Cost-Effectiveness Analysis for the Treatment of Hyperphosphatemia in Predialysis Patients: Calcium-Based versus Noncalcium-Based Phosphate Binders.

BACKGROUND: Hyperphosphatemia in chronic kidney disease (CKD) patients is often treated with calcium carbonate (CaCO3) despite the fact that CaCO3 is associated with increased calcium load and potentially increased cardiovascular risk. Alternative treatments with noncalcium-based phosphate binders do not increase the calcium load but are more costly. This study analyzes the cost-effectiveness of sevelamer versus CaCO3 for the treatment of hyperphosphatemia in stage III-V predialysis CKD patients in Malaysia. METHODS: A Markov decision model was adapted to simulate a hypothetical cohort of CKD patients requiring treatment for hyperphosphatemia. Survival was estimated by using efficacy data from the INDEPENDENT-CKD clinical trial. Cost data was obtained from Malaysian studies while health state utilities were derived from literature. Analysis was performed over lifetime duration from the perspective of the Ministry of Health Malaysia with 2013 as reference year. RESULTS: In the base case analysis, sevelamer treatment gained 6.37 life years (5.27 QALY) compared to 4.25 life years (3.54 QALY) with CaCO3. At 3% discount, lifetime costs were RM159,901 ($48,750) and RM77,139 ($23,518) on sevelamer and CaCO3, respectively. Incremental cost-effectiveness (ICER) of sevelamer versus CaCO3 was RM47,679 ($14,536) per QALY, which is less than the WHO threshold of three times GDP per capita (RM99,395) per QALY. Sensitivity analyses, both using scenario sensitivity analysis and probabilistic sensitivity analysis, showed the result to be robust. CONCLUSIONS: Our study finds that sevelamer is potentially cost-effective compared to CaCO3, for the treatment of hyperphosphatemia in predialysis CKD III-V. We propose that sevelamer should be an option in the treatment of Malaysian predialysis patients with hyperphosphatemia, particularly those with high calcium load.

Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) is a rare idiopathic non-caseating granulomatous condition. It is rarely described in otorhinolaryngology-related journals, although facial palsy, lip-swelling, and lingua plicata, are its most common presenting features. This classical triad however is not always present in MRS. Other forms of orofacial swelling exist. This paper describes a patient with a variant of MRS, treated by us with intra-lesional steroid injection. We also discuss the other differential diagnoses that may mimic MRS.

Involvement of calyculin A inhibitable protein phosphatases in the cyclic AMP signal transduction pathway of mouse corticotroph tumour (AtT20) cells.

1. The role of non-calcineurin protein phosphatases in the cyclic AMP signal transduction pathway was examined in mouse pituitary corticotroph tumour (AtT20) cells. 2. Blockers of protein phosphatases, calyculin A and okadaic acid, were applied in AtT20 cells depleted of rapidly mobilizable pools of intracellular calcium and activated by various cyclic AMP generating agonists. Inhibitors of cyclic nucleotide phosphodiesterases were present throughout. The accumulation of cyclic AMP was monitored by radioimmunoassay, phosphodiesterase activity in cell homogenates was measured by radiometric assay. 3. Neither calyculin A nor okadaic acid altered basal cyclic AMP levels but cyclic AMP formation induced by 41 amino acid residue corticotrophin releasing-factor (CRF) was strongly inhibited (up to 80%), 1-Norokadaone was inactive. Similar data were also obtained when isoprenaline or pituitary adenylate cyclase activating peptide1-38 were used as agonists. 4. Pertussis toxin did not modify the inhibition of CRF-induced cyclic AMP production by calyculin A. 5. Pretreatment with calyculin A completely prevented the stimulation of cyclic AMP formation by cholera toxin even in the presence of 0.5 mM isobutylmethylxanthine (IBMX) and 0.1 mM rolipram. Cholera toxin mediated ADP-ribosylation of the 45 K and 52 K molecular weight Gs alpha isoforms in membranes from calyculin A-pretreated cells was enhanced to 150-200% when compared with controls. 6. Cholera toxin-induced cyclic AMP was reduced by calyculin A within 10 min when calyculin A was applied after a 90 min pretreatment with cholera toxin. Under these conditions the effect of calyculin A could be blocked by the combination of 0.5 mM IBMX and 0.1 mM rolipram, but not by 0.5 mM IBMX alone. 7. Phosphodiesterase activity in AtT20 cell homogenates showed a significant, 2.7 fold increase after treatment with calyculin A. In control cells phosphodiesterase activity was blocked by 80% in the presence of IBMX (0.5 mM), or IBMX plus rolipram (0.1 mM). In calyculin A-treated cells phosphodiesterase activity was also strongly inhibited by IBMX, but because of the stimulating effect of calyculin A, the activity remaining was still 55% of that found in control homogenates. This activity was reduced to 5% of control by using IBMX and rolipram in combination. Assay of phosphodiesterase in Ca2+ free conditions showed that calyculin A markedly increases the activity of rolipram sensitive (type 4) phosphodiesterase. 8. Taken together, blockers of protein phosphatases (PPases) impaired signal transduction through Gs-mediated pathways and activated cyclic AMP degrading phosphodiesterase(s), indicating that PPases 1 and/or 2A are essential for agonist-mediated regulation of cyclic AMP levels in AtT20 cells, and are thus important in maintaining the secretory phenotype of the cells.