclophosphamide, cisplatin and carmustine, PBPC were reinfused. Median time to neutrophil count >0.5 × 109/l was 9 (range 9–12) days and to platelet transfusion independence 11 (4–30) days. These data demonstrate that selected CD34+ PBPCs allow rapid hematologic reconstitution after HDC. During follow-up, 23% of patients developed herpes zoster. Two patients developed cytomegalovirus infections. Three patients developed fungal infections. The development of these infections was not associated with steroid use but appeared more frequently in patients with diabetes mellitus. Seventy-four per cent of patients received steroids for pulmonary toxicity. Treatment-related mortality was 4%. Progression-free survival and overall survival at 35 months was 22.4% and 40.5%, with a median of 11.4 months and 15.4 months, respectively.Bone Marrow Transplantation (2001) 28, 1023–1029.