van Eric Roon

A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300–600 mg/day versus benzbromarone 100–200 mg/day in patients with gout

Objectives: To compare the efficacy and tolerability of allopurinol 300–600 mg/day versus benzbromarone 100–200 mg/day used to attain a target serum urate concentration (sUr) ⩽0.30 mmol/l (5 mg/dl). Methods: A randomised, controlled, open-label, multicentre trial in gout patients with renal function defined as a calculated creatinine clearance ⩾50 ml/min. Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If sUr ⩽0.30 mmol/l was not attained after 2 months, the dose was doubled to allopurinol 300 mg twice a day or benzbromarone 200 mg once a day (stage 2). The primary end point was treatment success in either of the two stages, defined as clinical tolerability and attainment of biochemical target sUr. Results: Sixty-five patients were enrolled in stage 1; 36 received allopurinol and 29 received benzbromarone. Fifty-five patients (85%) were analysed at stage 1: the success rates were 8/31 (26%) and 13/25 (52%), respectively, and the difference was −0.26 (95% CI from −0.486 to −0.005), p = 0.049. At stage 2, the success rates were 21/27 (78%) and 18/23 (78%), respectively, and the difference was −0.005 (95% CI from −0.223 to 0.220), p = 1.00. Two patients stopped receiving allopurinol and three stopped receiving benzbromarone because of adverse drug reactions. Conclusions: Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/day according to the target sUr produced significantly higher success rates (both 78% successful in attaining sUr ⩽0.30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation. Trial registration number: ISRCTN49563848).

A before-after study of multi-resistance and cost of selective decontamination of the digestive tract

Abstract.Background:We compared standard antibiotic use with an antibiotic policy based on selective decontamination of the digestive tract (SDD) for cost and microbiology.Patients and Methods:A 2-year before-after observational study was performed in an 11-bed, mixed medical and surgical intensive care unit (ICU). We included all consecutive patients admitted to the ICU 1 year before and 1 year after institution of SDD (patients admitted within the 2-month SDD run-in period were excluded from analysis). In the year before SDD, 513 patients were treated in the ICU (mean APACHE II 19.5), compared to 529 in the year with SDD (mean APACHE II 19.4).Results:The duration of mechanical ventilation was shorter in the SDD-treated patients (median 3, interquartile range [IQR] 2–7 days vs median 4 days, IQR 2–10, p = 0.03). The total of ICU variable costs, microbiological costs and antibiotic costs were equal in both episodes: €1,171 versus €1,168 per patient). Aerobic gram-negative bacilli (AGNB) and multiresistant AGNB were found less frequently in SDD-treated patients, RR 0.37 (95% CI 0.33–0.42) and RR 0.28 (95% CI 0.19–0.42). Multi-resistant AGNB in tracheal secretions and urine more than 72 hours after admission were completely absent in SDD-treated patients.Conclusion:The overall cost per patient treated during an antibiotic policy including SDD was equal to a policy supporting standard antibiotic care. In addition, duration of ventilation decreased and a trend was shown towards a decreased length of ICU and hospital stay. Less frequently, cultures from organ sites containing AGNB were found during SDD and the number of multi-resistant strains was significantly reduced at organ sites, in particular trachea and urine. Fewer patients were colonized with multi-resistant AGNB but these numbers did not reach statistical significance.

Safety of citrate based hemofiltration in critically ill patients at high risk for bleeding: a comparison with nadroparin.

Purpose To study the incidence and severity of bleeding in high risk critically ill patients during high volume, citrate based continuous veno-venous hemofiltration (CVVH). Design A prospective 1-year observational cohort study comparing citrate based CVVH with nadroparin based CVVH. Procedures Critically ill patients with multiple organ dysfunction and in need of CVVH were observed for bleeding complications during their CVVH sessions. Pre-defined criteria determined that patients were treated with citrate based CVVH in case of active bleeding or increased risk for bleeding. Otherwise nadroparin was used as anticoagulant. Statistical and Outcome Methods The incidence of bleeding complications, the number of transfused blood cell concentrates and the filter-run-time were recorded. Analyses were made by non-parametric tests. Main Findings Fifty-five patients received 272 CVVH sessions. In the citrate group 14.8% experienced a bleeding complication compared to 25% in the nadroparin group (p=0.04). The number of transfused red blood cell concentrates was not different between groups. The nadroparin group had a longer filter run time (median 31.5 hours versus 22.5 hours, p=0.0001). Conclusions In high risk critically ill patients citrate based anticoagulation for CVVH is safe in terms of bleeding complications and transfusion requirements.

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: a case report

A case of a serious poisoning with the calcium entry blocker amlodipine is described, which was treated effectively with 4‐aminopyridine. Calcium is suggested as general treatment of poisoning with calcium entry blockers in many guidelines. The use of intravenous 4‐aminopyridine is theoretically useful to treat poisoning from calcium entry blockers and was demonstrated in this case report.

