Deep brain stimulation in intraoperative MRI environment - comparison of imaging techniques and electrode fixation methods.

We performed 118 consecutive DBS cases from November 1999 to June 2002. Intraoperatively there were 10 cases studied with fluoroscopy, 73 with 0.2 Tesla (T) MRI and 35 with 1.5 T MRI. Ten electrodes were secured by Medtronic caps, 25 by methyl methacrylate with titanium miniplates, and 82 by Navigus caps. The 3-dimensional displacement between the planned target and actual electrode position (3DD) was determined by fusing the postoperative MRI with the preoperative imaging. The 3DD for using Medtronic caps, methyl methacrylate with miniplates, and Navigus caps were 4.80 +/- 3.16, 2.64 +/- 1.26 and 2.23 +/- 1.15 mm (mean +/- SD), respectively. Navigus caps had statistically significant accuracy (P = 0.03) in holding the electrode when compared with Medtronic caps, and it facilitated electrode revision. The fixation devices significantly affect the final vertical position of the electrode. The 3DD for fluoroscopy, 0.2 T and 1.5 T MRI cases were 4.80 +/- 3.16, 2.31 +/- 1.21 and 2.34 +/- 1.14 mm (mean +/- SD), respectively. No statistically significant difference (P = 0.91) in 3DD was demonstrated between 0.2 T and 1.5 T MRI cases. The presence of intraoperative 1.5 T MRI allowed near real-time electrode position confirmation and early detection of hemorrhagic complications. Satisfactory microelectrode recording was feasible in low-field 0.2 T and high-field 1.5 T MRI environments. Further studies on performing DBS in real-time intraoperative MRI are warranted.

Functional neurosurgery in the MRI environment.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of microelectrode recording, electrical stimulation, and electrode position checking during functional neurosurgical procedures (DBS, lesion) in the interventional magnetic resonance imaging (iMRI) environment. METHODS: Seventy-six surgical procedures for DBS implant or radiofrequency lesion were performed in an open 0.2 T MRI operating room. DBS implants were performed in 54 patients (72 surgical procedures) and unilateral radiofrequency lesions in three for a total of 76 surgeries in 57 patients. Electrophysiological studies including macrostimulation and microelectrode recordings for localization were obtained in the 0.5 to 10 mT fringes of the magnetic field in 51 surgeries. MRI confirmation of the electrode position during the procedure was performed after electrophysiological localization. RESULTS: The magnetic field associated with the MRI scanner did not contribute significant noise to microelectrode recordings. Anatomical confirmation of electrode position was possible within the MRI artifact from the DBS hardware. Symptomatic hemorrhage was detected in two (2.6 %) patients during the operation. Image quality of the 0.2 T MRI scan was sub-optimal for anatomical localization. However, image fusion with pre-operative scans permitted excellent visualization of the DBS electrode tip in relation to the higher quality 1.5 T MRI anatomical scans. CONCLUSION: This study shows that conventional stereotactic localization, microelectrode recordings, electrical stimulation, implant of DBS hardware, and radiofrequency lesion placement are possible in the open 0.2 T iMRI environment. The convenience of having an imaging modality that can visualize the brain during the operation is ideal for stereotactic procedures.

Noninvasive linear accelerator radiosurgery as the primary treatment for trigeminal neuralgia.

The application of a dedicated linear accelerator (DLINAC) as a noninvasive surgical treatment for trigeminal neuralgia has not yet been demonstrated. This work evaluates the outcome and indications of 22 patients submitted to DLINAC radiosurgery as a primary treatment for essential trigeminal neuralgia. At last follow-up evaluation, 21 patients (95.5%) had sustained significant pain relief. DLINAC radiosurgery is safe and effective as a primary noninvasive surgical treatment for selected patients with essential trigeminal neuralgia.

Cost-Utility analysis of tissue plasminogen activator therapy for acute ischaemic stroke: a Canadian healthcare perspective.

