[18F]fluorodeoxyglucose positron emission tomography/computed tomography in combination with clinical data in predicting overall survival in non-small-cell lung cancer patients: A retrospective study.

INTRODUCTION: Positron emission tomography/computed tomography (PET/CT) has an established role in evaluating patients with lung cancer. The aim of this work was to assess the predictive capability of [18F]Fluorodeoxyglucose ([18F]FDG) PET/CT parameters on overall survival (OS) in lung cancer patients using an artificial neural network (ANN) in parallel with conventional statistical analysis. METHODS: Retrospective analysis was performed on a group of 165 lung cancer patients (98M, 67F). PET features associated with the primary tumor: maximum and mean standardized uptake value (SUVmax, SUVmean), total lesion glycolysis (TLG) metabolic tumor volume (MTV) and area under the curve-cumulative SUV histogram (AUC-CSH) and metastatic lesions (SUVmaxtotal, SUVmeantotal, TLGtotal, and MTVtotal) were evaluated. In parallel with conventional statistical analysis (Chi-Square analysis for nominal data, Student's t test for continuous data), the data was evaluated using an ANN. There were 97 input variables in 165 patients using a binary classification of either below, or greater than/equal to median survival post primary diagnosis. Additionally, phantom study was performed to assess the most optimal contouring method. RESULTS: Males had statistically higher SUVmax (mean: 10.7 vs 8.9; p = 0.020), MTV (mean: 66.5 cm3 vs. 21.5 cm3; p = 0.001), TLG (mean 404.7 vs. 115.0; p = 0.003), TLGtotal (mean: 946.7 vs. 433.3; p = 0.014) and MTVtotal (mean: 242.0 cm3 vs. 103.7 cm3; p = 0.027) than females. The ANN after training and validation was optimised with a final architecture of 4 scaling layer inputs (TLGtotal, SUVmaxtotal, SUVmeantotal and disease stage) and receiving operator characteristic (ROC) analysis demonstrated an AUC of 0.764 (sensitivity of 92.3%, specificity of 57.1%). CONCLUSION: Conventional statistical analysis and the ANN provided concordant findings in relation to variables that predict decreased survival. The ANN provided a weighted algorithm of the 4 key features to predict decreased survival. IMPLICATION FOR PRACTICE: Identification of parameters which can predict survival in lung cancer patients might be helpful in choosing the group of patients who require closer look during the follow-up.

A multicenter drug use surveillance of intravenous immunoglobulin utilization in US academic health centers.

BACKGROUND: The role of intravenous immunoglobulin (IVIG) in treating a variety of diseases is controversial and under active investigation for at least two reasons: first, a severe shortage of IVIG products exists in the US; second, numerous off-label (not specified in the Food and Drug Administration [FDA]-approved label) uses for IVIG have been, and continue to be, described in the literature. However, most off-label uses are not supported by evidence from properly designed clinical trials. OBJECTIVE: To assess inpatient use of IVIG in a sample of US academic health centers and to compare it with published evidence-based model guidelines for IVIG use. METHODS: Data on the use of IVIG and subsequent clinical outcomes in 251 patients were collected prospectively from 12 institutions. Recommendations from consensus guidelines were used to categorize patients who received IVIG into one of four groups: labeled uses; off-label, recommended; off-label, recommended as alternative; and off-label, not recommended. Outcomes were scored according to guideline criteria. RESULTS: One hundred seven patients (43%) received IVIG for indications contained in the FDA-approved product label, 130 patients (52%) received IVIG for off-label indications, and 14 (5%) received undefined treatment. Among all patients administered IVIG, 31 (12%) were treated for off-label recommended reasons; 64 (26%) received off-label recommended as alternative therapy; and 35 (14%) received off-label not recommended therapy, as defined by model guidelines. Outcomes were not significantly different between the groups. CONCLUSIONS: Our findings suggest that IVIG continues to be used to treat a wide variety of conditions not specified in the product label. Furthermore, a substantial proportion of the reported off-label uses are not recommended according to evidence-based guidelines.

Clinical and economic outcomes of coronary angioplasty alone or in combination with stents in academic health centers: a retrospective database analysis.

