Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.

BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018). CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.

Ageing with HIV: medication use and risk for potential drug-drug interactions.

OBJECTIVES: To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥ 50 years or <50 years. METHODS: All ART-treated participants were prospectively included once during a follow-up visit of the Swiss HIV Cohort Study. Information on any current medication was obtained by participant self-report and medical prescription history. The complete treatment was subsequently screened for PDDIs using a customized version of the Liverpool drug interaction database. RESULTS: Drug prescriptions were analysed for 1497 HIV-infected individuals: 477 age ≥ 50 and 1020 age <50. Older patients were more likely to receive one or more co-medications compared with younger patients (82% versus 61%; P < 0.001) and thus had more frequent PDDIs (51% versus 35%; P < 0.001). Furthermore, older patients tended to use a higher number of co-medications and certain therapeutic drug classes more often, such as cardiovascular drugs (53% versus 19%; P < 0.001), gastrointestinal medications (10% versus 6%; P = 0.004) and hormonal agents (6% versus 3%; P = 0.04). PDDIs with ART occurred mainly with cardiovascular drugs (27%), CNS agents (22%) and methadone (6%) in older patients and with CNS agents (27%), methadone (15%) and cardiovascular drugs (11%) in younger patients. The response to ART did not differ between the two groups. CONCLUSIONS: The risk for PDDIs with ART increased in older patients who take more drugs than their younger HIV-infected counterparts. However, medication use in older and younger patients did not differ in terms of effect on antiretroviral tolerability and response.

Polyarthrite rhumatoïde du sujet agé: présentation clinique et prise en charge [Late-onset rheumatoid arthritis: clinical presentation and management]

Onset of rheumatoid arthritis in an elderly patient is common, in fact more common than in younger subject. If the reality of true differences in clinical presentation between younger and older subjects remained discussed, the central point remains that the prognosis is not better in older patients. Finally, conventional disease-modifying antirheumatic drugs (DMARD) and biological treatments are as efficient and safe than in younger patients, and the same strict management objectives used for younger subjects must be applied in the elderly.

Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations.

BACKGROUND:: The frequently prescribed antidementia drug galantamine is extensively metabolized by the enzymes cytochrome P450 (CYP) 2D6 and CYP3A and is a substrate of the P-glycoprotein. We aimed to study the relationship between genetic variants influencing the activity of these enzymes and transporters with galantamine steady state plasma concentrations. METHODS:: In this naturalistic cross-sectional study, 27 older patients treated with galantamine were included. The patients were genotyped for common polymorphisms in CYP2D6, CYP3A4/5, POR, and ABCB1, and galantamine steady state plasma concentrations were determined. RESULTS:: The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamine plasma concentrations than heterozygous and homozygous CYP2D6 extensive metabolizers (median 2.9 versus 2.0 ng/mL·mg, P = 0.025, and 1.8 ng/mL·mg, P = 0.004), respectively. CONCLUSIONS:: The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.

Evolution of anaesthesia care and related events between 1996 and 2010 in Switzerland.

BACKGROUND: Anaesthesia Databank Switzerland (ADS) is a voluntary data registry introduced in 1996. Its ultimate goal is to promote quality in anaesthesiology. METHODS: The ADS registry analyses routinely recorded adverse events and provides benchmark comparisons between anaesthesia departments. Data collection comprises a set of 31 variables organised into three modules, one mandatory and two optional. RESULTS: In 2010, the database included 2,158,735 anaesthetic procedures. Over time, the proportions of older patients have increased, the largest group being aged 50-64 years. The percentage of patients with American Society of Anesthesiologists (ASA) status 1 has decreased while the percentage of ASA status 2 or 3 patients has increased. The most frequent comorbidities recorded were hypertension (21%), smoking (16%), allergy (15%) and obesity (12%). Between 1996 and 2010, 125,579 adverse events were recorded, of which 34% were cardiovascular, 7% respiratory, 39% technical and 20% non-specific. The most severe events were resuscitation (50%), oliguria (22%), myocardial ischaemia (17%) and haemorrhage (10%). CONCLUSION: Routine ADS data collection contributes to the monitoring of trends in anaesthesia care in Switzerland. The ADS system has proved to be usable in daily practice, although this remains a constant challenge that is highly dependent on local quality management and quality culture. Nevertheless, success in developing routine regular feedback to users to initiate discussions about anaesthetic events would most likely help strengthen departmental culture regarding safety and quality of care.

