Measuring the cost of care in benign prostatic hyperplasia using time-driven activity-based costing (TDABC).

BACKGROUND: Determining '"value'" in health care, defined as outcomes per unit cost, depends on accurately measuring cost. We used time-driven activity-based costing (TDABC) to determine the cost of care in men with benign prostatic hyperplasia (BPH) - a common urologic condition. METHODS: We implemented TDABC across the entire care pathway for BPH including primary and specialist care in both inpatient and outpatient settings. A team of expert stakeholders created detailed process maps, determined space and product costs, and calculated personnel capacity cost rates. A model pathway was derived from practice guidelines and calculated costs were applied. RESULTS: Although listed as 'optional' in practice guidelines, invasive diagnostic testing can increase costs by 150% compared with the standalone urology clinic visit. Of five different surgical options, a 400% cost discrepancy exists between the most and least expensive treatments. CONCLUSIONS: TDABC can be used to measure cost across an entire care pathway in a large academic medical center. Sizable cost variation exists between diagnostic and surgical modalities for men with BPH. IMPLICATIONS: As financial risk is shifted toward providers, understanding the cost of care will be vital. Future work is needed to determine outcome discrepancy between the diagnostic and surgical modalities in BPH.

Use of patient ethnography to support quality improvement in benign prostatic hyperplasia.

BACKGROUND: Patient-centeredness is a primary aim of quality improvement (QI) but optimal strategies to achieve that goal remain elusive. Benign prostatic hyperplasia (BPH) is one of the commonest urologic diagnoses and significantly affects quality of life. Patient ethnography is an emerging qualitative method of observation and dynamic interviews to understand the context through which the patient experiences care. We implemented patient ethnography to support our QI infrastructure and improve patient-centeredness in BPH. PROBLEM: Little is known about how to measure whether processes of care are patient-centered. We did not know whether the care processes our patients experienced provided value from their perspective. GOALS: We sought to discover previously unrecognized components of care that patients perceived to be of low value. Our primary goal was to develop QI initiatives that targeted low-value themes identified in the ethnography. Our secondary goal was a rapid rollout of three targeted initiatives. STRATEGY: We used a 4-step patient ethnography: (1) created detailed process maps to define phases of care, (2) interviewed patients, (3) synthesized transcript data in focus groups using the Crawford Slip method, and (4) targeted undesirable components of care for QI. Semi-structured interviews with seven representative patients identified low-value themes. Focus groups, comprised of primary care physicians, case coordinators, nurses, and urologists, evaluated the interview transcripts and generated improvement opportunities prioritized based on feasibility, patient value, scalability, and innovation. We used affinity mapping and priority matrix techniques to prioritize QI opportunities. RESULTS: We identified five low-value themes from the patient interviews and developed corresponding QI opportunities. These included issues surrounding the referral and consultation process as well as postoperative care, especially home urinary catheter maintenance. Six months after completing the ethnography three of five targeted improvement opportunities had been implemented.

High-risk endometrial cancer in young indigent women.

OBJECTIVE: The aim of this study was to evaluate a different prevalence and clinical pattern of high-risk endometrial cancer in an indigent population of young women. METHODS: Charts of 71 consecutive patients, treated for endometrial adenocarcinoma during a 6-year period, were reviewed. The patients were divided into two groups contingent upon age--(i) those who were below 40 years and (ii) those who were over 40. Based on histological type, grade, and stage, both groups were subdivided into a low, intermediate, or high-risk cancer category. RESULTS: Of the 13 (18.3%) patients in the younger age group, five patients (38.4%) had high-risk endometrial cancer, compared to only eight patients (13.8%) in the older age group. CONCLUSION: In contradiction to previous reports, our results show that a higher proportion of young indigent women diagnosed with endometrial cancer have a high-risk cancer. Delay in diagnosis can explain only some of the discrepancies in the special clinical pattern of endometrial cancer among this population. Other possible explanations include nutritional differences, genetic susceptibility, immunological status, and high-risk behavior. More epidemiological studies are needed for complete understanding of the unfavorable outcome of endometrial cancer in these young women.

Uterine evacuation with misoprostol during radiotherapy for cervical cancer in pregnancy.

Radiotherapy as definitive treatment for invasive cervical cancer during pregnancy causes spontaneous abortion in most cases. Surgical evacuation of the uterus is indicated when abortion does not occur, exposing patients to additional morbidity. Two Latin American women, diagnosed with FIGO stage IB2 cervical cancer at approximately 15 weeks gestation, underwent radiotherapy with radiosensitizing chemotherapy. After intrauterine fetal demise was detected, both women underwent induction with misoprostol. Results included one complete abortion and one incomplete abortion without complications or delays in treatment. These cases demonstrate that induction with misoprostol appears to be a safe and effective alternative to surgical evacuation of the uterus when spontaneous abortion fails to occur during radiotherapy for locally advanced cervical cancer.