BACKGROUND: There are over 40000 ischaemic strokes annually in Canada, which result in significant morbidity, mortality and burden to the healthcare system. A recent, large clinical trial has evaluated tissue plasminogen activator (t-PA) intravenously for the treatment of acute ischaemic stroke with promising outcomes but with an increased risk of symptomatic intracranial haemorrhage. OBJECTIVE: To compare clinical and economic outcomes of intravenous t-PA therapy (0.9 mg/kg, to a maximum of 90 mg, initiated within 3 hours of stroke onset) versus no t-PA for acute ischaemic stroke based on the outcomes achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. DESIGN: A Markov model depicting the natural lifetime course after an initial acute ischaemic stroke. On the basis of this model, a simulated trial compared no t-PA with t-PA. PATIENTS: A hypothetical cohort of 1000 patients with acute ischaemic stroke. STUDY PERSPECTIVE: Canadian healthcare system. OUTCOME MEASURES: Total acute stroke and post-stroke treatment costs and cumulative quality-adjusted life-years (QALYs). RESULTS: For a hypothetical cohort of 1000 patients, the estimated lifetime stroke costs were 103100000 Canadian dollars (SCan) [1999 values) in the t-PA arm ($Can103100 per patient) compared with SCan106900000 in the no t-PA arm ($Can106900 per patient), yielding a lifetime cost difference of $Can3800000 in favour of t-PA versus no t-PA (SCan3800 per patient). In the hypothetical cohort, t-PA treatment resulted in 13 130 QALYs versus 9670 QALYs with no t-PA treatment. This translated into a net benefit of 3460 additional QALYs per 1000 patients (3.46 QALYs per patient). No treatment, outcome or economic variables influenced the model outcome. CONCLUSION: From the standpoint of cost effectiveness, treatment of acute ischaemic stroke with intravenous t-PA is an economically attractive strategy.

Radiosurgery and stereotactic radiation therapy of skull base meningiomas: proposal of a grading system.

OBJECTIVE: The development of a grading system to guide treatment selection, and predict treatment difficulty and outcome of skull base meningiomas infiltrating the cavernous sinus which are managed by stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT), based on an 8-year experience with stereotactic radiation of skull base meningiomas. METHODS: T1 gadoliniun-enhanced magnetic resonance imaging (MRI) of 40 patients with skull base meningiomas, with or without prior surgery, who underwent radiosurgery or stereotactic radiation therapy from 1991 to 1998 at the UCLA Medical Center were reviewed, and the result of treatment was related to the tumor grade. Grade was based on tumor infiltration of the cavernous sinus and extension into adjacent structures. Treatment was performed with a linac-based system. The dose prescribed to the periphery of the tumor for SRS patients (n = 34) ranged from 12 to 22 Gy, and the maximum dose delivered to the tumor ranged from 24 to 46 Gy. SRT (n = 6). Treatment was planned using a single isocenter, usually prescribed to the 90% isodose volume, bringing the fractionation scheme to the maximal tolerance of the optic apparatus. The periphery dose ranged from 24 to 46 Gy with a maximum dose of 45 to 51 Gy. Clinical and MRI follow-up was performed every six months for the first 3 years and every year thereafter. RESULTS: Grade I meningiomas were restricted to the cavernous sinus (n = 12). Grade II cavernous sinus meningiomas extended to the clivus and/or the petrous bone, without compression of the brainstem (n = 9). Grade III meningiomas had superior and/or anterior extension with compression of the optic nerve or tract (n = 9). Grade IV tumors compressed the brain stem (n = 8), and Grade V were bilateral lesions (n = 2). Tumor control rates were 90% for Grade I, 86% for Grade II, 86% for Grade III, 42% for Grade IV and no control for tumors Grade V. Complications were not related to tumor grade. CONCLUSION: This grading system correlated with outcome and difficulty in planning radiosurgery. Failure of treatment was more likely to occur in patients with higher Grade tumors.

Influence of the British Columbia reference drug program on hospital formularies: a survey of hospital pharmacy managers.

OBJECTIVES: To assess the impact of the British Columbia Reference Drug (RD) Program on the management of hospital formularies in the province. MATERIALS AND METHODS: A survey of pharmacy managers in British Columbia hospitals with more than 100 beds was conducted in November, 1997. The survey instrument contained questions regarding hospital characteristics, drugs listed on the formulary before and after implementation of RD policies for four drug classes, the hospitals' responses to RD policies and the respondents' opinions of the RD Program. RESULTS: Thirty-two (86%) hospitals returned the survey by the stated deadline. Before the RD Program was implemented, significantly more hospitals listed cimetidine (P=0.03), felodipine (P<0.001), quinapril (P<0.001) and ramipril (P<0.001) on the hospital drug formulary. The main reasons given for changes to hospital drug formularies were community prescribing patterns (25% to 38%) and the RD Program (23% to 44%) depending on the drug category. Twenty-seven (84%) hospitals did not automatically adopt RD policies; 22 (69%) hospitals reviewed the policies at Pharmacy and Therapeutics Committee meetings. Sixteen (50%) respondents thought that hospitals should change their drug formularies to match the policies. Median satisfaction with the RD Program on a 10-point rating scale (1 = unsatisfied, 10 = satisfied) was 7 (range 2 to 10). CONCLUSIONS: Respondents appeared to be neutral when asked their opinion of the RD initiative. The RD policies resulted in drug category-dependent changes in the hospital formulary listings. H2 receptor antagonists and antihypertensives were the most significantly influenced drug categories. RD status does not automatically confer formulary status of a drug; however, it does appear to be a criterion in most hospitals when considering a drug for inclusion in the formulary.

