Appendix A: Quality and Inefficiency Waste in the Peer-Reviewed Medical Literature
Brent C. James, M.D., M.Stat.
IHC Institute for Health Care Delivery Research
36 S. State Street, 16th Floor
Salt Lake City, Utah 84111-1453
16 August 2000
Clinical quality improvement provides a theory and a set of practical tools for the measurement and management of health care delivery processes. It holds that all planned, human work, including health care delivery, is accomplished through such processes. It posits that every such clinical work process produces parallel medical and cost outcomes. That suggests that medical outcomes are directly related to cost outcomes. Clinical quality improvement describes three causal relationships that define that link. One of those relationships describes processes changes which produce better medical outcomes, but only through higher resource investment and costs. The other two relationships—quality waste and inefficiency waste—generate lower costs by improving medical outcomes, or while medical outcomes hold stable.
Estimates suggest that health care quality waste and inefficiency waste may account for more than 50 percent of all American health care expenditures. Growing pressure on health care costs have therefore generated an obvious interest in quality and inefficiency waste, as means to control costs and possibly expand health care access while maintaining high health care quality. But theory and estimates do not always translate into practice. As a first step, we therefore examined the peer-reviewed medical literature seeking instances showing quality waste and inefficiency waste mechanisms at work within current American health care delivery. Our aim was to see whether such phenomena exist in practice as well as theory, and to get some preliminary sense of their possible scale and, hence, potential.
We sought evidence of quality waste and inefficiency waste in American health care delivery through three sequential investigations:
(1) A convenience sample of documented health care savings arising from the elimination of quality waste or inefficiency waste
We contacted colleagues working in clinical quality improvement, and asked them to share articles describing waste and its elimination in American health care. As part of that effort, we posted a "call for published examples" for two months (August through September, 1999) on the Institute for Healthcare Improvement's (IHI) Web site (www.ihi.org). We also sent a single broadcast e-mail request to all members of the IHI's Quality Management Network (QMN), a consortium of health care delivery systems working to implement quality improvement methods within their internal operations, through the IHI listserve that supports that group.
The results of those requests are shown in Appendix A.
(2) A detailed review of three clinical journals
We reviewed all issues of The New England Journal of Medicine, The Journal of the American Medical Association, and The Joint Commission Journal on Quality Improvement, published during a 32 month time period—January 1, 1997, to August 31, 2000. We identified all articles describing changes in clinical outcomes that also reported measured reductions in the associated costs or charge of care delivery, and classified them as representing quality waste or inefficiency waste.
We chose to review The New England Journal of Medicine and The Journal of the American Medical Association because of their reputation and wide readership among practicing American physicians. We reviewed The Joint Commission Journal on Quality Improvement because we perceived it as a widely read, leading publication within the field of quality improvement itself.
(3) A general Medline search
Using MESH headings identified from articles found during the journal review, we generated a set of Medline search parameters for similar articles. We applied those parameters in a Medline search for all peer-reviewed reports of randomized, controlled clinical trials (RCTs), clinical trials using other study designs, and meta-analyses, for the same 32 month time period from January 1, 1997, through August 31, 2000. That search used the following terms:
- "quality of health care"[MESH] AND "cost savings"[MESH]
- "health care quality access, and evaluation"[MESH] AND "cost savings"[MESH]
- "health care quality access, and evaluation"[MESH] AND "evaluation"[MESH] AND
- "costs and cost analysis/economics"[MESH]
- "health care category"[MESH] AND "cost control"[MESH]
Medline using search terms derived from the foregoing sources 1330 articles that show cost improvements associated with clinical change.
What we didn't review—things like the IHI Breakthrough Series.
Note that this is a "proof of concept," rather than a quantitative assessment.
Note that the measured cost savings do not always accrue to the sponsoring organization, and that they may appear much further along in the care process than the QI intervention.
That said, there is good evidence that quality waste and inefficiency are common in American health care delivery, and that attacking them can produce significant cost savings (at least as illustrated by individual projects where this occurred).
Through conversations with colleagues we discovered a series of clinical trials that explicitly addressed the medical outcomes—cost outcomes relationship. These trials attempted to improve medical outcomes and simultaneously reduce costs, by applying process management methods such as care delivery protocols.
We eliminated a longer list of quality improvement projects that also explicitly related costs to clinical outcomes, because those projects had not yet been reported in peer-reviewed publications.
Those investigators undertaking these trials reported that, in many circumstances, major medical journals were not willing to publish complete cost data, or to explicitly explore the waste mechanisms that drove lower costs.