Adenovirus-mediated thymidine kinase gene therapy in combination with topotecan for patients with recurrent ovarian cancer: 2.5-year follow-up.

OBJECTIVE: Patients with recurrent ovarian cancer were treated intraperitoneally (ip) with a replication-deficient recombinant adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene. Vector delivery was followed by intravenous administration of an antiherpetic prodrug and a topoisomerase I inhibitor. METHODS: Ten patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal ip flow received delivery of ip ADV. Two patients each were treated on dose level 1 (2 x 10(10) vector particles), dose level 2 (2 x 10(11)), and dose level 3 (2 x 10(12)); four patients were on dose level 4 (2 x 10(13)). Acyclovir and topotecan were started 24 h after vector delivery. Five patients underwent second-look surgery about 4 weeks after application of gene therapy (GT). RESULTS: At the time of the second-look surgery, two out of five patients were free of tumor. Four weeks after GT none of the peritoneal biopsies showed residual vector DNA. Patients pretreated with an average of three different chemotherapeutic drugs and two different chemotherapy regimens had a median overall survival (OS) of 18.5 months. Three patients are still alive 30, 30, and 31 months after GT. CONCLUSION: With the combination of secondary optimal debulking, GT, and topotecan, median OS was about one-third longer than in previously reported second-and third-line trials. Survival was comparable to that of patients of other studies with secondary cytoreductive surgery in combination with chemotherapy.

Primary choriocarcinoma of the vulva.

Primary extrauterine choriocarcinoma is very rare, found mostly in the genital tract (tube, cervix, ovary, vagina). Other sites such as lungs, gastrointestinal tract, heart, brain and submentum also have been reported. A 31-year-old woman presented with abnormal uterine bleeding 6 weeks after her last menstrual cycle. Her HCG titer level was 900 mIu/ml. She underwent dilation and curettage (D & C). Pathology failed to reveal any chorionic villi. Further evaluation was done, including a second D & C, laparoscopy, exploratory laparotomy, CT, MRI and ultrasound which all failed to define a source for the elevated HCG titer which subsequently rose to 95,000 mIu/ml 130 days after her last menstrual cycle. At that time a vulvar mass was observed. Fine needle aspiration (FNA) was positive for choriocarcinoma. The patient was treated with one course of methotrexate 60 mg intramuscularly every other day for 5 days. Actinomycin-D 0.5 mg given intravenously daily for 5 days was added to courses 2-7. Radiotherapy (4000 rads) was applied concomitant with the chemotherapy. The remainder of the mass was subsequently excised. The patient has remained with no evidence of disease for 10 years. This is the first case report of primary vulvar choriocarcinoma.

Concurrent primaries of vaginal clear cell adenocarcinoma and endometrial adenocarcinoma in a 39-year old woman with in utero diethylstilbestrol exposure.

Diethylstilbestrol (DES) was used widely in the late 1940s in an attempt to prevent adverse pregnancy outcomes. In 1971 the US Food and Drug Administration proscribed its use for pregnancy support secondary to its association with clear cell adenocarcinoma of the vagina. Several studies in animal models demonstrated an association with endometrial cancer among offspring following in utero DES exposure. To date, there is only one case report of endometrial cancer in women exposed to DES in utero. We present the first case, to our knowledge, of a woman exposed to DES in utero who presented with double primaries of clear cell cancer of the vagina concomitant with endometrial cancer.

Extensive subcutaneous metastases from squamous cell carcinoma of the cervix in patient with HIV.

Advanced human immunodeficiency viral disease is associated with a high prevalence of cervical squamous intraepithelial and invasive lesions and probably with a rapidly progressive course of disease. Metastases to the skin occur rarely in cervical cancer, even in terminal stage of the disease. A patient with human immunodeficiency virus (HIV) for 14 years was diagnosed with squamous cell cancer of the cervix, Stage I-B2 in June 1997. She underwent successful radiotherapy. She then presented in January 1999 with recurrence evidenced by extensive subcutaneous nodules and multiple metastases. The patient developed rapidly progressive disease and died within two months. Patients with HIV and cervical cancer may present with a more aggressive course of disease. Aggressive treatment and closer follow-up may be indicated.

Bedside multimarker testing for risk stratification in chest pain units: The chest pain evaluation by creatine kinase-MB, myoglobin, and troponin I (CHECKMATE) study.