A new ciprofloxacin stepdown program in the treatment of high-risk febrile neutropenia: a clinical and economic analysis.

STUDY OBJECTIVE: To determine treatment outcomes and economic impact of a ciprofloxacin stepdown program for high-risk febrile neutropenic adults from the hospital's perspective. DESIGN: Unblinded, two-phase, single-center study. SETTING: Adult leukemia and stem cell transplant unit. PATIENTS: High-risk adults with febrile neutropenia. INTERVENTION: Two conditions were analyzed: a multidisciplinary ciprofloxacin stepdown program involving a reduction in parenteral ciprofloxacin dose from 400 to 200 mg (i.v.-i.v.) and conversion to oral ciprofloxacin (i.v.-p.o.) when criteria were met; and no i.v.-i.v. stepdown program. MEASUREMENTS AND MAIN RESULTS: Forty-six sequential treatment courses were compared with 42 treatment course from 6-month periods in preintervention (P1) and postintervention (P2) phases. Assessed parameters were clinical and microbiologic outcomes, adverse drug reactions (ADRs), and direct medical resource use and costs (1998 $Canadian) for the episode of febrile neutropenia. A decision analytic model was used to map probabilities and costs and to conduct sensitivity analyses. To supplement standard statistical testing, 1,000 bootstrap samples were created, and the mean cost difference was calculated between phases for each sample. Patient demographics, percentage i.v.-p.o. stepdown, and duration of therapy were similar between phases. Clinical success (83% P1, 81% P2), microbiologic eradication (15% P1, 24% P2), and possible ADRs (6% P1, 9% P2) did not differ. Intravenous-to-intravenous dose stepdown occurred in 33% of P2 and no P1 treatment courses (p<0.001). Resource use and costs were similar between phases, although a reduction was seen in the drug's mean total cost/day ($58 P1, $52 P2, p=0.04). There was also a trend toward a decrease in mean total treatment costs ($4,843 P1, $3,493 P2, p=0.08). In 1,000 bootstrap samples, 99.8% showed a cost advantage for P2. The model was robust to sensitivity analyses. CONCLUSION: This intervention influenced administration of ciprofloxacin without apparent compromise of patient outcomes and resulted in a reduction in total costs of treating febrile neutropenia.

Economic impact of standardized orders for antimicrobial prophylaxis program.

OBJECTIVE: To assess the effect and economic impact of an intervention aimed at standardizing the timing of preoperative antimicrobial prophylaxis from the perspective of a major teaching hospital. DESIGN: A pre/post study design in which a random sample of 60 procedures from a 12-month period in the preintervention phase were reviewed. A comparative sample of 60 procedures during a seven-month postintervention phase was selected. For each prophylactic course, preoperative dose administration details were classified as early (>2 h prior to incision), on time (0-2 h prior), delayed (0-3 h after), or late (>3 after). To determine the economic impact of this intervention, we used a predictive decision analytic model using institutional costs and the published probabilities of inpatient surgical wound infections (SWIs) following administration of antimicrobials timed according to the above criteria. Two conditions were analyzed: (1) an interdisciplinary two-stage therapeutic interchange program involving staff education and modification of preoperative antimicrobial orders to ensure timely administration and (2) no intervention. SETTING: An 1100-bed tertiary care, university-affiliated institution. PATIENTS: 120 randomly selected procedures involving inpatients who received a preoperative antibiotic. OUTCOME MEASURES: Differences in preoperative antimicrobial timing and cost avoidance associated with the intervention. RESULTS: In the preintervention phase, 68% of prophylactic courses were on time, 22% were early, and the balance were delayed or late. The incidence of on-time prophylaxis increased to 97% during the postintervention phase (p = 0.001). Operating room staff involvement in antimicrobial administration increased from 57% to 92% (p = 0.001). Based on a setup and annual intervention cost of $9100 CAN ($1 CAN = $0.68 US), an annual inpatient SWI avoidance of 51 cases, an average infection-associated extended hospital stay of four days, and an average treatment cost of $1957 CAN per inpatient SWI, we estimated that 153 hospital days were avoided and there was an annual cost avoidance of $90 707 CAN ($1779 CAN saved per inpatient infection avoided) due to this intervention. Using sensitivity analyses, no plausible changes in the base case estimates altered the results of the economic model. CONCLUSIONS: An interdisciplinary approach to optimizing the timing of preoperative antimicrobial doses can impact positively on practice patterns and result in substantial cost avoidance. Costs incurred to implement such an intervention are small when compared with the annual cost avoidance to the institution.

