Daniel T. Grima

Immunoglobulin free light chain levels and recovery from myeloma kidney on treatment with chemotherapy and high cut-off haemodialysis

BACKGROUND To determine the efficacy of immunoglobulin free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) as an adjuvant treatment to chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM). METHODS Sixty-seven patients with dialysis-dependent renal failure secondary to MM were treated with HCO-HD and chemotherapy. RESULTS The population was predominantly male (62.7%) with new presentation MM (75%) and did not have a history of chronic kidney disease (84%). The mean serum creatinine at presentation was 662 (SD = 349) μmol/L and of the 56.7% of patients who had a renal biopsy, 86.7% had cast nephropathy as the principal diagnosis. Eighty-five percent of patients were treated with a chemotherapy regime consisting of dexamethasone in combination with a novel agent (bortezomib or thalidomide). The median number of HCO-HD sessions was 11 (range 3-45), 97% received an extended dialysis regime. Seventy-six percent of the population had a sustained reduction in serum FLC concentrations by Day 12, of these 71% subsequently became independent of dialysis. In total, 63% of population became independent of dialysis. Factors which predicted independence of dialysis were the degree of FLC reduction at Days 12 (P = 0.002) and 21 (P = 0.005) and the time to initiating HCO-HD (P = 0.006). CONCLUSION The combination of extended HCO-HD and chemotherapy resulted in sustained reductions in serum FLC concentrations in the majority of patients and a high rate of independence of dialysis.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL

BackgroundThe use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves.MethodsWe developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL’s interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation.ResultsWe demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software.ConclusionsUse of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.

Modelling Cost Effectiveness of Insulin Glargine for the Treatment of Type 1 and 2 Diabetes in Canada

Background and objectiveIntensive insulin therapy improves glycosylated haemoglobin (HbA1C) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (HbA1C) of ≤7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower HbA1C levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given HbA1C level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target HbA1C levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control.MethodsA long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by HbA1C levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with HbA1C levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in

Cost Effectiveness of Multi-Therapy Treatment Strategies in the Prevention of Vertebral Fractures in Postmenopausal Women with Osteoporosis

Can (2005 values).ResultsThe NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (HbA1C >7%; lifetime difference

Cost-Effectiveness Analysis of Therapies for Chronic Kidney Disease Patients on Dialysis A Case for Excluding Dialysis Costs

Can1398 and

Lack of Increased Colonization with Vancomycin-Resistant Enterococci during Preferential Use of Vancomycin for Treatment during an Outbreak of Healthcare-Associated Clostridium difficile Infection

Can1992, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were

A modeled economic evaluation of sevelamer for treatment of hyperphosphatemia associated with chronic kidney disease among patients on dialysis in the United Kingdom

Can18 661 and

Intraocular pressure control and persistence on treatment in glaucoma and ocular hypertension

Can20 799, respectively, in type 1 diabetes and

An economic evaluation of rizatriptan in the treatment of migraine

Can8041 and

Modelled cost-effectiveness of high cut-off haemodialysis compared to standard haemodialysis in the management of myeloma kidney.

Can8618, respectively, in type 2 diabetes (discounted results).ConclusionsThe cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.