Single pharmacy governed denosumab home administration: optimal adherence by means of a fracture liaison service (FLS) and home care collaboration.

Low adherence for denosumab (Dmab, Prolia®) is of major concern. Dutch pharmacies deliveries were calculated recently being 76.5% for a total of 3 injections. INTRODUCTION: Comparing a model where the prescriber maintains responsibility for adherence (model HC1) (Dmab is purchased and dispensed by patient's own community pharmacy and administered through a home care service (HC)) or an all-in-one model where the pharmacist maintains responsibility for the adherence (Dmab is purchased, dispensed, and administered by a pharmacist's HC) (HC2). METHODS: We counted the number of Dmab injections, follow-up appointments on time, Dmab administrations delayed to a maximum of 60 days, the number of Dmab discontinuations, and all causes legally traceable under EU privacy act (EDPR). RESULTS: Home care started by 2014 (study closure in 2021) and included 711 Dmab injections to 256 unique patients: HC1: 536 and HC2: 175 orders. The whole group received on average 2.8 Dmab injections by consistent intervals of about 182 days. Average administration after the latest Dmab injection: 272.8 days (HC1: 362.0 and HC2: 124.0 days). Administration of a subsequent injection > 60 days occurred in 26.6% (HC1: 38.8% and HC2: 6.2%; OR = 9.49). After adjustment for no more than three Dmab injections administered per patient, it occurred in 27.3% (HC1: 51.8% and HC2 4.4%; OR = 23.34). CONCLUSION: It was possible to achieve 94% adherence for Dmab injections treatment just by transferring the complete supply chain to one pharmacy-initiated home care provider after treatment initiation by either a physician or FLS health care professional.

Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma.

BACKGROUND: Hodgkin Lymphoma (HL) is highly curable when treated accurately. The challenge is to cure patients with the minimal risk of long-term complications. For that, optimal initial diagnostics are required to determine the optimal treatment plan. We offer non-academic hospitals in our Regional Comprehensive Cancer Centre network a centralised review of all diagnostic procedures from patients with newly diagnosed HL. We report our experience on concordances and discrepancies between local findings and central review results. PATIENTS AND METHODS: A haematologist and radiation oncologist at the Hodgkin Radboud University Nijmegen Medical Centre outpatient clinic examined all patients with newly diagnosed HL between February 2006 and May 2010. In a multidisciplinary lymphoma conference, diagnostic information is reviewed and treatment advice formulated. Discordant findings in pathology, staging and therapy were recorded as 'minor', no therapeutic consequences or 'major', adapted therapy advice. RESULTS: Altogether, 125 patients were included. Pathology review showed 86% concordance, with 4% major discordance, mainly nodular lymphocyte predominant sub-type. Revision of initial staging was concordant in 77%; however 15% major discordance of which most were upstaged. This resulted in 19% treatment adaption. CONCLUSION: Our findings highlight the discrepancies in interpretation of diagnostic tests. We advocate centralised review process for all newly diagnosed patients with HL.

Determination of 13C and 15N enrichments of urea in plasma by gas chromatography-combustion isotope ratio mass spectrometry and gas chromatography-mass spectrometry using the 2-methoxypyrimidine derivative.

We describe a GC-MS and GC-c-IRMS method for the determination of labeled urea tracer enrichments in plasma as a result of combined 13C- and 15N(2)-urea infusion experiments in piglets. Urea was converted into 2-methoxypyrimidine, a stable derivative, suited for analyses by both GC-MS and GC-c-IRMS. Using calibration curves for the respective working ranges (13C-urea: 0-1% APE; 15N(2)-urea: 0-7% MPE) enrichments were established in single point measurements; for 15N(2)-urea as values+/-0.15% MPE (95% confidence interval); for 13C-urea as values+/-0.02% APE (95% confidence interval). 15N(1)-urea enrichments were determined by measurement of the same sample with GC-c-IRMS and GC-MS. Subtraction of the 13C specific GC-c-IRMS data from the nondiscriminating GC-MS data for the sum of 13C- and 15N(1)-urea resulted in 15N(1)-urea enrichments+/-0.15% MPE (95% confidence interval). Application of the method in a combined 13C-urea bolus and 15N(2)-urea primed constant infusion experiment in piglet was demonstrated.