Cost analysis of an adult outpatient parenteral antibiotic therapy (OPAT) programme. A Canadian teaching hospital and Ministry of Health perspective.

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) programmes have become prevalent over the past 2 decades. From the US perspective, these programmes have been shown to reduce healthcare costs. No comprehensive analysis has been published from the Canadian perspective. OBJECTIVE: To describe a Canadian OPAT programme for the 3-year period since its inception and to conduct a treatment cost analysis. DESIGN AND METHODS: Demographics and resource utilisation data (health professional labour, laboratory and diagnostic tests, antimicrobials, delivery, home nursing care, catheters and catheter placement) were prospectively collected for enrollees in the OPAT programme over the evaluation period. Avoided hospital resource utilisation was estimated via retrospective chart review by the investigators. Costs were retrospectively assigned to each resource and total cost avoidance by the OPAT programme was determined from each perspective. PERSPECTIVE: A teaching hospital and a provincial Ministry of Health (MOH). MAIN OUTCOME MEASURES AND RESULTS: 140 treatment courses were initiated for 117 adult patients (mean age 54 years) who were enrolled into the programme. Mean pre-OPAT length of hospital stay was 12 days, and mean OPAT duration was 22.5 days. Bone/joint (39%), skin and soft tissue (16%), cardiac (13%) and respiratory tract (12%) infections were the most common infections managed. The most commonly used antimicrobials were vancomycin (29%), cloxacillin +/- gentamicin (22%) and ceftriaxone +/- gentamicin (11%) 85% of enrollees successfully completed their planned antimicrobial treatment regimens. Premature discontinuation of antimicrobial therapy for various reasons occurred in the remaining 15% of courses. The mean cost per treatment course of OPAT was 1910 Canadian dollars ($Can) from the hospital perspective and $Can6326 from the MOH perspective. Assuming that patients would have otherwise completed their antimicrobial therapy in hospital, the mean cost per treatment course was estimated to be $Can14,271. The overall cost avoidance of the OPAT programme was $Can1,730,520 (hospital perspective) and $Can1,009,450 (MOH perspective) over the 3-year assessment period. Sensitivity analyses revealed the results to be robust to plausible changes. CONCLUSIONS: This analysis supports the premise that an adult OPAT programme can substantially reduce healthcare costs in the Canadian healthcare setting.

Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin.

Current protocols for prophylaxis against allograft reinfection after liver transplantation for chronic hepatitis B virus (HBV) infection include the administration of large doses of hepatitis B immune globulin (HBIG), with considerable associated economic costs. Monotherapeutic prophylaxis with lamivudine has been complicated by the development of resistant strains of HBV. We studied the effectiveness of a posttransplantation prophylaxis protocol using combination lamivudine and low-dose HBIG in 7 consecutive patients with chronic HBV infection, 4 of whom were serum HBV DNA positive before pretransplantation lamivudine therapy. All patients were serum HBV DNA negative at transplantation and received lamivudine, 100 mg/d, posttransplantation. HBIG, 2170 IU, was administered intramuscularly intraoperatively and daily for 14 days. Maintenance HBIG therapy consisted of 2170 IU intramuscularly twice weekly, tapered to every 2 to 4 weeks by 12 months posttransplantation. Target serum HBIG (HBV surface antibody) titers were less than 500 IU/L for 6 months, then greater than 300 IU/L until 12 months posttransplantation. Induction serum HBIG titers were determined daily in 5 patients, and both serum HBIG and hepatitis B surface antigen were determined every 4 weeks in all patients. One patient died 61 days posttransplantation; the surviving patients (n = 6) were followed up for a mean of 532 days (range, 395 to 648 days). No patient has developed allograft reinfection. In the induction period, a target HBIG titer of greater than 500 IU/L was not achieved until a mean of 6.8 days (range, 5 to 10 days). In the maintenance period, all patients achieved the target HBIG titer. This suggests combination lamivudine and low-dose HBIG is effective in preventing allograft reinfection by HBV.

