Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

We report the case of an 11-year-old female treated for mediastinal T-cell lymphoma who presented renal failure following the second cycle of high-dose methotrexate (HDMTX). Because of life threatening plasma methotrexate (MTX) levels, carboxypeptidase G2 (CPDG2) was administered resulting in a dramatic decrease within 1 hr. The patient recovered from renal failure and no other side effects were observed. Homozygosity for the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism diagnosed by molecular genetic analysis was the only explanation for this toxicity.

Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value.OBJECTIVE This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers.METHODS The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2.RESULTS Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes.CONCLUSION M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family.

Outpatient prescriptions practice and writing quality in a paediatric university hospital.

BACKGROUND: The writing of prescriptions is an important aspect of medical practice. This activity presents some specific problems given a danger of misinterpretation and dispensing errors in community pharmacies. The objective of this study was to determine the evolution of the prescription practice and writing quality in the outpatient clinics of our paediatric university hospital.¦METHODS: Copies of prescriptions written by physicians were collected from community pharmacies in the region of our hospital for a two-month period in 2005 and 2010. They were analysed according to standard criteria, including both formal and pharmaceutical aspects.¦RESULTS: A total of 597 handwritten prescriptions were reviewed in 2005 and 633 in 2010. They contained 1,456 drug prescriptions in 2005 and 1,348 in 2010. Fifteen drugs accounted for 80% of all prescriptions and the most common drugs were paracetamol and ibuprofen. A higher proportion of drugs were prescribed as International Nonproprietary Names (INN) or generics in 2010 (24.7%) compared with 2005 (20.9%). Of the drug prescriptions examined, 55.5% were incomplete in 2005 and 69.2% in 2010. Moreover in 2005, 3.2% were legible only with difficulty, 22.9% were ambiguous, and 3.0% contained an error. These proportions rose respectively to 5.2%, 27.8%, and 6.8% in 2010.¦CONCLUSION: This study showed that fifteen different drugs represented the majority of prescriptions, and a quarter of them were prescribed as INN or generics in 2010; and that handwritten prescriptions contained numerous omissions and preventable errors. In our hospital computerised prescribing coupled with advanced decision support is eagerly awaited.

Spurious hyperphosphatemia in a patient with alteplase-locked central venous catheter.

Alteplase has been shown to be effective in preventing central venous access clotting in patients on hemodialysis. Because of a high phosphorus content in its excipient, it can inadvertently contaminate blood samples, leading the physician in care of the patient to erroneously increase dialysis time or change diet in order to control the pseudo-hyperphosphatemia.

A highly sensitive LC-tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers.

The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented. Copyright © 2011 John Wiley & Sons, Ltd.

The career indecision profile : measurement equivalence in two international samples

This study tested for the measurement equivalence of a four-factor measure of career indecision (Career Indecision Profile-65 [CIP-65]) between a U.S. sample and two international samples; one composed of French-speaking young adults from France and Switzerland and the other of Italian ado- lescents. Previous research had supported the four-factor structure of the CIP-65 in both the United States and Iceland but also showed that items on two of the four scales may be interpreted differently by young adults growing up in these two countries. This study extends previous research by testing whether the four CIP-65 factors are measured equivalently in two additional international samples. Results largely supported the configural and metric invariance of the CIP-65 in the United States and international samples, but several scales showed a lack of scalar invariance. Some explanations are offered for these findings along with suggestions for future research and implications for practice.

Unlicensed and off-label drug use in a Swiss paediatric university hospital.

BACKGROUND: Many medicines used in newborns, infants, children and adolescents are not licensed ("unlicensed") or are prescribed outside the terms of the marketing authorization ("off-label"). Several studies have shown that this is a common practice in various healthcare settings in the USA, Europe and Australia, but data are scarce in Switzerland. OBJECTIVES: The aim of our prospective study was to determine the proportion of unlicensed or off-label prescriptions in paediatric patients. METHODS: This pilot study was conducted prospectively over a six month period in the department of paediatrics of a university hospital. RESULTS: Sixty patients aged from three days to 14 years were included in the study. A total of 483 prescriptions were written for the patients. More than half of all prescriptions (247; 51%) followed the terms of the marketing authorization. 114 (24%) were unlicensed and 122 (25%) off-label. All patients received at least one unlicensed or offlabel medicine. CONCLUSION: The use of unlicensed or off-label medicines to treat children was found to be common. Co-operation between the pharmaceutical industry, national regulatory authorities, clinical researchers, healthcare professionals and parents is required in order to ensure that children do not remain "therapeutic orphans".

Psychometric properties of the Marlowe-Crowne Social Desirability Scale in eight African countries and Switzerland

The purpose of this study was to assess the cross-cultural validity of the Marlowe-Crowne Social Desirability scale short form C, in a large sample of French-speaking participants from eight African countries and Switzerland. Exploratory and confirmatory analyses suggested retaining a two-factor structure. Item bias detection according to country was conducted for all 13 items and effect was calculated with R2. For the two-factor solution, 9 items were associated with a negligible effect size, 3 items with a moderate one, and 1 item with a large one. A series of analyses of covariance considering the acquiescence variable as a covariate showed that the acquiescence tendency does not contribute to the bias at item level. This research indicates that the psychometric properties of this instrument do not reach a scalar equivalence but that a culturally reliable measurement of social desirability could be developed.