BACKGROUND: Earlier, rapid evaluation in chest pain units may make patient care more efficient. A multimarker strategy (MMS) testing for several markers of myocardial necrosis with different time-to-positivity profiles also may offer clinical advantages. METHODS AND RESULTS: We prospectively compared bedside quantitative multimarker testing versus local laboratory results (LL) in 1005 patients in 6 chest pain units. Myoglobin, creatine kinase-MB, and troponin I were measured at 0, 3, 6, 9 to 12, and 16 to 24 hours after admission. Two MMS were defined: MMS-1 (all 3 markers) and MMS-2 (creatine kinase-MB and troponin I only). The primary assessment was to relate marker status with 30-day death or infarction. More patients were positive by 24 hours with MMS than with LL (MMS-1, 23.9%; MMS-2, 18.8%; LL, 8.8%; P=0.001, all comparisons), and they became positive sooner with MMS-1 (2.5 hours, P=0.023 versus LL) versus MMS-2 (2.8 hours, P=0.026 versus LL) or LL (3.4 hours). The relation between baseline MMS status and 30-day death or infarction was stronger (MMS-1: positive, 18.8% event rate versus negative, 3.0%, P=0.001; MMS-2: 21.9% versus 3.2%, P=0.001) than that for LL (13.6% versus 5.5%, P=0.038). MMS-1 discriminated 30-day death better (positive, 2.0% versus negative, 0.0%, P=0.007) than MMS-2 (positive, 1.8% versus negative, 0.2%; P=0.055) or LL (positive, 0.0% versus negative, 0.5%; P=1.000). CONCLUSIONS: Rapid multimarker analysis identifies positive patients earlier and provides better risk stratification for mortality than a local laboratory-based, single-marker approach.

Effectiveness and safety of abciximab after failed thrombolytic therapy.

Among 214 patients treated with abciximab within 24 hours of full-dose thrombolytic therapy, major bleeding occurred in 50 patients (23%; 95% confidence interval [CI] 18% to 30%) and intracranial hemorrhage occurred in 3 patients (1.4%; 95% CI 0.3% to 4%). The independent multivariate predictors of major bleeding were age (odds ratio [OR] 1.53/10 years, 95% CI 1.05 to 2.21, p = 0.03), time from thrombolytic to abciximab (OR 0.91/hour, 95% CI 0.83 to 0.99, p = 0.03), and intra-aortic balloon pump insertion (OR 4.42, 95% CI 2.00 to 9.72, p = 0.0002).

University of Kentucky community-based field experience: program description.

Community-based field experiences (CBFE) provide students with exemplary experiential learning opportunities. The purposes of this paper are to describe the University of Kentucky College of Dentistry (UKCD) CBFE and report the results of a two-year, self-report survey that assessed the primary course goal, students' perceptions of change in knowledge and skills related to nineteen areas of patient care (n = 90, 100% return rate), and their overall rating of the program. Knowledge and skill data were analyzed using the non-parametric binomial test for comparing proportions. A significant (.05 level) majority of students reported increases in knowledge in all areas to which they were exposed. Descriptive frequencies summarizing the results of the total CBFE experience indicate that the majority of students felt it was a positive experience. The CBFE continues to be a meaningful element in the UKCD curriculum as it provides students with a relevant, authentic educational experience.

Comparison of cardiac troponin T versus creatine kinase-MB for risk stratification in a chest pain evaluation unit.

We evaluated cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) for risk stratification of chest pain unit (CPU) patients. We studied 383 consecutive patients with chest pain assigned to our CPU by emergency department physicians. At baseline all had normal or nondiagnostic electrocardiograms, no high-risk clinical features, and negative CK/CK-MB. CK-MB and electrocardiograms were taken at 0, 4, 8, and 12 hours and cTnT at 0, 4, and 8 hours. Eight patients (2.1%) were CK-MB positive and 39 (10.2%) were cTnT positive, including all but 1 CK-MB-positive patient. All marker-positive patients were detected by 8 hours. Seven cTnT-positive patients and 1 cTnT-negative patient had myocardial infarction (p <0.0001). cTnT-positive patients were older, less likely to be women or smokers, and more often had diabetes mellitus or known coronary disease (CAD). Seventy-one percent of patients underwent diagnostic testing. cTnT-positive patients more often underwent angiography (46% vs 20%) and underwent stress testing less often (28% vs 57%) than cTnT-negative patients. When performed, their stress tests were more often positive (46% vs 14%) and they more often had angiographically significant lesions (89% vs 49%) and multivessel disease (67% vs 29%). There were no short-term deaths. Long-term mortality was higher in cTnT-positive patients (27% vs 7%, p <0.0001). Thus, cTnT identified more CPU patients with myocardial necrosis and multivessel CAD than CK-MB and a population with high long-term mortality risk. Routine use of cTnT in CPUs could facilitate risk stratification and management.