The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921).

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.

Chemotherapy only compared to chemotherapy followed by transplantation in high risk myelodysplastic syndrome and secondary acute myeloid leukemia; two parallel studies adjusted for various prognostic factors.

Comparisons of the effectiveness of chemotherapy and transplantation in AML in first complete remission (CR) have focused almost exclusively on patients with de novo disease. Here we used Cox modelling to compare these strategies in patients with MDS and s-AML treated by the Leukemia Group of the EORTC or at the MD Anderson Cancer Center. All patients were aged 15-60. The 184 EORTC patients received conventional dose ara-C + idarubicin + etoposide for remission induction, and after one consolidation course, were scheduled to receive an allograft, or an autograft if a sibling donor was unavailable. The 215 MDA patients received various high-dose ara-C containing induction regimens, and in CR, continued to receive these regimens at reduced dose for 6-12 months. CR rates were 54% EORTC and 63% MDA (P = 0.09). Sixty-five of the 100 EORTC patients who entered CR received a transplant in first CR. Disease-free survival in patients achieving CR was superior in the EORTC cohort, the 4-years DFS rates were 28.9% (s.e. = 4.8%) EORTC vs 17.3% (s.e. = 3.7%) MDA (P = 0.017). Survival from CR was not significantly different in the EORTC and MDA groups, as was survival from start of treatment. After accounting for prognostic factors the conclusions were unchanged. Despite various problems with the analysis discussed below, the data suggest that neither transplantation nor chemotherapy, as currently practised, can be unequivocally recommended for these patients in first CR and that questions as to the superior modality may be less important than the need to improve results with both.

Intensive treatment strategies in patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia.

Stem cell transplantation may lead to prolonged disease-free survival in young patients with high-risk myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia. About one-third of patients transplanted with an HLA-identical family donor will experience long-term disease-free survival. Outcome appears to be better for younger patients, patients with less advanced stages of MDS and treatment early in the course of the disease. The results of transplantation using partially matched family donors and phenotypically matched voluntary unrelated donors are still unsatisfactory, mainly due to significantly higher transplantation related mortality rate. For patients lacking a suitable sibling donor autologous stem cell transplantation may constitute an alternative. The presence of sufficient residual polyclonal stem cells and achieving a complete remission after chemotherapy forms a prerequisite for a successful transplantation. Further development of accurate prognostic classification systems will allow a risk-adapted strategy for an individual patient.

A case of tizanidine-induced hepatic injury.

The case history is presented of a woman who developed serious liver injury while taking 36 mg tizanidine daily. Other causes of hepatic injury were excluded. Symptoms resolved after discontinuation of tizanidine, and the liver enzyme levels were nearly normal 6 weeks after discontinuation of the drug. Rechallenge with 4 mg tizanidine caused a relapse. The temporal relationship between the symptoms and liver enzyme elevations, the absence of other potential causes, and the reaction to rechallenge, strongly implicate tizanidine as the cause of hepatic injury. As we are not aware of similar case histories, this seems to be the first reported case of tizanidine-induced hepatic injury.

Drug-utilization study on Curaçao.

The drug use on Curaçao was evaluated with the help of the prescription forms of twelve community pharmacies at Curaçao over a period of three months. The emphasis of the study was on three therapeutic groups: the systemic antibiotics, the psycholeptics and the anti-inflammatory and antirheumatic drugs. Within the group of systemic antibiotics broad-spectrum antibiotics were very frequently prescribed compared with the small-spectrum penicillins. The consumption of psycholeptics, particularly benzodiazepines, on Curaçao is remarkably low in comparison with drug utilization data of Denmark and the Netherlands. In contrast, the number of defined daily doses per 1,000 persons per day of antirheumatic drugs is higher compared with data from these two countries. Within the analysed groups, large differences occur between the two most important kinds of insurance, i.c., the poor people (PP) and social insurance bank (SVB) insurance. The PP-insured patients consume in the case of antibiotics and antirheumatic drugs almost twice as many and in the case of psycholeptics even five times as many as the SVB-insured patients do. A few calculations of prices prove that the extra amount of drugs consumed by PP-insured has important financial consequences.