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Biomedical subjects

C A Marra

Publications and source records attributed to C A Marra.

At least 19 recordsLinked to original sources
PubMed2006

Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis.

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. However, the efficacy, tolerability and safety of combination interferon and ribavirin (IFN-RIB) or peginterferon and ribavirin (PEG-RIB) anti-viral therapies post-LT are uncertain. We performed a comprehensive search of major medical databases (1980-2005) and conference proceedings (1996-2005). The main outcome measure was sustained virological response (SVR, undetectable HCV RNA) at 6 months. Summary estimates were calculated using random-effects models. Twenty-seven IFN-RIB and 21 PEG-RIB studies were included. IFN-RIB was associated with a pooled SVR rate of 24% (95% CI, 20-27%), while PEG-RIB was associated with an SVR rate of 27% (23-31%). Pooled discontinuation rates were 24% (21-27%) with IFN-RIB and 26% (20-32%) with PEG-RIB. The pooled rate of acute graft rejection was 2% (1-3%) with IFN-RIB and 5% (3-7%) with PEG-RIB. IFN-RIB and PEG-RIB therapies in HCV infection post-LT were associated with similar but overall low SVR and were poorly tolerated. The rate of acute rejection was small. The therapeutic advantage of PEG-RIB therapy observed in non-transplant chronic HCV infection appears to be attenuated post-LT. Clinical trials are needed to evaluate reasons for this post-transplant therapeutic disadvantage and to find strategies to ameliorate them.

Antiviral Agents↗
PubMed2004

The impact of low family income on self-reported health outcomes in patients with rheumatoid arthritis within a publicly funded health-care environment.

OBJECTIVE: Self-rated health (SRH) is an independent, strong predictor of morbidity and mortality. Socio-economic status (SES) is strongly associated with SRH. This study investigated the relationship between SES and SRH outcomes in a sample of patients with rheumatoid arthritis (RA) in Canada. METHODS: Both generic preference-based [Health Utilities Index Mark 3 (HUI3) and Short Form 6D (SF-6D)] and non-preference-based [disease-specific (Rheumatoid Arthritis Quality of Life, RAQoL) and a functional status (Health Assessment Questionnaire, HAQ)] SRH questionnaires were administered to 313 RA patients. Both proximate (education and annual household income) and contextual (neighbourhood income, education and unemployment) measures of SES were captured. Ordinary least squares (OLS) regression was used to adjust for RA severity while assessing the relationship between SRH and SES measures. Two-stage least-squares (TSLS) regression was used to determine if there was an inter-relationship between SES and SRH measures. RESULTS: The sample was well distributed across RA severity and SES measures. Contextual and proximate measures of SES were poorly correlated. Lower levels of proximate SES measures (but not contextual) were associated with poorer SRH outcomes. The OLS regressions showed significant associations between the HUI3 and the SF-6D overall scores and the HAQ for self-reported income. The RAQoL did not differ significantly across SES. TSLS regression confirmed the finding that self-reported income was similarly associated with the SRH measures. CONCLUSIONS: Even in a country with universal access to health-care, the impact of a chronic disease such as RA on SRH is associated with self-reported income. The finding that preference-based measures vary with income independently of RA severity could bias economic evaluation.

Adult↗
PubMed2002

The restoring effect of trifluralin and benznidazole on the abnormal fatty-acid pattern induced by Trypanosoma cruzi in the liver microsomes of infected mice.

The fatty-acid composition of liver lipids from mice infected with Trypanosoma cruzi (clone H510C8C3) or uninfected mice was investigated. The infected animals were treated orally for 30 days, with trifluralin (TFL) or benznidazole (BNZ), each at 100mg/kg.day, or only with the peanut oil used as the drug vehicle. The uninfected mice were also given the peanut oil. The treatments were stopped 10 days before the animals were killed. The liver microsomal lipids of each mouse were isolated and then analysed by gas-liquid chromatography. In terms of the total lipids, untreated infection evoked a significant increase in saturated fatty acids and the members of the n-9 fatty-acid family, with a concomitant decrease in the polyenoates of the n-3 and n-6 fatty-acid series. Each lipid subclass was affected to a different extent, the phospholipids being affected most. All lipid fractions, apart from the cholesterol esters, showed a significant increase in the proportion of n-9 isomers. Infection also produced a marked increase in the absolute amounts of triacylglycerides, cholesterol and cholesterol esters in liver microsomal membranes. After BNZ or TFL treatment, the fatty-acid pattern of mice that had been infected was indistinguishable from that of the control mice. The possible role of desaturase activity in the alterations observed is discussed.