Cost-effectiveness of prophylactic dolasetron or droperidol vs rescue therapy in the prevention of PONV in ambulatory gynecologic surgery.

PURPOSE: To assess the cost-effectiveness of prophylactic therapy (1.25 mg droperidol or 50 mg dolasetron i.v.) vs no prophylaxis (rescue therapy) for the prevention of post-operative nausea and vomiting (PONV) from a Canadian hospital perspective. DESIGN: A predictive decision analytic model using previously published clinical and economic evaluations, and costs of medical care in Canada. SUBJECTS: Ambulatory gynecology surgery patients. INTERVENTIONS: Three strategies administered prior to emergence from anesthesia were compared: 1.25 mg droperidol i.v., 50 mg dolasetron i.v.; and no prophylaxis (rescue therapy). RESULTS: The base case mean cost per patient receiving dolasetron prophylaxis was $28.08 CAN compared with $26.88 CAN per patient receiving droperidol prophylaxis, resulting in a marginal cost of $1.20 CAN. This difference translated in an additional cost of $12.00 CAN for the dolasetron strategy per adverse event avoided over the droperidol strategy. The base case mean cost per patient not receiving prophylaxis was $26.92 resulting in marginal costs of $1.16 CAN and $0.04 CAN when compared to dolasetron and droperidol, respectively. Compared with the no prophylaxis strategy, dolasetron prophylaxis resulted in an incremental cost-effectiveness ratio of $5.82 CAN per additional PONV-free patient. The mean costs incurred per PONV-free patient were calculated to be $48.41 for the dolasetron strategy, $46.34 for the droperidol strategy and $70.83 for the no prophylaxis strategy. CONCLUSIONS: Dolasetron and droperidol given intraoperatively were more cost-effective than no prophylaxis for PONV in patients undergoing ambulatory gynecologic surgery. The difference between the two agents was small and favoured droperidol. The model was robust to plausible changes through sensitivity analyses.

Experience with ceftazidime parenteral-to-parenteral dosage stepdown in the empiric treatment of febrile neutropenia.

We assessed the clinical and economic impact of a new parenteral-toparenteral stepdown program involving ceftazidime for the treatment of febrile neutropenia. This was a two-phase (before and after), 12-month, single-center, prospective study with a historical control. Ninety-eight ceftazidime treatment courses (47 preintervention, 51 postintervention) were administered for management of febrile neutropenia in 85 adults with hematologic malignancies. Multidisciplinary creation and promotion of parenteral-to-parenteral ceftazidime stepdown criteria were applied at the discretion of the health care team. Patient demographics between phases were similar. Only 2 (4%) treatment courses before the intervention involved parenteral-to-parenteral dosage stepdown, compared with 34 (67%) after the intervention (p<0.00001). Mean number of total ceftazidime doses/treatment course and mean duration of therapy did not change between phases. Clinical cure or improvement was identified in 74% and 80% of treatment courses before and after the intervention, respectively. The two main reasons for discontinuing the drug before the intervention were recovery of neutrophil count (60%) and adverse reactions (19%). Neutrophil count recovery (59%) and hospital discharge (14%) were the two most common reasons for discontinuation after the intervention. Of 34 stepdown treatment courses after the intervention, 3 (9%) failed to meet established stepdown criteria, and 2 of these required stepdown reversal. Ancillary antibacterial drugs and treatment course outcomes were similar between phases. Total ceftazidime acquisition cost for 704 treatment days in the preintervention phase was $52,473 CAN compared with $54,778 CAN for 907 days of therapy in the postintervention phase. The mean acquisition cost/ceftazidime treatment course was $1100 CAN and did not differ between phases. The mean daily cost of ceftazidime therapy was lower after the intervention ($60.39 vs $74.54 CAN) as a result of a greater frequency of stepdown (p<0.001). Assuming an equivalent number of treatment days, the projected annual acquisition cost avoidance associated with this stepdown program was $19,900 CAN.

Cost-minimization analysis of piperacillin/tazobactam versus imipenem/cilastatin for the treatment of serious infections: a Canadian hospital perspective.