Autofluorescence Study In NR2E3 p.G56R-linked Autosomal Dominant Retinitis Pigmentosa In A Single Kindred

Purpose: To date, the genotype/phenotype correlation of p.G56R-linked autosomal dominant retinitis pigmentosa (ADRP) is limited to less than 10 kindred. The purpose of this study is to report an unusual appearance of fundus autofluorescence (AF) with NR2E3 p.G56R-linked ADRP in a single kindred.Methods: Patients were enrolled among three generations in a previously unreported family. Molecular diagnosis was performed on all exons of NR2E3 and a p.G56R mutation was identified in affected family members only. Examinations included fundus photography, visual fields, optical coherence tomography, AF, near-infrared AF and ISCEV-standard electrophysiology (ERG).Results: Among 10 examined family members, 5 were affected. The youngest and oldest patients were 16 and 65 years old, respectively. Fundus examination revealed a range of retinal disorder from normal to optic nerve pallor, attenuated arterial caliber and bone spicule-like pigment deposits. In all patients, AF showed a double hyperfluorescent ring; an inner paramacular ring which extension was comparable among patients and an outer ring along the vascular arcades which extended towards periphery in older patients and became hypofluorescent. Maximal scotopic ERGs when recordable showed an increased a/b wave ratio.Conclusions: A double hyperfluorescent ring on AF is an uncommon observation and might be a specific clinical finding in NR2E3 p.G56R-linked ADRP. The consistency of that finding in all affected members of our 3-generation family confirms a previous study. Further analysis is required to determine whether AF changes are associated with particular retinal layer abnormalities.

Gériatrie [Review in geriatric medicine]

Several studies published in 2008 underline the potential danger of polymedication in older patients and propose indicators to identify those at higher risk for adverse events. A study from Oregon highlighted the difficulties to diagnose depression in patients, especially older ones, who made a request for assisted suicide. The HYVET study demonstrated that treatment of hypertension is beneficial even in some very old persons. A meta-analysis confirmed the benefits from community-based geriatric interventional programs, in particular when targeting older individuals recently discharged from the hospital. Finally, mixed results were observed in the field of dementia.

Gériatrie aiguë: un modèle d'unité intégree de soins aux seniors [How to prevent functional decline: an acute care unit model for the elderly].

Hospitalization in older patients is frequently associated with functional decline. Hospital factors and inadapted process of care are factors leading to this decline. Acute care units specifically developed for older patients can prevent functional decline. These units usually include a comprehensive geriatric evaluation, an interdisciplinary meeting, protocols for the treatment of geriatric syndromes and specific teaching for the care team. Globally, patients' cares are organized to preserve and improve functional performances. This article presents a pilot unit inspired by this model.

Ensimmäiset päivät sairaalassa : viiden iäkkään potilaan havainnointi vuodeosastolla

English summary: First 72 hours in hospital : observation of five older patients on a ward

Loss to follow-up in an international, multicentre observational study.