Animals↗
PubMed2001

The effectiveness and toxicity of cyclosporin A in rheumatoid arthritis: longitudinal analysis of a population-based registry.

OBJECTIVE: To determine factors associated with response or toxicity to cyclosporin A (CSA) in a population-based inception cohort with rheumatoid arthritis (RA). METHODS: Prospectively collected longitudinal measures including tender joint count (JC), duration of morning stiffness (MS), systolic and diastolic blood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using generalized estimating equations. Survival methods were used to estimate CSA continuation time and its determinants. RESULTS: Of 133 patients (75% female, median RA duration 13 years), 37 discontinued CSA because of ineffectiveness (19) or because of toxicity (18) including increased SCr in 10, hypertension in 4, infections in 3, and gingival hyperplasia in 1. Patients remained on CSA a median of 75 months (95% confidence interval [CI] 38-112). Those receiving concomitant methotrexate (MTX) were more than 4 times as likely to continue on CSA therapy (hazard ratio 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) and concomitant MTX therapy (RR 0.79, 95% CI 0.63-0.99); decreased MS was predicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% CI 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 micromole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 mm Hg, 95% CI 3.0-6.4). CONCLUSIONS: Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.

Adult↗
PubMed2001

Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers.

OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease. DATA SOURCES: A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references. STUDY SELECTION: Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery of death. DATA SYNTHESIS: Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to infinity to NNTH 33). CONCLUSIONS: PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.

Adult↗
PubMed2001

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.

Canada↗
PubMed2000

5-HT3 receptor antagonists vs traditional agents for the prophylaxis of postoperative nausea and vomiting.

PURPOSE: Numerous antiemetics have been studied for the prevention of postoperative nausea and vomiting (PONV) including traditional agents (metoclopramide, perphenazine, prochlorperazine, cyclizine and droperidol) and the 5-HT3 receptor antagonists (ondansetron, dolasetron, granisetron and tropisetron). The results have been divergent and inconsistent. The purpose of this quantitative systematic review was to evaluate the effectiveness of 5HT3 receptor antagonists compared to traditional antiemetics for the prevention of PONV METHODS: A systematic search of the English language literature using computerized MEDLINE, EMBASE, and Pre-MEDLINE databases from 1966 to October 1999 and a manual search of references from retrieved articles were performed. Individual efficacy and adverse effect data was extracted from each of the studies according to a predefined protocol. The summary odds ratios were calculated using the Dersimonian and Laird method under a random effects model. RESULTS: A total of 41 trials met our pre-defined inclusion criteria and were included in our analysis. Results in the 32 studies examining PONV indicated a 46% reduction in the odds of PONV in the 5-HT3-treated group (0.54 [95% CI 0.42-0.71], P < 0.001). Evaluation of PONV by traditional antiemetic agent demonstrated a 39% reduction compared with droperidol (0.61 [95% CI 0.42-0.89], P < 0.001) and a 56% reduction compared with metoclopramide (0.44 [95% CI 0.31-0.62], P < 0.001). Results in the 34 studies examining vomiting indicated a 38% reduction in the odds of vomiting in the 5-HT3-treated group (0.62 [95% CI 0.48-0.81], P < 0.001). CONCLUSIONS: The 5-HT3 receptor antagonists are superior to traditional antiemetic agents for the prevention of PONV and vomiting. The reduction in the odds of PONV and vomiting is significant in the overall analysis and the subgroup analyses comparing 5-HT3 receptor antagonists with droperidol and metoclopramide.

Antiemetics↗
PubMed2000

Calcium deficiency modifies polyunsaturated fatty acid metabolism in growing rats.

Fatty acid desaturase activities were determined in liver microsomes from calcium-deficient rats and compared to calcium-sufficient ones. The calcium-deprived diet (0.5 g/kg) administered for 60 d caused a 30% inhibition in the delta5 desaturase activity and a 45-55% decrease in delta6 and delta9, respectively, facts that cannot be attributed to a reduction in food intake. In vitro addition of calcium, ethyleneglycol-bis(Beta-aminoethyl ether)N,N-tetraacetic acid, and/or cytosol fractions from control or calcium-deficient rats to microsomes from both groups of animals indicates that the reduced desaturase capacities would be the consequence of an indirect effect of calcium deprivation. The present work shows that the reduced unsaturated fatty acid biosynthesis might be the result of modifications in the physicochemical properties of microsomal membranes. Such changes could also be derived from the inhibition of phospholipase A2 activity induced by calcium deficiency.