BACKGROUND: In 1998 we reported the first Canadian double-blind, randomized, clinical trial involving a comparison of piperacillin/tazobactam (P/T) with imipenem/cilastatin (I/C). The present study was conducted to determine the feasibility of replacing I/C at our institution. OBJECTIVE: To describe the outcome of a pharmacoeconomic analysis of the clinical trial from the perspective of a tertiary acute-care institution. METHODS: A total of 150 consenting adults originally prescribed I/C were randomly assigned to receive either P/T 4.5 g i.v. (n = 75) or I/C 500 mg i.v. (n = 75) every six hours. Actual direct medical resources used in relation to the treatment of bacterial infections were prospectively assessed during a clinical trial; these included cost of study and ancillary antibiotics, hospitalization, diagnostic testing (radiology, laboratory assessments), and labor, as well as treatment of adverse drug reactions, antibiotic failures, and superinfections. RESULTS: While costs for successful treatment courses were similar across treatment arms, hospitalization costs for treatment course failures were higher for P/T recipients. Direct medical costs for treatment courses associated with a superinfection were also higher in the P/T arm. Overall costs for treatment failures with either study drug were at least twofold those observed for successful treatment courses. Mean total management cost per patient in the P/T group was $15,211 ($ CDN throughout) (95% CI $11,429 to $18,993), compared with $14,232 (95% CI $11,421 to $17,043) in the I/C group (p = 0.32), resulting in a mean cost difference of $979. Sensitivity analyses revealed that the superiority of I/C over P/T for successful treatment of serious infections was sensitive to changes in the cost of hospitalization and drug efficacy for either drug. CONCLUSIONS: Based on the results of the clinical trial, P/T and I/C offer similar clinical, microbiologic, and toxicity outcomes in hospitalized patients with serious infections. Under base-case conditions, our pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T at the dosage regimens studied. However, this finding was sensitive to plausible changes in both clinical and economic parameters.

Cost-effectiveness analysis of enoxaparin versus unfractionated heparin for acute coronary syndromes. A Canadian hospital perspective.

OBJECTIVE: To determine the cost effectiveness of enoxaparin therapy versus unfractionated heparin (UFH) therapy for patients with unstable coronary artery disease from the perspective of a Canadian hospital. DESIGN: A predictive decision analysis model using published clinical and economic evaluations and costs of medical care in Canada. PATIENTS: A hypothetical cohort of patients presenting to hospital with unstable angina or non-Q-wave myocardial infarction as defined by the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. INTERVENTIONS: Two antithrombotic treatment strategies were compared: (i) enoxaparin 1 mg/kg subcutaneously every 12 hours, and (ii) UFH intravenous bolus and constant infusion adjusted to maintain a therapeutic activated partial thromboplastin time. Both treatment strategies included 100 to 325 mg of oral aspirin daily. Enoxaparin or UFH was continued for a minimum of 48 hours to a maximum of 8 days. Cumulative outcomes were considered up to 30 days after initial presentation to hospital. RESULTS: At 30 days, 19.8% of patients who received enoxaparin compared with 23.3% of patients who received UFH reached one of the primary composite events. There was no difference in major bleeding between the 2 treatment groups (6.5% enoxaparin vs 6.8% UFH). The average total direct medical cost per patient was $Can848 with the enoxaparin strategy versus $Can892 with the UFH strategy (1999 values). Therapy with enoxaparin was, therefore, considered to be the dominant strategy. Univariate sensitivity analysis indicated that the decision model was not robust to changes in the 30-day composite end-point, probability of recurrent angina, or base costs for treatment of recurrent angina or enoxaparin therapy. CONCLUSION: Enoxaparin is the dominant antithrombotic pharmacotherapeutic strategy for patients with unstable coronary artery disease.

Cost-effectiveness analysis of abciximab: a Canadian hospital perspective.

OBJECTIVE: To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective. DESIGN: A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada. SUBJECTS: High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial. INTERVENTIONS: Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 micrograms/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA. RESULTS: At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29,700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab. CONCLUSIONS: Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.

Piperacillin/tazobactam versus imipenem: a double-blind, randomized formulary feasibility study at a major teaching hospital.

