Old tracer for a new purpose: potential role for 99mTc-2-Methoxyisobutylisonitrile (99mTc-MIBI) in renal transplant care.

AIM: Calcineurin inhibitors are substrates for P-glycoprotein (P-gp), the expression of which is associated with ABCB1 C3435T polymorphism. Individual P-gp response to calcineurin inhibitor may be linked to nephrotoxicity or rejection. Tc-2-Methoxyisobutylisonitrile (Tc-MIBI) is also a P-gp substrate. The aim of this study, therefore, was to determine Tc-MIBI organ kinetics and compare them with ABCB1 genotype with a view to replacing Tc-mercaptoacetyltriglycine (Tc-MAG3) with Tc-MIBI in renal transplant care. METHODS: Thirty prospective donors (13 male) were imaged for 20 min after administration of Tc-MIBI (400 MBq) intravenously. Posterior images of the abdomen were acquired at 30 and 120 min. Organ 30 min/peak count rate ratios and exponential two-point (30-120 min) rate constants (k, min) were calculated. Nineteen donors were genotyped for C3435T (exon 26), G2677T (exon 21), C1236T (exon 12), and G1199A (exon 11) ABCB1 polymorphisms using a PCR-based technique. RESULTS: Tc-MIBI and Tc-MAG3 gave similar perfusion images. Although their patterns of renal elimination were different, differential renal function was not significantly different. There was a negative trend between the hepatic 30 min/peak ratio and C3435T genotype (CC: 0.8374 ± 0.0502; TC: 0.6806 ± 0.1300; TT: 0.6919 ± 0.1506; P=0.083). Renal k showed a negative trend with C3435T (CC: 0.0021 ± 0.0020; TC: 0.0037 ± 0.0013; TT: 0.0040 ± 0.0012 min; P=0.087) but with no other genotypes. There were no significant sex-related differences in Tc-MIBI kinetics. CONCLUSION: Tc-MIBI can replace Tc-MAG3 for pretransplant workup. The ABCB1 C3435T polymorphism may influence Tc-MIBI kinetics and thus have a role in renal transplant care. Further prospective trials are required to establish the full potential of Tc-MIBI in renal transplant management.

Practice-centred evaluation and the privileging of care in health information technology evaluation.

UNLABELLED: Our contribution, drawn from our experience of the case study provided, is a protocol for practice-centred, participative evaluation of technology in the clinical setting that privileges care. In this context 'practice-centred' evaluation acts as a scalable, coordinating framework for evaluation that recognises health information technology supported care as an achievement that is contingent and ongoing. We argue that if complex programmes of technology-enabled service innovation are understood in terms of their contribution to patient care and supported by participative, capability-building evaluation methodologies, conditions are created for practitioners and patients to realise the potential of technologies and make substantive contributions to the evidence base underpinning health innovation programmes. BACKGROUND: Electronic Patient Records (EPRs) and telemedicine are positioned by policymakers as health information technologies that are integral to achieving improved clinical outcomes and efficiency savings. However, evaluating the extent to which these aims are met poses distinct evaluation challenges, particularly where clinical and cost outcomes form the sole focus of evaluation design. We propose that a practice-centred approach to evaluation - in which those whose day-to-day care practice is altered (or not) by the introduction of new technologies are placed at the centre of evaluation efforts - can complement and in some instances offer advantages over, outcome-centric evaluation models. METHODS: We carried out a regional programme of innovation in renal services where a participative approach was taken to the introduction of new technologies, including: a regional EPR system and a system to support video clinics. An 'action learning' approach was taken to procurement, pre-implementation planning, implementation, ongoing development and evaluation. Participants included clinicians, technology specialists, patients and external academic researchers. Whilst undergoing these activities we asked: how can a practice-centred approach be embedded into evaluation of health information technologies? DISCUSSION: Organising EPR and telemedicine evaluation around predetermined outcome measures alone can be impractical given the complex and contingent nature of such projects. It also limits the extent to which unforeseen outcomes and new capabilities are recognised. Such evaluations often fail to improve understanding of 'when' and 'under what conditions' technology-enabled service improvements are realised, and crucially, how such innovation improves care. SUMMARY: Our contribution, drawn from our experience of the case study provided, is a protocol for practice-centred, participative evaluation of technology in the clinical setting that privileges care. In this context 'practice-centred' evaluation acts as a scalable, coordinating framework for evaluation that recognises health information technology supported care as an achievement that is contingent and ongoing. We argue that if complex programmes of technology-enabled service innovation are understood in terms of their contribution to patient care and supported by participative, capability-building evaluation methodologies, conditions are created for practitioners and patients to realise the potential of technologies and make substantive contributions to the evidence base underpinning health innovation programmes.