Pediatric drug-related problems: a multicenter study in four French-speaking countries.

BACKGROUND: Pediatric intensive care patients represent a population at high risk for drug-related problems. There are few studies that compare the activity of clinical pharmacists between countries. OBJECTIVE: To describe the drug-related problems identified and interventions by four pharmacists in a pediatric cardiac and intensive care unit. SETTING: Four pediatric centers in France, Quebec, Switzerland and Belgium. METHOD: This was a six-month multicenter, descriptive and prospective study conducted from August 1, 2009 to January 31, 2010. Drug-related problems and clinical interventions were compiled from four pediatric centers in France, Quebec, Switzerland and Belgium. Data on patients, drugs, intervention, documentation, approval and estimated impact were compiled. MAIN OUTCOME MEASURE: Number and type of drug-related problems encountered in a large pediatric inpatient population. RESULTS: A total of 996 interventions were recorded: 238 (24 %) in France, 278 (28 %) in Quebec, 351 (35 %) in Switzerland and 129 (13 %) in Belgium. These interventions targeted 270 patients (median 21 months old, 53 % male): 88 (33 %) in France, 56 (21 %) in Quebec, 57 (21 %) in Switzerland and 69 (26 %) in Belgium. The main drug-related problems were inappropriate administration technique (29 %), untreated indication (25 %) and supra-therapeutic dose (11 %). The pharmacists' interventions were mostly optimizing the mode of administration (22 %), dose adjustment (20 %) and therapeutic monitoring (16 %). The two major drug classes that led to interventions were anti-infectives for systemic use (23 %) and digestive system and metabolism drugs (22 %). Interventions mainly involved residents and all clinical staff (21 %). Among the 878 (88 %) proposed interventions requiring physician approval, 860 (98 %) were accepted. CONCLUSION: This descriptive study illustrates drug-related problems and the ability of clinical pharmacists to identify and resolve them in pediatric intensive care units in four French-speaking countries.

Gender stereotypes of personality : universal and accurate ?

Numerous studies have documented subtle but consistent sex differences in self-reports and observer-ratings of five-factor personality traits, and such effects were found to show well- defined developmental trajectories and remarkable similarity across nations. In contrast, very little is known about perceived gender differences in five-factor traits in spite of their potential implications for gender biases at the interpersonal and societal level. In particular, it is not clear how perceived gender differences in five-factor personality vary across age groups and national contexts and to what extent they accurately reflect assessed sex differences in personality. To address these questions, we analyzed responses from 3,323 individuals across 26 nations (mean age = 22.3 years, 31% male) who were asked to rate the five-factor personality traits of typical men or women in three age groups (adolescent, adult, and older adult) in their respective nations. Raters perceived women as slightly higher in openness, agreeableness, and conscientiousness as well as some aspects of extraversion and neuroticism. Perceived gender differences were fairly consistent across nations and target age groups and mapped closely onto assessed sex differences in self- and observer-rated personality. Associations between the average size of perceived gender differences and national variations in sociodemographic characteristics, value systems, or gender equality did not reach statistical significance. Findings contribute to our understanding of the underlying mechanisms of gender stereotypes of personality and suggest that perceptions of actual sex differences may play a more important role than culturally based gender roles and socialization processes.

A 3-step therapeutic strategy for severe alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the terminal airways. Whole lung lavage (WLL) remains the gold standard treatment but may be particularly challenging in cases of severe hypoxemia. We present a 3-step strategy that was used in a patient with PAP-associated refractory hypoxemia and that combined venovenous extracorporeal membrane oxygenation (vvECMO), double-lumen orotracheal intubation, and bilateral multisegmental sequential lavage (MSL). The procedure was well tolerated and permitted weaning from the ventilator.

Demonstration of the effectiveness of zinc in diarrhoea of children living in Switzerland.

We designed a double-blinded randomized clinical trial of zinc (10 or 20 mg of zinc sulphate for 2-5 month-old or 6-59 month-old children, respectively, during 10 days) vs. placebo in otherwise healthy children aged 2 months to 5 years who presented with acute diarrhoea (i.e. ≥3 stools/day for less than 72 h). Eighty-seven patients (median age 14 months; range 3.1-58.3) were analysed in an intention-to-treat approach. Forty-two patients took zinc and 45 placebo. There was no difference in the duration nor in the frequency of diarrhoea, but only 5% of the zinc group still had diarrhoea at 120 h of treatment compared to 20% in the placebo group (P = 0.05). Thirty-one patients (13 zinc and 18 placebo) were available for per-protocol analyses. The median (IQR) duration of diarrhoea in zinc-treated patients was 47.5 h (18.3-72) and differed significantly from the placebo group (median 76.3; IQR 52.8-137) (P = 0.03). The frequency of diarrhoea was also lower in the zinc group (P = 0.02). CONCLUSION: zinc treatment decreases the frequency and severity of diarrhoea in children aged 2 months to 5 years living in Switzerland. However, the intention-to-treat analysis reveals compliance issues that question the proper duration of treatment and the choice of optimal pharmaceutical formulation.