With the introduction of piperacillin/tazobactam to the North American market, hospitals have been faced with the task of making a decision regarding its formulary role. In view of its broad spectrum of activity, piperacillin/tazobactam could be considered as a formulary alternative to imipenem. To evaluate the formulary feasibility of substituting piperacillin/tazobactam for imipenem, a comparative assessment of these agents in the empiric treatment of serious bacterial infections was undertaken at this tertiary care hospital. This trial was conducted as a randomized, double-blind, single-center study. Consenting adult patients (>16 years of age) who were prescribed imipenem were randomized to receive either 4 g of i.v. piperacillin/tazobactam or imipenem 500 mg of i.v. Q6H with or without concurrent antibiotics. Doses were adjusted according to renal function. There were no restrictions regarding the use of nonstudy antibiotics before and during the study period. Patients with beta-lactam allergies or meningitis or who had received greater than 72 h of previous imipenem therapy were excluded. Patients were evaluated at the end of treatment, at discharge, and at 30 days postdischarge. Endpoints included both clinical and microbiologic efficacy as well as drug toxicity. Over the 433-day study period, 360 imipenem treatment courses were initiated. Of these, 150 treatment courses (75 piperacillin/tazobactam courses and 75 imipenem courses) met study criteria and were subsequently randomized. The distribution of prescriber services for enrolled patients was similar to that for all patients receiving imipenem during the study period (p = 0.15). Also, there were no statistically significant differences in demographic parameters between enrolled and excluded patients. For those patients enrolled in the study, demographic characteristics, treatment course indication(s), and accompanying antibiotics were similar across treatment arms. The mean duration of study drug therapy was 7.7 days (SD, 6.2) for imipenem and 7.5 days (SD, 6.7)for piperacillin/tazobactam (p = 0.84). In the majority of cases, treatment discontinuation occurred as a result of a favorable treatment course outcome, stepdown to a narrower spectrum parenteral agent, or stepdown to an oral agent and did not differ between study drugs (p = 0.73). Clinical and microbiologic treatment course outcomes were also similar across treatment arms. Clinical outcome was deemed successful or improved for 68% of imipenem and 70% of the piperacillin/tazobactam treatment courses (p = 0.54). Fifty-three percent of treatment courses were microbiologically confirmed. Of the 58 courses that were assessed for microbiological outcome, 93% demonstrated successful eradication of the causative pathogens. There was no difference between study drugs (96% imipenem; 90% piperacillin/tazobactam; p = 0.61). The proportion of treatment courses with at least one adverse event was similar between the study drugs (p = 1.0). Nausea and/or vomiting were/was observed more commonly in the imipenem arm (p = 0.03). Discontinuation of therapy due to drug toxicity occurred in 16% of imipenem and 5% of piperacillin/tazobactam treatment courses (p = 0.06). There was no statistically significant difference between the mean treatment course cost for imipenem ($762; range, $55-$3192) versus piperacillin/tazobactam ($696; range, $79-$2967; p = 0.59). In summary, piperacillin/tazobactam seems to represent a suitable alternative to imipenem for several clinical indications including intraabdominal infections, pneumonia, febrile neutropenia, and skin/soft tissue infections in which the causative pathogens are susceptible. However, in view of the prevalence of multiresistant Gram-negative aerobic pathogens at this institution, we do not believe that imipenem can be removed from the drug formulary. In addition, at the currently studied dosing regimen, there seems to be no evidence of a direct cost advantage associated with

A double-blind, randomized study of three antimicrobial regimens in the prevention of infections after elective colorectal surgery.

The objective of this study was to assess the prophylactic efficacy of cefoxitin, ceftizoxime, and metronidazole-gentamicin in colorectal surgery. A double-blind, randomized prospective clinical trial design was used in a Canadian tertiary care teaching hospital. Patients were randomized to one of three treatment groups and received three doses of a study drug (30 min preoperative and 2 postoperative doses at 12 and 24 h). Cefoxitin and ceftizoxime were given as 1000-mg doses. Metronidazole-gentamicin was given as 500 mg of metronidazole plus 120 mg of gentamicin in a minibag. High-risk patients (bowel ischemia, diabetic, current steroid use, etc.) received 10 postoperative doses. Patients with infections, prior antibiotics, or study drug allergies were excluded. Over 30 months, 153 patients were enrolled. Thirty-one patients were excluded for protocol violations. Of the 122 evaluable patients (38 ceftizoxime, 45 metronidazole-gentamicin, 39 cefoxitin), there was no difference across groups regarding sex, age, weight, preoperative Apache II score, and prior history of bowel surgery. Groups were equivalent regarding surgeon, nursing unit, high-risk status (six ceftizoxime, seven metronidazole-gentamicin, seven cefoxitin), bowel preparation, and procedure (including blood loss, drains, organ injury, intraoperative complications). Clinically significant infection requiring systemic antibiotics (7-day hospital and 30-day follow-up) was identified in 0% of ceftizoxime, 15% of metronidazole-gentamicin, and 26% of cefoxitin receiving patients (p = 0.005). Mean ASEPSIS scores for each group were 2.3 (range 0-15) for ceftizoxime, 9.2 (range 0-45) for metronidazole-gentamicin, and 10.4 (range 0-75) for cefoxitin (p = 0.01). Ceftizoxime patients tended to have a shorter total hospital stay (12.2 days versus 19.7 days for cefoxitin versus 13.9 days for metronidazole-gentamicin; p = 0.04), although the procedure to discharge interval was not significantly different (p = 0.09). There was no difference in clinical outcome according to risk status. Anaerobic bacteria were observed more commonly in the ceftizoxime and cefoxitin groups, whereas enteric Gram-negative aerobes were observed most often in the metronidazole-gentamicin group. The study regimens were generally well tolerated. Drug costs were equivalent between ceftizoxime and cefoxitin and lowest with the metronidazole-gentamicin regimen. Ceftizoxime appears to be more effective for the prevention of infection in colorectal surgery than either cefoxitin or metronidazole-gentamicin in the dosage regimens studied.

