Technetium-99-labelled methylene diphosphonate uptake scans in patients with dialysis arthropathy

Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy.     

PPI use in patients commenced on clopidogrel: a retrospective cross‐sectional evaluation

Background/Aims: Antiplatelet therapy with aspirin and clopidogrel is an important component of the management of acute coronary syndrome, but it also increases the risk of bleeding. There are no formal guidelines about the use of a proton pump inhibitor (PPI) for gastroprotection in patients on clopidogrel. This study assessed how many patients in the Royal Darwin Hospital (RDH) and the Royal Hobart Hospital (RHH) prescribed clopidogrel and at risk of bleeding were co‐prescribed PPIs. Methods: We conducted a retrospective cohort study using a pharmacy database to select all patients commenced on clopidogrel in a 1‐year period. We identified all patients newly prescribed clopidogrel and determined the proportion that had a risk factor for bleeding and also received a PPI. We also assessed the effect of the use of PPIs on the number of reported bleeds. Results: The final study cohort consisted of 385 patients who had been newly prescribed clopidogrel. Of all patients discharged on clopidogrel, 95·6% (368/385) had ≥1 risk factor for bleeding. One hundred and twenty‐eight of these patients [128/368, (34·8%)] were discharged on a PPI. Patients on dual antiplatelet therapy with an additional risk factor for bleeding and not discharged on a PPI were more likely to develop a major bleed than patients on dual antiplatelet therapy without a risk factor for bleeding not discharged on a PPI (11·1% vs. 1·8%; P < 0·01). Patients on dual antiplatelet therapy with an additional risk factor for bleeding not discharged on a PPI had a higher probability (borderline significance) of major bleeding, compared with patients on dual antiplatelet therapy with an additional risk factor for bleeding discharged on a PPI [PPI: 1/60, (1·7%) vs. no PPI: 6/54, (11·1%); P = 0·05]. Conclusions: Our results indicate that PPIs may only lower the probability of major bleeding in patients treated with dual antiplatelet therapy, who possess additional risk factor(s) for bleeding.     

Drug costs developments after patent expiry of enalapril, fluoxetine and ranitidine

Background

In order to increase price competition, government regulations focus on controlling drug costs. Drug costs after patent expiry are an area of particular interest because the substitution of branded medication with generics represents an opportunity for lowering drug costs. However, drug costs may not decrease after patent expiry, because of a lack of price competition and different national pricing systems.

Aim

The aim of this study was to investigate the trends in the use of generics after patent expiry for enalapril, fluoxetine and ranitidine and the subsequent changes, if any, in the costs of these medications.

Methods

A drug-utilisation study was performed using data from a large sample of Dutch pharmacies. Both volumes (measured as defined daily doses [DDD] per 1000 population) as well as drug costs (calculated per DDD) prior to and after patent expiry were calculated. Costs per DDD were compared using trend-line analysis. In addition, the relative market shares of the different trade channels (branded, parallel imported and generic) were compared before and after patent expiry.

Results

The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine.

Conclusions

Despite relatively high reimbursement prices for generics in the Netherlands, this example from the Dutch pharmaceutical market demonstrates the benefit of generic substitution for containing pharmaceutical costs, which contrasts with concerns raised by the Dutch government.     

Thalidomide-associated thrombocytopenia

OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy. Melphalan and prednisolone were discontinued, and monotherapy with dexamethasone 40 mg for 12 days per month was started. The patient's hematologic condition deteriorated again after about one year; dexamethasone was discontinued, and treatment with oral thalidomide 200 mg/day was initiated. About 2 weeks after thalidomide administration, the woman developed disabling adverse effects (flu-like symptoms, swollen fingers, rash and hematoma on her legs, shortness of breath, dry mouth, multiple petechiae). Laboratory testing showed neutropenia (neutrophils 0.4 x 10(9)/L) and thrombocytopenia (platelets 58 x 10(9)/L). Thalidomide was promptly discontinued; within 3 weeks, the laboratory values returned to pretreatment levels (1.3 x 10(9)/L and 267 x 10(9)/L, respectively) and her symptoms disappeared. DISCUSSION: Thrombocytopenia is a rarely reported hematologic adverse consequence of thalidomide therapy. A recent report identified 5 patients who developed thrombocytopenia while undergoing monotherapy with thalidomide for MM. According to the Naranjo probability scale, thalidomide was classified as the probable cause of thrombocytopenia in our patient. CONCLUSIONS: Unlike other antineoplastic drugs, thalidomide is rarely reported to cause severe hematologic toxicity. We present this case to increase clinicians' awareness for the potential of thalidomide to adversely affect platelet counts, particularly because its effectiveness in MM will likely result in expansion of its clinical use.     

Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis

Vitamin D has been associated with a decreased risk of multiple sclerosis (MS). In this study, serum 1, 25-dihydroxyvitamin D (1, 25-(OH)2 vitD) and 25-hydroxyvitamin D (25-OH vitD), regulatory T cell percentages and naïve and memory T helper cell subsets were measured in 26 patients with multiple sclerosis, 21 who were not on treatment with disease modifying therapy. These studies showed an inverse correlation between 25-OH vitD levels and Treg cell percentages and a direct correlation between Treg cell percentages and 1, 25-(OH)2 vitD:25-OH vitD ratios. In addition, 25-OH vitD levels correlated directly and 1, 25-(OH)2 vitD:25-OH vitD ratios correlated inversely with CXCR3+ naïve T helper cell percentages and CXCR3+naïve:CXCR3+ memory T helper cell ratios. All together, these data demonstrate that vitamin D measurements can reflect measures of immune status among patients with MS.