A single center, pilot, double-blinded, randomized, comparative, prospective clinical study to evaluate improvements in the structure and function of facial skin with tazarotene 0.1% cream alone and in combination with GliSODin(®) Skin Nutrients Advanced Anti-Aging Formula.

BACKGROUND: Superoxide dismutase (SOD) reduces the reactive oxygen species formation associated with oxidative stress. An imbalance between free radicals and antioxidants can lead to accelerated aging. GliSODin(®) Skin Nutrients Advanced Anti-Aging Formula (GAAF) is an SOD-containing dietary nutricosmetic formulated with other nutraceuticals that promote improvements in the structure and function of the skin, including hydration, elasticity, structural integrity, and photoaging caused by oxidative stress. Tazarotene cream 0.1% (TAZ) is a United States Food and Drug Administration-approved drug indicated for use in the mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines when taken in conjunction with a comprehensive skin care and sun avoidance program. OBJECTIVE: To determine if the antioxidant, anti-aging, hydrating and skin-rejuvenating properties of GAAF complement the retinoic actions of TAZ to improve the structure and function of facial skin. METHOD: A 90-day comparative study of ten subjects with facial photodamage; daily topical application of TAZ was used in combination with three capsules of GAAF (780 mg each) or placebo orally, with food, per the randomization allocation. RESULTS: After 90 days of treatment, TAZ alone and in combination with GAAF improved fine wrinkles (↓1.2 versus 2.0), mottled hyperpigmentation (↓2.2 versus 2.8) and overall photodamage (↓1.0 versus 1.8), as well as patient-reported response to treatment (↓2.0 versus 1.6). At week 12, TAZ/GAAF combination treatment (Group A) versus TAZ treatment alone (Group C) was of significant clinical benefit, with respect to fine wrinkling (14.7%/41.7%), overall photodamage (15.6%/53.0%), skin moisture (19.1%/103.2%), skin elasticity (12.8%/87.7%), and response to treatment (8.8%/21.4%). CONCLUSION: The study suggests GAAF in combination with TAZ is safe and provides significant clinical benefit with relative improvement in facial fine wrinkling, overall photodamage, skin moisture and elasticity.

Renal and hepatic kinetics of Tc-99m-labelled hexakis-methoxy-isobutyl Isonitrile.

OBJECTIVE: Technetium-99m-labelled hexakis-methoxy-isobutyl isonitrile (Tc-99m-MIBI) is a substrate for P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter protein, and can be used to image P-gp expression. The aim was to study normal kinetics of Tc-99m-MIBI in the kidney and liver to help understand physiological studies of P-gp expression in these organs. METHODS: Thirty healthy kidney transplant donors received intravenous Tc-99m-MIBI followed by dynamic scintigraphy for 20 min and static imaging at 30 and 120 min. Time-activity curves were generated from parenchymal ROI. An assumed mono-exponential Tc-99m-MIBI blood clearance with rate constant of 0.3 min-1 was used to predict the Tc-99m- MIBI that would have accumulated in the organs had none left. The activities leaving were then calculated by subtraction and expressed as percentages of the predicted total accumulated activities. RESULTS: Kidney time-activity curves peaked at 2-4 min then declined to a plateau from ~15-16 min equal to 31 [SD 5]% of the total activity accumulated (corresponding to 69 [5]% rapidly eliminated) (phase 1). Bladder activity followed a similar but opposite time course. Between 30 and 120 min (phase 2), activity left at 0.36 (0.13) %.min-1. Liver curves peaked at 8-10 min. Differentiation of the elimination curve revealed that a variable proportion of tracer (5-56%; mean 30 [14]%) was rapidly excreted over ~11 min. From 30 min, activity left at 1.02 (0.23) %.min-1. There was no correlation between renal and hepatic elimination rates in either phase or between early and late phase elimination rates in either organ. CONCLUSIONS: Early renal elimination is predominantly via glomerular filtration and urinary excretion. The liver rapidly excretes a more variable and lower proportion of Tc-99m-MIBI than the kidney. P-gp located at the urine/tubule and bile/hepatocyte boundaries prevents Tc-99m-MIBI re-entering cells and thereby influences elimination and retention in both phases, although other ABC transporters are probably also involved.

Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. OBJECTIVE: The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. METHODS: An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered). Medical savings were calculated as costs saved due to relapses avoided and prevention in disability progression steps. In the base case analysis, we assumed 89.4% persistence, a cost per relapse of $4,682, and a cost per disability progression step of $1,788. Monthly cost of therapy was defined as wholesale acquisition cost ($0 contractual discounts and $25 patient copayment assumed in the base case analysis) plus routine monitoring costs as assessed by an expert panel. The primary economic endpoint was cost per relapse avoided. Costs and outcomes occurring in the second year were discounted 3% to bring to 2008 present values. Oneway and multiway probabilistic (Monte Carlo) sensitivity analyses were conducted on key input variables to assess their impact on cost per relapse avoided. RESULTS: Without DMD treatment, patients were predicted to experience 2.55 relapses and 0.44 disability progression steps over a 2-year period (discounted values). The 2-year reductions in clinical relapses for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.66, 0.42, 0.74, and 0.70, respectively. The 2-year reductions in disability progression steps for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.05, 0.15, 0.12, and 0.11, respectively. In the base case analysis, IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate had the most favorable costs per relapse avoided ($80,589; $87,061; and $88,310; respectively) and IFN Beta-1a IM injection had the least favorable cost-effectiveness ratio ($141,721 per relapse avoided). Sensitivity analyses showed that these results were robust to changes in key input parameters, such as the number of relapses and disease progression steps in untreated patients, the RRR in clinical relapse and progression rates, the rate of persistence, the average cost of relapse, and the average cost of a disease progression step. CONCLUSION: This evaluation suggests that IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate represent the most cost-effective DMDs for the treatment of RRMS, where cost-effectiveness is defined as cost per relapse avoided, assuming that (a) the RRR in relapses and disease progression steps calculated from multiple DMD placebo-controlled clinical trials reflect real differences among DMDs over 2 years; and (b) resource unit costs derived from published sources reflect economic consequences of relapses and disease progression.

Current management of glaucoma and the need for complete therapy.

Glaucoma is a long-term ocular neuropathy defined by optic disc or retinal nerve fiber structural abnormalities and visual field abnormality. Primary open-angle glaucoma is the most common type of glaucoma. Currently available treatments, initiated in a stepwise process, focus on intraocular pressure (IOP) reduction, and initially include topical drug therapy (single then multidrug combinations), followed by laser then surgical treatment. Topical prostaglandin analogues or beta-adrenergic receptor blockers are first used, followed by alpha-agonists or topical carbonic anhydrase inhibitors, and infrequently, cholinergic agonists and oral therapy. Limitations to existing topical IOP-reducing medications include continued disease progression in glaucoma patients with normal IOP, treatment failure, and low rates of compliance and persistence. Therapeutic agents under investigation include neuroprotectants, which target the disease process manifested by death of retinal ganglion cells, axonal loss, and irreversible loss of vision. Neuroprotectants may be used alone or in combination with IOPreducing therapy (a treatment strategy called complete therapy). Memantine, an N-methyl-D-aspartate receptor blocker currently approved for dementia, is the neuroprotectant farthest along in the process seeking regulatory approval for glaucoma treatment and has a favorable safety profile because of its selective mechanism of action. Several other neuroprotectants are in early stage investigation. Complete therapy provides hope for improved outcomes by reducing the significant morbidity and economic consequences that occur as a result of neurodegeneration and disease progression.

Safety and tolerability of concurrent natalizumab treatment for patients with Crohn's disease not in remission while receiving infliximab.