1. Prevention of adverse drug events
Classen DC, Pestotonik SL, Evans RS, Burke JP. Computerized surveillance of adverse drug events in hospital patients. JAMA 1991; 266:2847-2851.
Pestotnik SL, Classen DC, Evans RS, Stevens LE, Burke JP. Prospective surveillance of imipenem/cilastatin use and associated seizures using a hospital information system. The Annals of Pharmacotherapy 1993; 27:497-501.
Classen DC, Pestotonik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277:301-306.
Case-control study, comparing patients with moderate or severe ADEs to matched controls without ADEs. Estimated marginal additional treatment costs for moderate and severe ADEs were $2262 per case; for severe ADEs alone, $3634 per case. Total excess costs to treat ADEs at study hospital were $4,483,000 over the four years covered by the study. Extended to all hospitals in the United States, estimated annual marginal treatment costs for moderate and severe ADEs of $79 billion. Estimated annual savings from reducing ADEs at study hospital of more than $500,000.
2. Inpatient antibiotic decision support
Pestotnik SL, Evans RS, Burke JP, Gardner RM, Classen DC. Therapeutic antibiotic monitoring: surveillance using a computerized expert system. The American Journal of Medicine 1990; 88:43-48.
Evans RS. The HELP system: a review of clinical applications in infectious diseases and antibiotic use. M.D. Computing 1991; 8:282-288, 315.
Evans RS, Pestotnik SL, Classen DC, Burke JP. Development of an automated antibiotic consultant. M.D. Computing 1993; 10:17-22.
Pestotnik SL, Classen DC, Evans RS, Burke JP. Implementing antibiotic practice guidelines through computer-assisted decision support: clinical and financial outcomes. Ann Intern Med 1996; 124:884-890.
Evans RS, Pestotnik SL, Classen DC, Clemmer TP, Weaver LK, Orme JF, Lloyd JF, Burke JP. A computer-assisted management program for antibiotics and other anti-infective agents N Engl J Med 1998; 338:232-238 (22 Jan).
Between 1988 and 1994, proportion of patients receiving antibiotics increased from 31.8 percent to 53.1 percent in association with health system policies shifting less seriously ill patients to other facilities. Acquisition price of antibiotics increased 15 percent, while use of more expensive front line antibiotics, as a proportion of all antibiotics used, increased from 24 percent to 47 percent. With better antibiotic prescribing (fewer doses and fewer antibiotics per regimen) antibiotic costs fell by $81 per patient treated, from 24.8 percent of total pharmacy medication costs to 12.9 percent of total pharmacy medication costs, and from $987,550 to $612,500 total expense (in 1988 dollars).
3. Prevention of deep surgical wound infections
Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992; 326:281-286.
James BC. Quality improvement in the hospital: managing clinical processes. The Internist 1993; 34:11-13, 17.
Cost savings of more than $700,000 per year, associated with a fall in deep surgical wound infection rates from 1.8 percent to 0.4 percent.
4. Long-term mechanical ventilation
Young MP, Gooder VJ, Oltermann MH, Bohman CB, French TK, James BC. The impact of a multidisciplinary approach on caring for ventilator-dependent patients. International Journal for Quality in Health Care 1998; 10:15-26.
For patients managed on a mechanical ventilator for more than 72 hours in a medical intensive care unit, risk-adjusted cost per case fell by more than $20,000, counting both patients who lived and patients who died. Survival held stable or improved. Total annual savings at the study hospital exceeded $2.5 million.
5. High Frequency Oscillating Ventilation (HFOV) for premature newborns
Gerstmann DR, Minton SD, Stoddard RA, Meredith KS, Monaco F, Bertrand JM, Battisti O, Langhendries P, Francois A, Clark RH. The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Pediatrics 1996; 98:1-14.
Average reduction in hospital costs of $89,300 per case for premature infants with respiratory distress syndrome (RDS) < 1 kg at birth, and $7,400 per case for premature infants with RDS > 1 kg at birth. Total net cost savings at study hospital of $3.7 million per year. Equivalent or superior medical outcomes across 9 major measures.
6. Ventilator management of Acute Respiratory Distress Syndrome (ARDS)
East TD, Morris AH, Wallace J, Clemmer TP, Orme JF Jr., Weaver LK, Henderson S, Sittig DF. A strategy for development of computerized critical care decision support systems. Int J Clin Monit Comput 1992; 8:263-269.