OBJECTIVES: Indications for the use of stents are evolving and their optimal place in therapy remains to be defined. The objective was to compare the 1-year clinical and economic outcomes of percutaneous transluminal coronary agioplasty (PTCA) with and without the use of stents. METHODS: This retrospective database analysis was conducted using data from 60 US academic medical centers in 1996 and 1997. Outcomes of interest included in-hospital mortality (both on sentinel and readmission visits), readmission rates, revascularization procedures, length of stay, and the cost of sentinel and readmission hospitalization. RESULTS: A total of 27,020 patients either did (n = 13,254) or did not (n = 13,766) receive coronary stents in conjunction with PTCA. The median cost of hospitalization for the stent group was about dollar 1,409 higher (mean, dollar 1,200) than the no-stent group and the length of stay was similar (4.3 days vs. 4.5 days, respectively, P = .2628). Mortality rates on readmission (0.9% stent vs. 0.8% no-stent, P = NS) did not differ. However, patients in the stent group had better mortality rates compared to the no-stent group during the sentinel visit (1.7% vs. 2.7%, P < .001). Stent use was not associated with a significantly lower risk of a revascularization procedure on readmission to the same institution (OR 0.95, 95% CI 0.87-1.04, P = .28). CONCLUSIONS: Stents were associated with a 1% decrease of inpatient mortality during the sentinel visit without impacting length of stay or readmission rates. This advantage was associated with a dollar 1,409 higher median cost of hospitalization in the stent group.

Noncompliance with drug therapy for chronic obstructive pulmonary disease: a risk factor for hospitalization?

OBJECTIVE: To determine if patients who were noncompliant with prescribed medications for chronic obstructive pulmonary disease (COPD) had higher rates of hospitalization. METHODS: A retrospective case-control study was performed in a tertiary-care university-affiliated Veterans Administration Health Care System setting. Subjects included 93 patients hospitalized for exacerbation of COPD and 93 controls with a diagnosis of COPD who did not require hospitalization. Utilizing pharmacy prescription fill records, medication noncompliance rates of patients who required hospitalization for exacerbation of COPD were compared with patients who did not require such hospitalization. RESULTS: The mean noncompliance ratio for the hospitalized patients was lower than the ratio for the controls (0.19 vs. 0.20) although the difference was not statistically significant (P = .95). There was no statistically significant difference between the demographics of the two groups. However, the patients who were hospitalized had a significantly greater number of COPD and nonCOPD medications (P < .0001, P < .0001) prescribed. They also had significantly more nonCOPD admissions and lengths of stay (P = .02, P = .01). CONCLUSION: At the levels of medication noncompliance observed in this population, there was no difference in rates of hospitalization. Hospitalization could be attributed to other causes such as severity of illness and existence of other comorbid conditions. The effects of environmental pollution and cigarette smoking were not studied. KEYWORDS: chronic obstructive pulmonary disease; hospitalization, noncompliance; risk factors.

Transmyocardial laser revascularization: a qualitative systematic review.

OBJECTIVE: To evaluate the status of transmyocardial laser revascularization (TMLR) from an evidence-based perspective to help hospitals make resource management decisions. STUDY DESIGN: Qualitative systematic review of the clinical literature. METHODS: We searched the reference databases MEDLINE, BIOSIS, EMBASE, SciSearch, and Current Contents to identify all articles related to TMLR published between January 1985 and March 1997. We collected, analyzed, and summarized clinical studies in evidence tables. RESULTS: The cumulative evidence available in the medical literature regarding the safety and effectiveness of TMLR encompasses approximately 2000 patients treated worldwide, primarily those with medically refractory angina. Preliminary data suggest that TMLR has an acceptable survival rate and effectively relieves angina in approximately 75% of patients. Data showing improved myocardial perfusion, cardiac function, or prognosis are inconclusive. The mechanism by which TMLR relieves angina is not yet known. CONCLUSIONS: Early evidence regarding TMLR suggests it will be useful for treating patients with end-stage coronary artery disease. Definitive recommendations await critical analysis of the results of ongoing randomized clinical trials, post-market surveillance studies, and third-party payer acceptance.

Recombinant human growth hormone for AIDS-associated wasting.