OBJECTIVE: The aim of this work was to assess loss to follow-up (LTFU) in EuroSIDA, an international multicentre observational cohort study. METHODS: LTFU was defined as no follow-up visit, CD4 cell count measurement or viral load measurement after 1 January 2006. Poisson regression was used to describe factors related to LTFU. RESULTS: The incidence of LTFU in 12 304 patients was 3.72 per 100 person-years of follow-up [95% confidence interval (CI) 3.58-3.86; 2712 LTFU] and varied among countries from 0.67 to 13.35. After adjustment, older patients, those with higher CD4 cell counts, and those who had started combination antiretroviral therapy all had lower incidences of LTFU, while injecting drug users had a higher incidence of LTFU. Compared with patients from Southern Europe and Argentina, patients from Eastern Europe had over a twofold increased incidence of LTFU after adjustment (incidence rate ratio 2.16; 95% CI 1.84-2.53; P<0.0001). A total of 2743 patients had a period of >1 year with no CD4 cell count or viral load measured during the year; 743 (27.1%) subsequently returned to follow-up. CONCLUSIONS: Some patients thought to be LTFU may have died, and efforts should be made to ascertain vital status wherever possible. A significant proportion of patients who have a year with no follow-up visit, CD4 cell count measurement or viral load measurement subsequently return to follow-up.

Diabète et démence: tes liaisons dangereuses [Diabetes and dementia: the dangerous liaisons? ].

As population ages, a growing number of older patients present the constellation of diabetes and dementia. Numerous recent studies highlight that diabetes may increase the risk for Alzheimer and vascular dementia. Among patients with previous severe hypoglycemia, that risk may even double. Inversely demented patients have about three times higher risk of hypoglycemia. Given that spiral link between hypoglycemia and dementia, the latter should be considered as a possible complication of diabetes and consistently be screened for among older diabetic patients. Furthermore, the American Diabetes Association and American Geriatric Society consensus recommends a more flexible glycemic treatment goal of AIC among demented patients, with a target range between 8 and 9%.

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

AIMS: A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. METHODS: A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. RESULTS: The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. CONCLUSION: The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.

Gériatrie [What's new in geriatric medicine]

Several studies clarified the role of different interventions such as vitamine D replacement, denosumab treatment, and vertebroplasty in the prevention and management of falls and fractures. A trial tested the effectiveness of pharmaceutical assistance at the time of discharge, emphasizing the potential benefits for the patients and the health care system. Syncopal episodes frequently lead to hospital admission. A retrospective study evaluated the diagnostic yield of different tests and emphasized the importance to actively seek orthostatic hypotension in older patients. Finally, advances remain modest in the field of dementias.

A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up.

This study compared the outcome of total knee replacement (TKR) in adult patients with fixed- and mobile-bearing prostheses during the first post-operative year and at five years' follow-up, using gait parameters as a new objective measure. This double-blind randomised controlled clinical trial included 55 patients with mobile-bearing (n = 26) and fixed-bearing (n = 29) prostheses of the same design, evaluated pre-operatively and post-operatively at six weeks, three months, six months, one year and five years. Each participant undertook two walking trials of 30 m and completed the EuroQol questionnaire, Western Ontario and McMaster Universities osteoarthritis index, Knee Society score, and visual analogue scales for pain and stiffness. Gait analysis was performed using five miniature angular rate sensors mounted on the trunk (sacrum), each thigh and calf. The study population was divided into two groups according to age (≤ 70 years versus > 70 years). Improvements in most gait parameters at five years' follow-up were greater for fixed-bearing TKRs in older patients (> 70 years), and greater for mobile-bearing TKRs in younger patients (≤ 70 years). These findings should be confirmed by an extended age controlled study, as the ideal choice of prosthesis might depend on the age of the patient at the time of surgery.

Médecine d'urgence [Emergency medicine: updates 2012].

We review some of the most influential papers from 2012 in the different aspects of emergency medicine, such as prehospital medicine, resuscitation, early diagnosis and timely ED discharge and treatment. In particular, intramuscular benzodiazepines have been shown to be efficient in prehospital status epilepticus, epinephrines usefulness in cardiopulmonary resuscitation has been challenged, colloids have been shown to be deleterious in the treatment of severe sepsis and septic shock, the time window for thrombolysis in acute stroke will probably be extended, acute pyelonephritis treatment duration can be decreased, new D-dimers thresholds for older patients may prevent further diagnosis tests, and hs-Troponin may allow earlier discharge of low coronary risk patients.