Henderson S, Crapo RO, Wallace CJ, East TD, Morris AH, Gardner RM. Performance of computerized protocols for the management of arterial oxygenation in an intensive care unit. Int J Clin Monit Comput 1992; 8:271-280.
East TD, Bohm SH, Wallace CJ, Clemmer TP, Weaver LK, Orme JF Jr., Morris AH. A successful computerized protocol for clinical management of pressure control inverse ratio ventilation in ARDS patients. Chest 1992; 101:697-710.
Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr., Weaver LK, Dean NC, Thomas F, East TD, Pace NL, Suchyta MR, Beck E, Bombino M, Sittig DF, Bohm S, Hoffmann B, Becks H, Butler S, Pearl J, Rasmusson B. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994; 149:295-305.
Documented average hospital cost savings of $23,600 per case, with equivalent or superior survival outcomes as compared to next most viable alternative therapy (ECCO2R); estimated annual savings of $295 million per year if applied to all ARDS patients treated in the United States.
7. Improving core clinical processes in tertiary critical care
Clemmer, Terry P., Spuhler, Vicki J., Oniki, Thomas A., Horn, Susan D. Results of a collaborative quality improvement program on outcomes and costs in a tertiary critical care unit. Crit Care Med 1999; 27(9):1768-1774.
Clemmer, Terry P., Spuhler, Vicki J. Developing and gaining acceptance for patient care protocols. New Horiz 1998; 6(1):12-19 (Society of Critical Care Medicine).
Significant improvements in glucose control, use of enteral feeding, antibiotic use, ARDS survival, laboratory use, blood gas use, radiograph use, and appropriate use of sedation. A severity-adjusted cost reduction of more than $2.5 million per year in 1991 dollars, or about 30 percent of total patient care costs. For those cost centers directly addressed, a documented cost reduction of 87 percent.
8. Enteral feedings in pediatric ICU
Chellis MJ. Sanders SV. Webster H. Dean JM. Jackson D. Early enteral feeding in the pediatric intensive care unit. J Parenteral & Enteral Nutrition 1996; 20(1):71-3 (Jan-Feb).
Chellis MJ. Sanders SV. Dean JM. Jackson D. Bedside transpyloric tube placement in the pediatric intensive care unit. J Parenteral & Enteral Nutrition 1996; 20(1):88-90 (Jan-Feb).
Harrison AM, Clay B, Grant MJ, Sanders SV, Webster HF, Reading JC, Dean JM, Witte MK. Nonradiographic assessment of enteral feeding tube position. Crit Care Med 1997; 25(12):2055-9 (Dec).
In addition to the specific clinical quality improvement projects listed above, colleagues also identified the following peer-reviewed articles reporting an association between better clinical outcomes and reduced cost outcomes:
1. Gheiler EL, Lovisolo JAJ, Tiguert R, Tefilli MV, Grayson T, Oldford G, Powell IJ, Famiglietti G, Banerjee M, Pontes JE, Wood DP Jr. Results of a clinical care pathway for radical prostatectomy patients in an open hospital- multiphysician system. European Urology 1999; 35:210-216.
2. Weingarten SR, Riedinger MS, Conner L, Lee TH, Hoffman I, Johnson B, Ellrodt AG. Practice guidelines and reminders to reduce duration of hospital stay patients with chest pain: an interventional trial. Ann Int Med 1994; 120:257-263.
3. Cooper CJ, El-Shiekh, Cohen DJ, Blaesing L, Burket MW, Basu A, Moore JA. Effect of transradial access on quality of life and cost of cardiac catheterization: a randomized comparison. Am Heart J 1999; 138:430-436.
4. Noguchi T, Miyazaki S, Yasuda S, Bab T, Sumida H, Morii I, Daikoku S, Goto Y, Nonogi H. A randomized controlled trial of prostar plus for haemostasis in patients after coronary angioplasty. Eur J Vasc Endovasc Surg 2000; 19:451-455.
5. Miccoli P, Bendinelli C, Berti P, Viginali E, Pinchera A, Marcocci C. Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study. Surgery 1999; 126(6):117-121.
6. Roth A, Malov M, Carthy Z, Golovner M, Naveh R, Alroy I, Kaplinsky E, Lanaido S. Potential reduction costs and hospital emergency department visits resulting from prehospital transtelephonic triage B the Shahal experience in Israel. Clin Cardiol 2000; 23:217-276.
7. Kainen P, Koicukangas P, Ohinmaa A, Koivukangas J, Öhman J. Cost-effectiveness analysis of nimodipine treatment after aneurysmal subarachnoid hemorrhage and surgery. Neurosurgery 1999; 45:780-785.