OBJECTIVE: To review the current literature regarding the role of recombinant human growth hormone (rhGH) in the treatment of AIDS-associated wasting and to briefly describe alternative therapies. DATA SOURCES: A literature search was performed on MEDLINE and AIDSLINE for the period from January 1985 through September 1997. Key words used in the search strategy were growth hormone, human immunodeficiency virus, acquired immune deficiency syndrome, wasting, and weight gain. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in this review. Abstracts were included only when they were judged to add critical information. Thereafter, the inclusion was restricted to English-language articles and abstracts on clinical trials and human studies in AIDS-associated wasting. DATA SYNTHESIS: Body wasting, characterized by an involuntary loss of body cell mass, is a well-recognized feature of many chronic diseases, including infection with HIV AIDS-associated wasting is a metabolic disorder characterized by weight loss, depletion of lean body mass (LBM), and preservation of body fat, leading to muscle weakness and organ failure. rhGH has been approved by the Food and Drug Administration for use in treating AIDS-associated wasting. The adverse event profile is similar to that of other rhGH products. The recommended dosage of rhGH is 4-6 mg administered by subcutaneous injection daily. It offers a more expensive alternative to appetite stimulants such as megestrol acetate and dronabinol. CONCLUSIONS: Trials with rhGH on the control of wasting in patients with AIDS have been encouraging, but with limited conclusive evidence of sustainable positive outcomes. Studies demonstrate that rhGH increases LBM and decrease adipose tissue, but how these translate into long-term outcomes such as decreased hospitalization, morbidity, and mortality has yet to be determined. A formal health economic assessment is needed to properly determine the impact of rhGH on the healthcare system.

Muromonab-CD3 and antithymocyte globulin in renal transplantation.

OBJECTIVE: To review the recently published medical literature for the practical and efficient use of muromonab-CD3 (OKT-3) and antithymocyte globulin (ATG) in renal transplantation. DATA SOURCES: MEDLINE and EMBASE were searched (1985-February 1996). Key words used were antithymocyte globulin (ATG, Atgam), muromonab-CD3 (OKT-3, Orthoclone), and kidney transplantation. Thereafter, the search was restricted to English-language articles, clinical trials, and human studies. STUDY SELECTION AND DATA EXTRACTION: The search was reviewed for articles of interest, and pertinent references from these articles were further reviewed to supplement the initial search. The review focused on antibody therapy as induction and/or rejection therapy in renal transplantation. DATA SYNTHESIS: Although ATG and OKT-3 are effective in delaying and reducing the occurrence of acute rejection, their impact on long-term graft survival has not been established. Improved graft survival has, however, been demonstrated in patients at high risk for rejection. These risks are described in the review. As first-line or steroid-resistant rejection therapy, ATG and OKT-3 have proven efficacious. Some studies have shown improved graft survival with OKT-3. Although serious infections may occur, OKT-3 has been shown to be effective in reversing rejections resistant to both steroids and ATG. Therefore, reserving OKT-3 for steroid- or ATG-resistant rejections may be preferred over the first-line use of OKT-3, which is limited by the development of antimurine antibodies with subsequent uses. However, the benefits of first-line antibody therapy may outweigh the risks of developing these antibodies in patients for whom high-dose steroids may not be the most appropriate treatment. Other factors that need to be considered are adverse effects, which appear to be lower with ATG, cost, and total hospital charges. The accuracy of treatment outcomes analysis among these studies is limited by variations in the immunosuppressive regimens of the study centers, doses of concomitant therapies, use of prophylactic antibiotics, and time to follow-up. CONCLUSIONS: While important benefits are realized from using antibody therapies in renal transplantation, their use is often associated with excess immunosuppression and increased treatment costs. Despite encouraging results from published trials, questions regarding the extent of their prophylactic use and impact on long-term outcomes need to be answered. The current literature contains no prospective, controlled, randomized comparisons of OKT-3 and ATG with standardized regimens of conventional immunosuppressive agents and antirejection protocols. The majority of studies use OKT-3 as part of the treatment protocol. Well-designed studies using ATG are lacking. Further research is needed to refine treatment protocols for ATG and OKT-3 to determine the optimal timing and dosing for these agents.

A primer on the assessment of medical technologies.

As health care costs continue to escalate, the assessment and management of medical technologies have become vitally important to health care providers. Evaluation and comparison of the safety, effectiveness, efficiency, cost, and clinical outcomes of new and existing technologies provide the critical information necessary to make appropriate clinical resource decisions in an increasingly cost-conscious environment. Technologies to be assessed include pharmaceuticals, devices, medical and surgical procedures, and health care delivery systems. Clinical trial results, literature reviews, expert opinions, and group consensus are used in preparing technology use decisions, which often include the preparation of background information, specific recommendations, use guidelines, and reimbursement analyses.