Systematic review of trends in prophylaxis of corticosteroid-induced osteoporosis: the need for standard audit guidelines

SummaryCorticosteroid-induced osteoporosis (CIOP) is currently undertreated. Systematic review of the literature revealed that the percentage of patients treated adequately is dependent on study quality. Therefore, it remains unknown whether adherence to the guidelines is really so poor. Five major quality criteria provide the standard for future studies on this scope.IntroductionIt has recently been stated that the degree of prophylaxis of corticosteroid-induced osteoporosis (CIOP) is low and effort should be put into determining reasons for non-prescribing of preventive agents. The aim of this study was to identify: how many studies adequately audit the prevalent guideline; the longitudinal trends in prevention of CIOP; which patient groups appear to be most undertreated; and which intervention strategies are effective.MethodsWe performed a comprehensive search of MEDLINE and systematically recorded the outcomes and quality of published studies, using five major criteria.ResultsTwenty-four studies were included in the analysis. The quality of the included studies was poor (31%) or moderate (37%). There was a longitudinal increase in quality of the studies and percentage of prevention. Multivariable linear regression showed that the quality of the study was the only independent predictor of the prevention rate reported in the study.ConclusionsThe results show undertreatment of CIOP might be due to insufficient quality of the studies rather than poor practice or failure to recognise the right patients. Future interventions should comply with five major quality criteria, and a multifaceted approach is required in order to make an impact on the underprescribing of CIOP prophylaxis.

A GASTROINTESTINAL SIMULATION SYSTEM (GISS) FOR DISSOLUTION OF DRUGS BEFORE AND AFTER ROUX-EN-Y GASTRIC BYPASS: FIRST RESULTS

S OF THE DUTCH SOCIETY OF CLINICAL PHARMACOLOGY AND BIOPHARMACY MEETING OF MARCH 26, 2013 DOPAMINE D2 AGONIST INDUCED CARDIOVASCULAR CHANGES IN YOUNG HEALTHY MEN. A PHASE I CLINICAL TRIAL EXPERIENCE K Abou Farha, S van Os, C Balje & W Tamminga QPS B.V, the Netherlands and Synthon BV, the Netherlands Introduction Dopamine D2 (DA2) agonists are a first line treatment option in young Parkinson’s patients with mild to moderate symptoms. DA2 agonists are known to cause depression of cardiac functions with decrease in heart rate. A recent European multicentre study [1] found a relationship between the use of DA2 agonists in Parkinson’s disease (PD) and heart failure (HF) especially in early phase of therapy. Results Here we present data of a Phase I study where we evaluated supine (SU) and standing (ST) blood pressure (BP) and brachial pulse rate (PR) levels, obtained from 40 healthy male volunteers, aged 18–55 year, after administration of a selective DA2 agonist. Full medical screening indicated the healthy status of all participants. The DA2 agonist was administered in an escalating dose level design over 30 days, 13 up-titration (UPT) days; 12 steady state (SS) days, and 5 down titration days. An oral dose of 10 mg domperidone tid was given to prevent potential D2 cardiovascular and gastrointestinal peripheral effects. Data were categorised into 2 age groups,G1 (18–40 years) and G2 (40–55 years). Statistical comparison between BP and brachial PR obtained in SU and ST positions during screening (BL), UPT phase and SS period revealed significant results (Table 1). All 40 subjects showed an increase in both SU and resting ST PR as compared to base line (with a zenith of 239 bpm in resting ST position vs. 60 bpm (BL). Increased SU Systolic (S)BP was observed in 36 subjects (26 G1 and 10 G2) with a zenith of 175 mmHg in 1 subject vs.138 mmHg). Increased ST SBP was observed in 33 subjects (24 G1 and 9 G2) with a zenith of 202 mmHg in 1 subject vs. 125 mmHg at BL. Seven of the 28 G1 subjects were removed prematurely from the trial because of clinically significant symptomatic increase in BP (up to 202/95 mmHg, ca. 81 mmHg and 20 mmHg increase respectively in SBP and DPB above BL) and tachycardia of 151 bpm, obtained from a 12leads ECG. In 3 of the 7 subjects non-specific ST-segment depression was seen in the inferior limb leads of concurrently obtained ECG (Figure 1). The clinical condition implied immediate administration of I.V. rescue medications including a selective β-1 blocker in all 7 subjects. In 1 subject with an inadequate response an I.V. α-β-1 blocking agent was added to therapy. Table 1 Systolic blood pressure (SBP) and brachial pulse rate (PR) for group 1 (18–40 years) and group 2 (40–55 years) in supine and standing position during screening (BL), UPT and SS phase Parameter Supine Standing

Doctors' beliefs and knowledge on corticosteroid-induced osteoporosis

What is known and Objective:  Despite the availability of effective treatments for the management of corticosteroid‐induced osteoporosis (CIOP), the condition is undertreated. Our objective was to assess prescribers’ knowledge and likely prescribing patterns concerning the diagnosis and treatment of CIOP. Another goal was to identify key barriers to the use of preventive therapy in patients using long‐term corticosteroids.