8. Stoller J, Mascha EJ, Kester L, Haney D. Randomized controlled trial of physician-directed versus respiratory therapy consult service-directed respiratory care to adult non-ICU inpatients. Am J Respir Crit Care Med 1998; 158:1068-1075.
9. Falcon T, Paraiso MFR, Mascha E. Prospective randomized clinical trial of laparoscopically assisted vaginal hysterectomy versus total abdominal hysterectomy. Am J Obstet Gynecol 1999; 180(4):955-962.
10. Jones C, Palmer TE, Griffeths RD. Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 1999;15(2):108-115.
11. Rosenheck R, Cramer J, Xu W, Graowski J, Douyon R, Thomas J, Henderson W, Charney D. Multiple outcome assessment in a study of the cost-effectiveness of clozapine in the treatment of refractory schizophrenia. Health Serv Res 1998; 33:1237-1261.
12. Heikkinen TJ, Haukipuro K, Koivukangas P, Hulkko A. A prospective randomized outcome and cost comparison of totally extraperitoneal endoscopic hernioplasty versus lichtenstein hernia operation among employed patients. Surg Laprarosc Endosc 1998; 8(5):338-344.
13. Heikkinen TJ, Haukipuro K, Hulkko A. A cost and outcome comparison between laparoscopic and lichtenstein hernia operations in a day-case unit: a randomized prospective study. Surg Endosc 1998; 12:1199-1203.
14. Tyrer P, Evans K, Gandhi EV, Lamont A, Harrison-Read P, Johnson T. Randomized controlled trial of two models of care for discharged psychiatric patients. BMJ 1998; 316:106-109.
15. Kirten OC, DeHaven B, Morgan J, Morejon O, Civetta J. A prospective, randomized comparison of an in-line heat moisture exchange filter and heated wire humidifiers: rates of ventilator-associated early-onset(community-acquired) or late-onset(hospital acquired) pneumonia and incidence of endotracheal tube occlusion. Chest 1997; 112:1055-1059.
16. Choong PFM, Langford AK, Dowsey MM, Santamaria NM. Clinical pathway for fractured neck of femur: a prospective, controlled study. MJA 2000; 172:423-426.
17. Heikkinen M, Aarnio P, Hannukainen J. Percutaneous dilational tracheostomy or conventional surgical tracheostomy? Crit Care Med 2000; 28(5):1399-1402.
18. Haaga JR, Nakamoto D, Stellato T, Novak RD, Gavent ML, Silverman SG, Bellmore M. Intracavity urokinase for enhancement of percutaneous abscess drainage: phase II trial. AJR Am J Roentgenol 2000; 174:1681-1685.
19. Kollef MH, Shapiro SD, Silver P, St John RE Prentice D, Sauer S, Ahrens TS, Shannon W, Baker-Clinkscale D. A randomized, controlled-trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med 1997; 25(4):567¬574.
20. Smith TJ, Hillner BE, Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A, Link H, Zander A, Yanovich S, Kitchin R, Erder MH. Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma. J Clin Oncol 1997; 15(1):5-10.
21. Carere RG, Webb JG, Buller CEH, Wilson M, Rahman T, Spinelli J, Anis AH. Suture closure of femoral arterial puncture sites after coronary angioplasty followed by same-day discharge. Am Heart J 2000; 139:52-58.
22. Laroche C, Fairbairn I, Moss H, Pepke-Zaba J, Sharples L, Flower C, Coulden R. Role of computed tomographic scanning if the thorax prior to bronchoscopy in the investigation of suspected lung cancer. Thorax 2000 May; 23:271-276.
23. Stuck AE, Minder CE, Peter-Wuest I, Gillman G, Egli C, Kesselring A, Leu RE, Beck JC A randomized trial of in-home visits for disability prevention in community-dwelling older people at low and high risk for nursing home admission. Archives of Internal Medicine 2000 Apr 10; 160:107-113.
24. Casati V, Guzzon D, Oppizzi M, Cossolini M, Torri G, Calori G, Alfieri O. Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery. Annals of Thoracic Surgery. 1999 Dec; 68:2252-2256.
25. Stowers SA, Eisenstein EL, Th Whackers FJ, Berman DS, Blackshear JL, Jones AD Jr, Szymanski TJ Jr, Lam LC, Simons TA, Natale D, Paige KA, Wagner GS. An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: results from a randomized trial. Annals of Emergency Medicine 2000 Jan; 35:17-25.