The clinical effectiveness and financial impact of utilizing peripheral blood progenitor cells as rescue therapy following autologous bone marrow transplant.

The use of peripheral blood progenitor cell transplant as rescue therapy after high-dose chemotherapy and autologous bone marrow transplant significantly decreases transfusion, laboratory, room, and total charges. An improvement in clinical indicators also points toward decreased patient morbidity. Additional cost reductions may be realized by greater utilization of outpatient care, thereby further reducing room and total charges.

Albumin and nonprotein colloid solution use in US academic health centers.

BACKGROUND: Crystalloids, nonprotein colloids (NPCs), and albumin are used for many indications. The use of the least costly agent in situations where these products are clinically interchangeable can reduce health care costs. OBJECTIVES: To characterize the prescribing of albumin and NPC. To evaluate the appropriateness and cost implications of their use. METHODS: An observational study conducted in 15 academic health centers from April 11 through May 6, 1994, to assess the appropriateness of albumin and NPC use, based on "model" consensus-derived indication guidelines. RESULTS: A total of 969 case report forms were evaluated. Albumin and NPCs were administered in 83% and 17% of the cases, respectively. Albumin and NPCs were administered mostly in the intensive care (50%) or operating room (31%) settings. The most common prescribers of these products were surgeons (45%) and anesthesiologists (20%). In 87% of cases, albumin or NPC was administered to reach a defined end point (eg, to achieve a target physiological state or to resolve a pathophysiological condition). Only one albumin recipient experienced an adverse event; no adverse events were noted with NPC administration. Approximately $203,000 was spent on albumin and NPC therapy for the 969 cases; $49,702 (24%) was spent on appropriate administrations, $124,939 (62%) on inappropriate administrations, and $28,014 (14%) on unevaluated indications. CONCLUSIONS: Evaluated against model guidelines, most of the albumin and NPC use in the study was found to be inappropriate. The need for institutions to define and implement guidelines that focus on the cost-efficient use of these agents is recommended in an increasingly cost-conscious health care environment.

Recommendations for off-label use of intravenously administered immunoglobulin preparations. University Hospital Consortium Expert Panel for Off-Label Use of Polyvalent Intravenously Administered Immunoglobulin Preparations.

OBJECTIVE: To summarize consensus recommendations for off-label uses of standard intravenous immunoglobulin (IVIG), as developed by a University Hospital Consortium (UHC) Expert Panel. These findings are intended to help guide clinicians in the appropriate and efficient use of IVIG. PARTICIPANTS: The UHC-sponsored panel included eight physicians (board certified in critical care, hematology, immunology, neurology, oncology, pediatrics, or rheumatology) and two hospital pharmacists. EVIDENCE: MEDLINE and EMBASE were searched to identify all English-language review articles (n = 201) and original reports (n = 1904) on IVIG (human use only, excluding editorials, letters, and comments) published between January 1982 and March 1994. Relevant original reports (250) and review articles (87) were evaluated by the first author (T.A.R.). Extracted data included laboratory and clinical findings, objective measures, or clinical impressions. The evidence quality was graded by study design according to the US Preventive Services Task Force. CONSENSUS PROCESS: Before the panel meeting, a draft literature review and recommendations were produced by one of the authors (T.A.R.). The recommendations herein represent consensus (100% agreement) based on the published evidence. CONCLUSIONS: The UHC Expert Panel made specific recommendations for 53 off-label indications and the following general recommendations: (1) Usually IVIG is indicated only if standard approaches have failed, become intolerable, or are contraindicated; (2) IVIG products should be considered therapeutically equivalent and interchangeable; (3) interproduct pharmaceutical differences should be considered with the patient's clinical and physiological status when selecting an IVIG product; and (4) currently, IVIG manufacturers cannot guarantee freedom from viral contamination in the finished product.

Survey results from academic health center intensive care units: considerations for departments of pharmacy.

Using survey data collected from 24 University Hospital Consortium member institutions, this paper examines the role of pharmacy in quality-improvement and cost-reduction initiatives in academic health center intensive care units. The results illustrate that most institutions are not taking full advantage of the services a clinical pharmacy has to offer, and that using these services could improve the quality and cost-efficiency of care.

Surveillance of colony-stimulating factor use in US academic health centers.