Evaluation of the use of cefuroxime and cefuroxime axetil in an intravenous-oral stepdown program.

OBJECTIVE: To characterize cefuroxime and cefuroxime axetil use under the influence of a parenteral-to-oral (iv-po) stepdown program. DESIGN: Open single-center retrospective review. SETTING: Tertiary care teaching and referral Canadian hospital with 1100 beds. PATIENTS: A random sample of 78 patients receiving cefuroxime was compared with a random sample of 50 patients receiving iv-po cefuroxime stepdown. RESULTS: During the first 6 months following formulary introduction, 1535 patients received cefuroxime. Stepdown to any oral antibiotic occurred in 22% of patients. Cefuroxime axetil was used as the stepdown agent in 64% of these cases. In a comparison of nonstepdown courses with stepdown courses, some differences were apparent. Nonstepdown treatment courses were primarily prophylactic, whereas stepdown courses were typically initiated as primary therapy for the 10-day management of respiratory tract infections (p < 0.001). Conversion to oral therapy typically occurred on day 5 of parenteral therapy and continued for 5 days. Stepdown was considered possible in 46% of treatment courses in which this process did not happen. When stepdown did occur, it was considered timely in 64% of cases, unnecessarily delayed in 32%, and premature in 4% of treatment courses. Stepdown did not appear to be associated with a negative impact on patient outcome. Mean +/- SD cost of drug therapy per day was less for the stepdown group (US $15.78 +/- $5.97) than the nonstepdown group (US $25.47 +/- $7.87; p < 0.001). CONCLUSIONS: As a result of this study we intend to maintain cefuroxime and cefuroxime axetil on the formulary and continue to judiciously promote the timely conversion to oral therapy.

Double-blind comparison of cefazolin and ceftizoxime for prophylaxis against infections following elective biliary tract surgery.

Antibiotics have been shown to reduce the incidence of wound infections after elective biliary tract procedures. Cefazolin and cefoxitin are among the agents most commonly promoted for this purpose. Cefoxitin has been substituted with ceftizoxime in many institutions; however, the role of ceftizoxime as a prophylactic agent in this setting has not been determined. To assess the comparative prophylactic efficacies of cefazolin and ceftizoxime in biliary tract surgery, we conducted a double-blind, randomized prospective clinical trial in a tertiary-care teaching hospital. Adult patients were randomized to one of two treatment groups and received a 30-min preoperative dose of study drug and as many as two postoperative doses at 12 and 24 h, depending on hospitalization status. Cefazolin and ceftizoxime were given as 1,000-mg doses. Patients with infections, those receiving prior antibiotics, or those with beta-lactam allergies were excluded. Over the 19-month study tenure, 167 patients were enrolled. Seventeen patients were excluded from analysis because of protocol violations. Of the 150 evaluable patients (72 and 78 receiving cefazolin and ceftizoxime doses, respectively), there was no significant difference among groups regarding sex, age, weight, preoperative Apache II score, baseline chemistry, and hematological parameters. Groups were also equivalent regarding the surgeon, type of procedure, characteristics (blood loss, drains, organ injury, and complications), and duration of hospital stay (mean, 5.6 versus 4.3 days [P = 0.31]). No clinical evidence of infection (7-day hospital stay and 30-day follow-up) was identified in 93% of cefazolin and 92% of ceftizoxime patients (P = 1.0). Microbiological confirmation was found in only 18% of primary-site infections. In conclusion, cefazolin and ceftizoxime appear to be equivalent for the prevention of infection in biliary tract surgery with the dosage regimens studied.