26. Lacey L, Hopkinson PK, Montainer J, Leblanc F, Gill MJ. An evaluation of the cost effectiveness of adding lamivudine to zidovudine-containing regimens in HIV infection. Canadian perspective. Pharmacoeconomics 1999; 15 Suppl 1:55-66.
27. Lacey L, Youle M, Truemen P, Staszewski S, Schrappe M, Behrens M. A prospective evaluation of the cost effectiveness of adding lamivudine to zidovudine-containing antiretroviral treatment regimens in HIV infection. European perspective. Pharmacoeconomics 1999; 15 Suppl 1:39-53.
28. Lacey L, Mauskopf J, Lindrooth R, Pham S, Sang M, Sawyer W. A prospective cost-consequence analysis of adding lamivudine to zidovudine-containing antiretroviral treatment regimens for HIV infection in the US. Pharmacoeconomics 1999; 15 Suppl 1:23-37.
29. Stewart S, Marley JE, Horowitz JD. Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure; a randomised controlled study. Lancet 1999 Sep 25; 354:1077¬1083.
30. de Clerk GJ, van Steijn JH, Lobatto S, Jaspers CA, van Veldhuizen WC, Hensing CA, Bunnik MC, Geraedts WH, Dofferhoff AS, Van Den Berg J, Melis JH, Hoepelman AI. A randomised, multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory infections. International Journal of Antimicrobial Agents 1999 Jul; 12:121-127.
31. Boldt J, Weber A, Mailer K, Papsdorf M, Schuster P. Acute normovolaemic haemodilution vs controlled hypotension for reducing the use of allogenic blood in patients undergoing radical prostatectomy. British Journal of Anaesthesia 1999 Feb; 82:170-174.
32. Rosenheck R, Cramer J, Allan E, Erdos J, Frishman LK, XU W, Thomas J, Henderson W, Charney D. Cost-effectiveness of clozapine in patients with high and low levels of hospital use. Archives of General Psychiatry 1999 Jun; 56:565-572.
33. Guthrie E, Moorey J, Margison F, Barker H, Palmer S, McGrath G, Tomenson B, Creed F. Cost-effectiveness of brief psychodynamic-interpersonal therapy in high utilizers of psychiatric services. Archives of General Psychiatry 1999 Jun; 56:519-526.
34. Stewart S, Vandenbroek AJ, Pearson S, Horowitz JD. Prolonged beneficial effects of a home-based intervention on unplanned readmissions and mortality among patients with congestive heart failure. Archives of Internal Medicine 1999 Feb; 159:257-261.
35. Yeh CC, Yu JC, Wu CT, Ho ST, Chang TM, Wong CS. Thoracic epidural anesthesia for pain relief and postoperation recovery with modified radical mastectomy. World Journal of Surgery 1999 Mar; 23:256-260.
36. Fass R, Fennerty MB, Ofman JJ, Gralnek IM, Johnson C, Camargo E, Sampliner RE. The clinical and economic value of a short course of omeprazole in patients with noncardiac chest pain. Gastroenterology 1998 Jul; 115:42-49.
37. Bernabei R, Landi F, Gambassi G, Sgadari A, Zuccula G, Mor V, Rubenstein LZ, Carbonin P. Randomised trial of impact of model of integrated care and case management for older people living in the community. British Medical Journal 1998 May 2; 316:1348-1351.
38. Sanchez Garcia M, Cambronero Galache JA, Lopez Diaz J, Cerda Cerda E, Rubio Blasco J, Gomez Aguinaga MA, Nunez Reiz A, Rogero Marin S, Onoro Canaveral JJ, Sacristan del Castillo JA. Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial. American Journal of Respiratory Critical Care Medicine 1998 Sep; 158: 908-916.
39. Mark DB, Cowper PA, Berkowitz SD, Davidson-Ray L, DeLong ER, Turpie AG, Califf RM, Weatherly B, Cohen M. Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events [unstable angina or non-Q-wave myocardial infarction]. Circulation 1998 May; 5:1702-1707.
40. Jalan R, Forrest EH, Stanley AJ, Redhead DN, Forbes J, Dillon JF, MacGilchrist AJ, Finlayson ND, Hayes PC. A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices. Hepatology 1997 Nov; 26:1115-1122.
41. Meyer DM, Jessen ME, Wait MA, Estrera AS. Early evacuation of traumatic retained hemothoraces using thorascotherapy: a prospective, randomized trial. Annals of Thoracic Surgery 1997 Nov; 64:1396-1400.