BACKGROUND: Natalizumab, a humanized monoclonal IgG(4) antibody to alpha4 integrin, was investigated as a treatment of active Crohn's disease (CD). The safety of natalizumab given in combination with infliximab has not previously been studied. METHODS: Seventy-nine adult patients with active CD (Crohn's Disease Activity Index [CDAI] score > or = 150) despite ongoing infliximab treatment were randomized 2:1 to receive 3 intravenous infusions of natalizumab (300 mg; n = 52) or placebo (n = 27) every 4 weeks. Patients received infliximab (5 mg/kg) every 8 weeks for at least 10 weeks before randomization and throughout the study. The primary objective was to assess the short-term safety and tolerability of natalizumab in patients concurrently receiving infliximab. Secondary and tertiary objectives included measures of efficacy, health-related quality of life (HRQoL), and effects on inflammatory markers. A subset of patients also participated in a pharmacokinetic/pharmacodynamic (PK/PD) analysis of the effects of concurrent treatment. RESULTS: Incidence of adverse events (AEs) was similar in the treatment groups. AEs frequently reported in both groups were headache, CD exacerbation, nausea, and nasopharyngitis. No patient had a hypersensitivity-like reaction to natalizumab, whereas 4 patients (5%) experienced reactions to infliximab. Two patients (4%) developed anti-natalizumab antibodies; 10 patients (14%) developed anti-infliximab antibodies. The mean CDAI score decreased with natalizumab plus infliximab but was unchanged with infliximab alone (-37.7 versus +3.5; P = 0.084). Patients in both groups showed small increases in HRQoL (P = 0.811). No drug-drug interactions were noted. CONCLUSIONS: The combination of natalizumab plus infliximab was well tolerated. Several positive trends suggested that treating patients not in remission with infliximab plus natalizumab had greater efficacy than treatment with infliximab alone.

Multidrug resistance gene-1 (MDR-1) haplotypes have a minor influence on tacrolimus dose requirements.

P-glycoprotein (P-gp) and the drug metabolizing enzymes have major pharmacokinetic effects. Variability in tacrolimus absorption is influenced by P-gp activity which, in turn, is affected by single nucleotide polymorphisms (SNPs) within the multidrug resistance-1 gene (MDR-1). Tacrolimus dose requirements of 206 stable renal transplant patients were related to MDR-1 genotypes of SNPs C1236T, G2677T/A and C3435T, as well as haplotypes: C-G-C and T-T-T. Lower dose-normalized blood tacrolimus concentrations were achieved for: 2677-GG genotype patients, as compared to 2677-TT, and for 3435-CC patients as compared to 3435-TT patients. There was a small, but significant, difference in dose requirements between haplotypes C-G-C and T-T-T patients, which was not significant when patients were subclassified as producers and non-producers of cytochrome P450 3A5 (CYP3A5). The activities of CYP3A5 and P-gp have been shown to influence bioavailability of several drugs. Our data suggest that MDR-1 haplotypes have a relatively minor association with tacrolimus pharmacokinetics.

Cost considerations in the medical management of glaucoma in the US: estimated yearly costs and cost effectiveness of bimatoprost compared with other medications.

INTRODUCTION: The aim of this study was to evaluate the cost effectiveness of glaucoma treatment with bimatoprost compared with other intraocular pressure (IOP)-lowering medications in adult patients with chronic glaucoma or ocular hypertension (IOP of between 22 mm Hg and 34 mm Hg), from a US healthcare payers' perspective. METHODS: Estimated yearly costs and cost per treatment success for 0.03% bimatoprost once daily (Lumigan) were compared with 0.5% timolol twice daily (generic), 0.005% latanoprost once daily (Xalatan) and the fixed combination of 0.5% timolol and 2.0% dorzolamide twice daily (Cosopt). The model was based on year 2003 medical resource costs (physician visits and drug acquisition costs) and treatment success rates from published clinical trials. The clinical measure utilised was the percentage of patients achieving target IOPs. RESULTS: A higher percentage of patients achieved target IOPs with bimatoprost than with each of the other medications. At most target pressures, the cost per treatment success for patients starting treatment on bimatoprost was less than that for patients started on other drugs. This was true despite that, when looking at costs alone, the estimated yearly costs for bimatoprost (averaged over both patient success and patient failures) were similar to or greater than those for the other drugs. The greatest differences in cost per treatment success were seen at target pressures < or =15 mm Hg. For example, at a target pressure of 13 mm Hg, the cost per treatment success based on the model was 9238-10,229 US dollars for bimatoprost, 23,218 US dollars for timolol, 21,943 US dollars for latanoprost and 16,034 US dollars for timolol/dorzolamide. The incremental cost of achieving additional clinical success for bimatoprost ranged from 800 US dollars to 1,700 US dollars versus generic timolol, and from 300 US dollars to 3,100 US dollars versus timolol/dorzolamide. Bimatoprost was more effective and less costly than latanoprost. CONCLUSION: In our simplified model of cost per treatment success based on responder rates at varying IOPs, the greater efficacy of bimatoprost resulted in a cost per treatment success that was generally lower for bimatoprost than for timolol, latanoprost or timolol/dorzolamide. This was most pronounced at target pressures <15 mm Hg.