Thymidine kinase (TK) gene therapy of solid tumors: valacyclovir facilitates outpatient treatment.

BACKGROUND: In a Phase I study replication-deficient adenovirus containing the herpes simplex virus (HSV) thymidine kinase (TK) gene (AdV-HSV-TK) was instilled intraperitoneally in patients with recurrent ovarian cancer. Patients were treated with Acyclovir (ACV) or Valacyclovir (VCV) as enzymatic substrates. The purpose of this study was to compare serum levels of ACV and VCV. PATIENTS AND METHODS: The antiherpetic prodrug and Topotecan (1.0 mg/m2 over 30 minutes each day for 5 days) were started 24 hours after vector application. Eight patients received ACV (15 mg/kg i.v. over one hour every 8 hours for 42 doses), two patients were started on ACV for 5 days and then switched to oral VCV (2 g every 8 hours for a total of 42 doses). Blood samples were obtained 20 minutes prior to each drug. RESULTS: Serum levels of ACV and VCV (converted to ACV) were comparable. CONCLUSIONS: Suicide gene therapy with TK is under investigation in a variety of solid tumors. Replacing ACV by VCV will offer a cost-effective alternative and will significantly reduce duration of hospital stay improving quality of life and facilitating an outpatient gene therapy concept.

Cardiac markers: point of care testing.

Point-of-care (POC) or "near-patient" testing allows diagnostic assays to be performed in locations such as the emergency department or intensive care unit where treatment decisions are made and care is delivered based on the results of these assays. Presently, there exist POC immunoassays for several cardiac markers including creatine kinase MB (CK-MB), myoglobin, troponin I, and troponin T that yield qualitative and quantitative results comparable to traditional central lab assays. In the evaluation of emergency room patients with chest pain, POC cardiac markers may improve triage and clinical outcomes. Existing POC assays combining myoglobin and CK-MB have high sensitivity and specificity for diagnosing acute myocardial infarction and may provide the earliest identification of myocardial injury. POC Troponin T assays are the most studied POC cardiac marker assays. Along with POC troponin I assays, these tests provide more sensitive identification of myocardial injury and valuable prognostic information. Prior studies of POC cardiac marker assays have not addressed whether POC testing affects patient outcome or process of care. In situations in which caregivers base triage, treatment and monitoring decisions on time-sensitive diagnostic results, POC tests linked with improved triage and treatment strategies may improve resource utilization and clinical outcomes.

Psychological impact of receiving negative BRCA1 mutation test results in Ashkenazim.

PURPOSE: Most DNA test results for breast/ovarian cancer susceptibility are negative. Because negative test results might be interpreted incorrectly and may have serious psychological and behavioral implications, determining the psychological impact of such results is important. METHODS: A community-based sample of 289 Ashkenazim was tested for 185delAG. The 199 mutation-negatives provided data at baseline and follow-up. Increased risk participants included those who received negative test results but remained at increased risk because positive family and/or personal histories of breast or ovarian cancer made the results uninformative. Average risk meant those who tested negative and had negative family and personal histories of breast or ovarian cancer. Using a logistic regression analysis, both groups' psychological distress levels were compared at baseline and at 1 and 6 months after notification of DNA test results. RESULTS: A logistic regression analysis showed significant but small differences in cancer-specific distress after 6 months between increased and average risk participants (P < 0.006). Increased risk participants reported more distress than average risk. General distress declined among all participants after 1 month. Although baseline and follow-up differences in cancer-specific distress obtained by the increased and average risk participants were statistically significant, none of the absolute levels observed reflected especially high degrees of stress. CONCLUSIONS: Receipt of negative DNA test results does not have a deleterious psychological impact, whether results are informative or uninformative.

Telomere length in human white blood cells remains constant with age and is shorter in breast cancer patients.

BACKGROUND: Telomeres, which are TTAGGG repeats at the end of the eukaryotic chromosome, are essential for complete DNA replication. Telomere length has been reported to decrease in peripheral WBC, unlike the telomerase activity found in these cells. The purpose of this study was to investigate whether telomere length in WBC is indeed age dependent and could serve as a genetic marker in breast or ovarian cancer. METHODS: Five age groups: 20-29; 30-39; 4049; 50-59 and > or = 60 years were examined. The cancer patients were 18 women with ovarian cancer and 18 women with breast cancer. Southern blot analysis of the DNA from peripheral white blood cells (WBC) was performed using 32P-labeled (TTAGGG)3 probe. Blots were scanned in a phosphoimager and analyzed by computer-assisted image analysis. RESULTS: No statistically significant correlation was observed between telomere length and age in either healthy females or cancer patients. However, significantly shorter median telomere length was found in WBC obtained from breast cancer patients as compared to healthy individuals and ovarian cancer patients. CONCLUSIONS: It is concluded that telomere length in WBC is not age dependent, but is significantly shorter in breast cancer patients.