42. York R, Brown LP, Samuels P, Finkler SA, Jacobsen B, Persely CA, Swank A, Robbins D. A randomized trial of early discharge and nurse specialist transitional follow-up care of high-risk childbearing women. Nursing Research Sep/Oct 1997; 46:254-261.
43. Kirton OC, DeHaven B, Morgan J, Morejon O, Civetta J. A prospective, randomized comparison of an in-line heat moisture exchange filter and heated wire humidifiers: rates of ventilator-associated early-onset (community-acquired) or late-onset (hospital acquired) pneumonia and incidence of endotracheal tube occlusion. Chest 1997 Oct; 112:1055-1059.
44. Wake N, Hisashige A, Katayama T, Kishikawa H, Ohkubo Y, Sakai M, Araki E, Shichiri M. Cost-effectiveness of intensive insulin therapy for type 2 diabetes: a 10-year follow-up of the Kumamoto study. Diabetes Research and Clinical Practice 2000 Jun; 48:201-210.
45. Sacristan JA, Gilaberte I, Boto B, Buesching DP, Obenchain RL, Demitrack M, Perez Sola V, Alvarez E, Artigas F. Cost-effectiveness of fluoxetine plus pindolol in patients with major depressive disorder: results from a randomized double-blind clinical trial. Institute of Clinical Pharmacology 2000 Mar; 15:107-113.
46. Tunis SL, Johnstone BM, Gibson PJ, Loosbrock DL, Dulisse BK. Changes in perceived health and functioning as a cost-effectiveness measure for olanzapine versus haloperidol treatment of schizophrenia. Journal of Clinical Psychiatry 1999; 60:38-45.
47. Swart EL, van Schijndel RJ, von Loenen AC, Thijis LG. Continuous infusion of lorazepam versus medazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective. Critical Care Medicine 1999 Aug; 27:1461-1465.
48. Sonnennberg A, Pauly MP, Levenson SD, Schwartz JS. Antibiotic therapy of Helicobacter pylori infection reduces healthcare expenditures related to duodenal cancer. American Journal of Managed Care 1999 Jan; 5:53-59.
49. Caldwell JW, Singh S, Johnson RH. Clinical and economic evaluation of subsequent infection following intravenous ciprofloxacin or imipenem therapy in hospitalized patients with severe pneumonia. Journal of Antimicrobial Chemotherapy 1999 Mar; 43 Suppl A:129-134.
50. Laloux P, Vakaet A, Monseu G, Jacquy J, Bourgeois P, van der Linden C. Subcutaneous sumatriptan compared with usual acute treatments for migraine: clinical and pharmacoeconomic evaluation. Acta Neurologica Belgica 1998 Dec; 98:332-341.
51. Dallas MJ, Bowling D, Roig JC, Auestad N, Neu J. Enteral glutamine supplementation for very-low-birth-weight infants decreases hospital costs. JPEN Journal of Parenteral Enteral Nutrition 1998 Nov-Dec; 22:352-356.
52. Grines CL, Marsalese DL, Brodie B, Griffin J, Donohue B, Costantini CR, Balestrini C, Stone G, Wharton T, Esente P, Spain M, Moses J, Nobuyoshi M, Ayres M, Jones D, Mason D, Sachs D, Grines LL, O'Neill W. Safety and cost-effectiveness of early discharge after primary angioplasty in low risk patients with acute myocardial infarction. PAMI-II Investigators. Primary Angioplasty in Myocardial Infarction. Journal of the American College of Cardiology 1998 Apr; 31:967-972.
53. Cook JR, Glick HA, Gerth W, Kinosian B, Kostis JB. The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction. American Journal of Hypertension 1998 Dec; 11:1433-1441.
54. Rydman RJ, Isola ML, Roberts RR, Zalenski RJ, McDermott MF, Murphy DG, McCarren MM, Kampe LM. Emergency Department Observation Unit versus hospital inpatient care for a chronic asthmatic population: a randomized trial of health status outcome and cost. Medical Care 1998 April; 36:599-609.
55. Kollef MH, Shapiro SD, Silver P, St. John RE, Prentice D, Sauer S, Ahrens TS, Shannon W, Baker-Clinkscale D. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Critical Care Medicine 1997 April; 25:567-574.
56. Smith TJ, Hillner BE, Schmitz N, Linch DC, Dregger P, Goldstone AH, Boogaerts MA, Ferrant A, Link H, Zander A, Yanovich S, Kitchin R, Erder MH. Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma. Journal of Clinical Oncology 1997 Jan; 15:5-10.
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