Acyl Coenzyme A↗
PubMed2000

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.

Adolescent↗
PubMed2000

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.

Administration, Oral↗
PubMed2000

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.

Adolescent↗
PubMed1999

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. METHODS 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.

Ambulatory Surgical Procedures↗
PubMed1999

Acyl-CoA synthetase activity in liver microsomes from calcium-deficient rats.

A study on the kinetic properties of the nonspecific acyl-coenzyme A (CoA) synthetase activity in liver microsomal vesicles from both normal and calcium-deficient Wistar rats was carried out. After a 65-d treatment, the calcium-deficient diet reflected a 75% increase in the synthetase activity with respect to control animals. The apparent Vm was significantly enhanced, while the Km remained unchanged. We also provided experimental evidence about various fatty acids of different carbon length and unsaturation which depressed the biosynthesis of palmitoyl-CoA following different behaviors in control or calcium-deprived liver microsomes. In addition, we studied in detail the inhibition reflected by stearic, alpha-linolenic, or arachidonic acids, in the biosynthesis of palmitoyl-CoA in microsomal suspensions either from control or hypocalcemic rats. In control microsomes, stearic acid produced a pure competitive effect, while the other fatty acids followed a mixed-type inhibition. The competitive effect of stearic acid was not observed in calcium-deprived microsomes. At the same time, a mixed-type inhibition produced by either alpha-linolenic or arachidonic acid was diminished in deprived microsomes due to an increase in the noncompetitive component (alphaKi). These changes observed in apparent kinetic constants (Km, Vm, Ki, and alphaKi), as determined by Lineweaver-Burks and Dixon plots, were attributed to the important alterations in the physicochemical properties of the endoplasmic reticulum membranes induced by the calcium-deficient diet. The solubilization of the enzyme activity from both types of microsomes demonstrated that the kinetic behavior of the enzyme depends on the microenvironment in the membrane, and that the calcium ion plays a crucial role in determining the alterations observed.

Animals↗
PubMed1999

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.

Adult↗
PubMed1999

Systematic review of the treatment of early Lyme disease.

Lyme disease is a rapidly emerging infectious disease and there are still many unanswered questions with respect to appropriate laboratory tests required for diagnosis of early Lyme disease, types of antimicrobials required for treatment and duration of therapy. A qualitative systematic review was used to summarise the existing data for the treatment of early Lyme disease. Eleven antibacterial therapy trials and 3 cost-effectiveness analyses met the inclusion criteria for this review. Antibacterial regimens that have been studied include phenoxymethylpenicillin (penicillin V), amoxicillin, amoxicillin/probenecid, tetracycline, doxycycline, cefuroxime axetil, erythromycin, roxithromycin, azithromycin and ceftriaxone. The data support the use of oral beta-lactam antibacterials [phenoxymethylpenicillin (penicillin V), amoxicillin, cefuroxime axetil] and oral tetracyclines as effective first-line treatment modalities for early Lyme disease. Oral macrolides are considered second-line agents as their clinical efficacy has been less than that of the beta-lactams and tetracyclines. Courses of therapy ranging from 10 to 21 days are supported by the available evidence, although the optimal duration of therapy is unknown.

Anti-Bacterial Agents↗
PubMed1999

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.

Acute Disease↗
PubMed1999

Effect of calcium deficiency on acyl-CoA synthetase activity in microsomes from various rat tissues.

The specific activity of long-chain acyl-CoA synthetase in microsomes from various tissues of control and calcium-deficient rats was determined. It was found that the saturated acids, palmitic and stearic, were preferential substrates compared to the non-saturated linoleic, alpha-linolenic and eicosa-8,11,14-trienoic acids. All of them showed similar Vm values with different affinity constants. After 60-day treatment on a calcium-deficient diet (0.5 g Ca/Kg diet), a significant increase in the acyl-CoA synthetase activity was observed for all the tested fatty acids in liver and kidney microsomes. These changes were evoked without any modification in the substrate selectivities shown for the control microsomes, and they were well-correlated with calcium level in both tissues. Under the calcium deficient state an increase in Vm values was observed for palmitic and eicosatrienoic acids with no changes in the corresponding Km, suggesting an increment in the number of active enzyme molecules within the microsomal membrane.

Animals↗