Phase I-II study of combined 5-fluorouracil and cisplatin chemotherapy and altered fractionation radiotherapy for advanced squamous cell carcinoma of the cervix.

Forty patients with advanced carcinoma of the cervix were prospectively treated by an intermodality approach using chemotherapy combination concomitant with split-course hyperfractionated radiation therapy (RT). Cisplatin (CDDP) (60 mg/m2) was administered before radiotherapy initiation followed by 5-fluorouracil (5-FU) (750 mg/m2) for 5 days during the first week of irradiation. The same schedule was repeated in the last week of the RT, with 5-FU administration (1,000 mg/m2) for only 3 days. RT consisted of 5,020 cGy to the pelvis, followed by two intracavitary applications for a total of 5,000-5,500 mg/h radium equivalent when possible: 140 cGy/fraction was administered in the morning and evening, with a 6-h interval. The remainder of the external beam radiation was delivered at a standard daily fractionation of 180 cGy/fraction to a total dose of 5,020 cGy. This regimen of RT with concomitant chemotherapy had minimal toxicity and did not cause significant prolongation of the treatment program. However, a high rate of late complications was noted in patients who had extended-field RT due to paraaortic lymph node involvement. Thirty-two patients had complete response (CR) (80%). 24 (75%) of whom have no evidence disease (NED), with a median follow-up of 24 months. Our study suggests that this regimen of combined chemotherapy and RT in this group of patients with poor prognosis is effective and well tolerated, with acceptable acute toxicity and late morbidity.

Human epithelial ovarian cancer xenotransplants into nude mice can be cured by adenovirus-mediated thymidine kinase gene therapy.

BACKGROUND: Adenovirus-mediated suicide gene therapy of ovarian cancer has effective anti-tumor effects in vitro and in vivo. By transduction of ovarian adenocarcinoma with the Herpes Simplex Thymidine Kinase gene and subsequent treatment with the antiviral agent ganciclovir, prolongation of survival has been described in nude mice. So far, however, in animal models of solid tumors no cures have been reported after gene therapy. METHODS: In a prospective randomized experimental design 76 mice with xenotransplanted serous ovarian carcinoma were treated with three different doses of ADV/RSV-TK at three different time points followed by intraperitoneal ganciclovir administration. The experiment was designed to show significance of survival differences upon doubling of the number of survived days at a p-value of 0.05 with a power of 80%. The endpoint of the trial was survival. RESULTS: Treatment response was seen in all treated animals evident by significant prolongation of survival. Treatment response was dependent on the therapeutic viral dose and the tumor burden of the animal at the time of treatment. Two out of eight mice with early disease have now survived ten months without evidence of disease with untreated animals dying after nineteen days. Subcutaneous tumor development at the injection site was the reason of death in the remaining six mice of this group. CONCLUSIONS: Intraperitoneal ADV/RSV-TK suicide gene therapy of epithelial ovarian cancer in combination with ganciclovir administration can cure nude mice with early disease. This treatment modality may lend itself to incorporation into the current treatment concept of human ovarian malignancy. Clinical trials are warranted.

Identification of a meiotically expressed carbohydrate antigen in ovarian carcinoma: I. Immunohistochemical localization.

A monoclonal antibody developed against a meiotically expressed porcine oocyte carbohydrate antigen has been shown to recognize an antigen in ovarian surface epithelial cells. Immunohistochemical studies of ovaries demonstrated that this antigen is present in the ovarian surface epithelia (OSE) of numerous mammalian species, including the non-human primate and the human (1). Although most of the ovarian surface epithelial cells are lost during aging in the human, a few cells may remain in ovarian crypts. In view of theories that most ovarian carcinomas are derived from the OSE cells in aging women, the PS1 antibody has been used to evaluate ovarian tumors using immunocytochemistry to detect the PS1 antigen in paraffin embedded pathology tissues. The present study found that the PS1 antigen is abundant in a number of malignant ovarian tumors, but is not expressed in a non-malignant Brenner's (ovarian) tumor or granulosa cell tumors. This antibody therefore appears to have great potential for the histopathological and immunochemical analysis of ovarian tumors.