The cost of migraine and its treatment.

Migraine headache incurs estimated annual costs totaling as much as 17 billion dollars in the United States. Most of the direct costs are for outpatient services: medications, office or clinic visits, emergency department visits, laboratory and diagnostic services, and management of treatment side effects. Indirect costs from lost productivity in the workplace add substantially to the total. The triptan class of drugs, used for abortive treatment, account for the greatest portion of medication costs. Because these agents are expensive, optimal use is critical. Research suggests that a stratified care strategy, with initial therapy based on the patient's score on the Migraine Disability Assessment Scale, is both clinically advantageous and more cost-effective than stepped-care strategies. Also, the triptans are not interchangeable, and costs as well as clinical outcomes may vary with different agents in this class. Migraine prophylaxis is aimed at preventing frequent attacks and the development of a long-term condition that often incurs heavy costs for abortive treatment, diagnostic services, and medical care. Agents approved for migraine prophylaxis include the antiepileptics divalproex and topiramate and the beta blockers propranolol and timolol. As with abortive therapy, costs vary widely among these prophylactic agents. A novel approach to migraine prophylaxis is injection of botulinum toxin. A cost-analysis model is presented to show the impact of utilizing botulinum toxin in a large managed care system.

Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians.

Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5 and CYP3A5*3/*3 homozygotes do not. We now present results with direct typing of the CYP3A5 genotype for this group of 180 kidney-only transplant recipients from a single center. South Asian and white patients with at least one CYP3A5*1 allele achieved twofold lower dose-normalized tacrolimus blood concentrations compared with CYP3A5*3/*3 homozygotes, confirming our previous findings for the CYP3AP1 SNP. There was a significant delay in achieving target blood concentrations in those with at least one CYP3A5*1 allele. Determination of the CYP3A5*1/*3 genotype could be used to predict the tacrolimus dose requirement and, given incomplete linkage, would be better than determination of the CYP3AP1 genotype.

The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation.

Previously, we reported that, at 3 months after renal transplantation, individuals with CYP3AP1 genotype CYP3AP1*1 (linked to CYP3A5*1 and strongly associated with expression of CYP3A5) required twofold higher doses of tacrolimus to achieve target blood concentrations than individuals with the genotype CYP3AP1*3/*3 (CYP3A5 nonexpressors). This study assesses the relationship between concentration-controlled dosing during the early period after transplantation, the time to achieve target concentrations and genotype in 178 renal transplant recipients (CYP3AP1*1/*3 or *1/*1: n = 53, CYP3AP1*3/*3: n = 125). Patients with CYP3AP1*1/*3 or *1/*1 had lower mean tacrolimus concentrations during the first week (Median 13.5 vs. 18.5 microg/L, p < 0.0001) with significant delay in achieving target concentrations (15-20 microg/L during week 1, then 10-15 microg/L). More CYP3AP1*3/*3 patients had tacrolimus concentrations above target during the first week (73.6% vs. 35.8%, p = 0.003). There was no difference in the rate of biopsy-confirmed acute rejection, but rejection occurred earlier in the CYP3AP1*1/*3 or *1/*1 group (median 7 d vs. 13 d, p = 0.005). In conclusion, an initial dosing regimen for tacrolimus based on knowledge of the CYP3AP1 genotype and subsequently guided by concentration measurements has the potential to increase the proportion of patients achieving target blood concentrations early after transplantation.

Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome p4503A5 and P-glycoprotein correlate with dose requirement.

BACKGROUND: There is marked heterogeneity in blood concentrations of tacrolimus following standard body-weight-based dosing. This is most apparent in black patients, who have a higher dose requirement when compared with other ethnic groups. Differences in intestinal P-glycoprotein and hepatic and intestinal cytochrome P4503A activity have been postulated as contributing to this problem. METHODS: The dose-normalized blood concentrations of tacrolimus at 3 months after renal transplantation were related to CYP3AP1 and multiple drug resistance (MDR)-1 genotypes determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: We found that a single nucleotide polymorphism in the CYP3AP1 pseudogene (A/G(44)) that previously has been noted to be more common in African Americans and strongly associated with hepatic CYP3A5 activity correlated well with the tacrolimus dose requirement. A weaker association was found for a polymorphism in the MDR-1 gene, which influences intestinal P-glycoprotein expression. CONCLUSIONS: The CYP3AP1 genotype is a major factor in determining the dose requirement for tacrolimus, and genotyping may be of value in planning patient-specific drug dosing.

Treatment and outcome of peritonitis in automated peritoneal dialysis, using a once-daily cefazolin-based regimen.

OBJECTIVE: We determined the effectiveness of a once-daily cefazolin-based regimen in treating automated peritoneal dialysis (APD) peritonitis. DESIGN: We carried out a retrospective analysis of all APD peritonitis episodes treated with a once-daily cefazolin protocol. SETTING: The study was performed in a peritoneal dialysis unit in a tertiary care hospital. PATIENTS AND METHODS: We studied 60 episodes of primary peritonitis in 40 patients on APD. Each patient was treated with a vancomycin-free regimen consisting of intraperitoneal cefazolin (1.5 g IP) with gentamicin IP administered in the daytime exchange. The main outcome measures were successful treatment of peritonitis, removal of peritoneal catheter, relapse of peritonitis, and patient death. RESULTS: Gram-positive infections occurred in 35 episodes (58.3%), gram-negative Infections in 10 episodes (16.7%), culture-negative infections in 14 episodes (23.3%), and a yeast infection in 1 episode (1.7%). Of the 60 episodes, 47 (78.3%) were successfully treated. In 10 episodes (16.7%), catheters were removed (9 for treatment failure, 1 for yeast infection). Four patients (8%) had a relapse of infection within 4 weeks of completing antibiotic therapy. One patient (1.7%) died. CONCLUSIONS: Our results demonstrate that once-daily cefazolin with gentamicin IP is an effective treatment for APD peritonitis, with the advantage of being easy to administer and enabling patients to remain on APD during treatment.

Colchicine myoneuropathy in a renal transplant patient.

Colchicine is widely employed for the treatment of gout in renal transplant patients where NSAIDs are contra-indicated and allopurinol prophylaxis is often avoided due to concomitant azathioprine immunosuppression. We report here a case of colchicine-induced myoneuropathy in a renal transplant recipient. Our patient had myalgia, muscle weakness, elevated creatine kinase levels, myopathic changes on electromyography and peripheral neuropathy. Withdrawal of colchicine resulted in recovery within 4 weeks. Renal transplant recipients are likely to be at greater risk of colchicine-induced myoneuropathy due to the unique concurrence of risk factors predisposing to toxicity in such patients. These risk factors include the high incidence of gout in this population, widespread use of colchicine as first-line therapy, impaired renal function and concomitant cyclosporin treatment. The diagnosis should be considered in any renal transplant recipient receiving the drug who develops myopathy. Prompt withdrawal of colchicine therapy should result in rapid clinical and biochemical improvement.

Clinical guidelines for the treatment of glaucoma.

Several documents guide screening and detection of glaucoma. The AAO guidelines are considered the current standard. The VA has established the need for regular screening based on identified factors. Finally, a task force working with NCQA to develop a glaucoma-related HEDIS measure may provide future direction in populationwide care.

Constructing disease management programs for glaucoma.

Glaucoma, which is associated with diabetes, hypertension, and hypothyroidism, is considered to be a good candidate for disease management. This article explains to clinicians and administrators who are interested in the identification and treatment of glaucoma what they should know about disease management and how they might benefit from establishing a DM program for glaucoma.