OBJECTIVE: To characterize and evaluate hematopoietic colony-stimulating factor (CSF) use, including cost implications, in US academic health centers. DESIGN: An observational study of patients who received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) from September 1 to October 15, 1993. SETTING: Thirty academic health centers in the US. PARTICIPANTS: Five hundred sixty-five patients were evaluated. MAIN OUTCOME MEASURES: The appropriateness of CSF use was assessed, based on consensus-derived indication guidelines and the Food and Drug Administration-approved product labeling. Indication, type of CSF, and dosage were considered in determining the appropriateness of CSF therapy. RESULTS: Based on indication evaluation criteria, 71% of CSF use was appropriate, 7% was inappropriate, and 22% was unproven, although the majority of unproven use was deemed promising by the expert panel. Based on dosage evaluation criteria, 51% of CSF use was appropriate, 27% was inappropriate, and 22% was for promising and other unproven indications. More than 90% of the patients studied received G-CSF. Approximately 3.4% of patients who received G-CSF had an adverse event, compared with 22% of those who received GM-CSF. Approximately $791,000 was spent on CSF therapy in the 565 patients: $401,000 (51%) on appropriate indications and doses, $160,000 (20%) on inappropriate doses for appropriate indications, $124,000 (16%) on promising indications, and $106,000 (13%) on unproven or inappropriate indications. CONCLUSIONS: Substantial costs are incurred currently for CSF therapy without adequate literature support. Further studies are warranted to justify promising but unproven uses of CSFs, as well as to clarify proper dosing, monitoring, and relative safety of CSFs.

A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions.

OBJECTIVE: To develop contemporary, comprehensive guidelines for the appropriate and efficient use of albumin, nonprotein colloid, and crystalloid solutions. DESIGN: A systematic, literature-based, consensus exercise employing a modified Delphi method. PARTICIPANTS: Thirty-one medical and allied health professionals from 26 University Hospital Consortium (Oak Brook, Ill) member institutions were initially chosen to participate. Participants were selected on the basis of their recognized research in the use of albumin, nonprotein colloid, and crystalloid solutions, and/or experience in the review of appropriateness of such use. A total of 24 participants completed the exercise. MAIN OUTCOME MEASURES: Group responses were statistically analyzed in an iterative consensus development process. Five separate questionnaire rounds were designed to establish criteria for the appropriate use of albumin, nonprotein colloid, and crystalloid solutions. RESULTS: Consensus guidelines were developed outlining the appropriate use of these products for 12 clinical indications, including hemorrhagic shock, nonhemorrhagic (maldistributive) shock, hepatic resection, thermal injury, cerebral ischemia, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis. CONCLUSIONS: The Delphi method, a systematic, literature-based consensus process, was shown to be useful in the development of complex clinical practice guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. It is anticipated that the guidelines will assist health care providers to develop local institutional policies and procedures for the appropriate and efficient use of albumin and albumin alternatives. Institutions reviewing and updating existing local guidelines may use the University Hospital Consortium guidelines as a model for comparison.

Evaluation of ondansetron prescribing in US academic medical centers.

BACKGROUND: The study objectives were to characterize the use of the antiemetic ondansetron, a serotonin subtype 3 receptor antagonist, in US academic medical centers, and to assess ondansetron prescribing with consensus-derived prescribing guidelines used as evaluation criteria. METHODS: A multicenter, prospective, observational study was conducted in the inpatient and outpatient care areas of 23 US academic medical centers. A total of 670 patients received ondansetron (508 inpatients and 162 outpatients). The use of ondansetron was compared with consensus-derived prescribing guidelines on the basis of indication for use and dose administered. RESULTS: Only 253 (37.8%) of the 670 patients satisfied for prescribing guidelines for both indication for use and dose administered. The remainder of the patients did not satisfy the guidelines, in whole or in part. If all ondansetron use had met the prescribing guidelines in the patients studied, a reduction in ondansetron use of 31% (16 185/52 260 mg) would have been realized. At an estimated cost of $5 per milligram, this reduction represents a potential cost savings of nearly $81,000, or $121 per patient studied. CONCLUSION: Since its introduction in 1991, ondansetron has become a commonly used antiemetic in US academic medical centers. Although ondansetron is safe and effective in improving patients' tolerance of emetogenic therapies, including cancer chemotherapy, its high cost has added a significant burden to the pharmaceutical budgets of many institutions. The study data suggest that compliance with ondansetron prescribing guidelines, with elimination of indiscriminant use, could result in significant cost savings.