Predicting prolonged length of hospital stay in older emergency department users: use of a novel analysis method, the Artificial Neural Network.

OBJECTIVE: To examine performance criteria (i.e., sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], likelihood ratios [LR], area under receiver operating characteristic curve [AUROC]) of a 10-item brief geriatric assessment (BGA) for the prediction of prolonged length hospital stay (LHS) in older patients hospitalized in acute care wards after an emergency department (ED) visit, using artificial neural networks (ANNs); and to describe the contribution of each BGA item to the predictive accuracy using the AUROC value. METHODS: A total of 993 geriatric ED users admitted to acute care wards were included in this prospective cohort study. Age >85years, gender male, polypharmacy, non use of formal and/or informal home-help services, history of falls, temporal disorientation, place of living, reasons and nature for ED admission, and use of psychoactive drugs composed the 10 items of BGA and were recorded at the ED admission. The prolonged LHS was defined as the top third of LHS. The ANNs were conducted using two feeds forward (multilayer perceptron [MLP] and modified MLP). RESULTS: The best performance was reported with the modified MLP involving the 10 items (sensitivity=62.7%; specificity=96.6%; PPV=87.1; NPV=87.5; positive LR=18.2; AUC=90.5). In this model, presence of chronic conditions had the highest contributions (51.3%) in AUROC value. CONCLUSIONS: The 10-item BGA appears to accurately predict prolonged LHS, using the ANN MLP method, showing the best criteria performance ever reported until now. Presence of chronic conditions was the main contributor for the predictive accuracy.

A regression tree for identifying combinations of fall risk factors associated to recurrent falling: a cross-sectional elderly population-based study.

BACKGROUND: Regression tree (RT) analyses are particularly adapted to explore the risk of recurrent falling according to various combinations of fall risk factors compared to logistic regression models. The aims of this study were (1) to determine which combinations of fall risk factors were associated with the occurrence of recurrent falls in older community-dwellers, and (2) to compare the efficacy of RT and multiple logistic regression model for the identification of recurrent falls. METHODS: A total of 1,760 community-dwelling volunteers (mean age ± standard deviation, 71.0 ± 5.1 years; 49.4 % female) were recruited prospectively in this cross-sectional study. Age, gender, polypharmacy, use of psychoactive drugs, fear of falling (FOF), cognitive disorders and sad mood were recorded. In addition, the history of falls within the past year was recorded using a standardized questionnaire. RESULTS: Among 1,760 participants, 19.7 % (n = 346) were recurrent fallers. The RT identified 14 nodes groups and 8 end nodes with FOF as the first major split. Among participants with FOF, those who had sad mood and polypharmacy formed the end node with the greatest OR for recurrent falls (OR = 6.06 with p < 0.001). Among participants without FOF, those who were male and not sad had the lowest OR for recurrent falls (OR = 0.25 with p < 0.001). The RT correctly classified 1,356 from 1,414 non-recurrent fallers (specificity = 95.6 %), and 65 from 346 recurrent fallers (sensitivity = 18.8 %). The overall classification accuracy was 81.0 %. The multiple logistic regression correctly classified 1,372 from 1,414 non-recurrent fallers (specificity = 97.0 %), and 61 from 346 recurrent fallers (sensitivity = 17.6 %). The overall classification accuracy was 81.4 %. CONCLUSIONS: Our results show that RT may identify specific combinations of risk factors for recurrent falls, the combination most associated with recurrent falls involving FOF, sad mood and polypharmacy. The FOF emerged as the risk factor strongly associated with recurrent falls. In addition, RT and multiple logistic regression were not sensitive enough to identify the majority of recurrent fallers but appeared efficient in detecting individuals not at risk of recurrent falls.

Do not resuscitate orders and aging: impact of multimorbidity on the decision-making process.

BACKGROUND: The "Do Not Resuscitate" orders (DNR) are defined as advance medical directives to withhold cardiopulmonary resuscitation during cardiac arrest. Age-related multimorbidity may influence the DNR decision-making process. Our objective was to perform a systematic review and meta-analysis of published data examining the relationship between DNR orders and multimorbidity in older patients. METHODS: A systematic Medline and Cochrane literature search limited to human studies published in English and French was conducted on August 2012, with no date limits, using the following Medical Subject Heading terms: "resuscitation orders" OR "do-not-resuscitate" combined with "aged, 80 and over" combined with "comorbidities" OR "chronic diseases". RESULTS: Of the 65 selected studies, 22 met the selection criteria for inclusion in the qualitative analysis. DNR orders were positively associated with multimorbidity in 21 studies (95%). The meta-analysis included 7 studies with a total of 27,707 participants and 5065 DNR orders. It confirmed that multimorbidity were associated with DNR orders (summary OR = 1.25 [95% CI: 1.19-1.33]). The relationship between DNR orders and multimorbidity differed according to the nature of morbidities; the summary OR for DNR orders was 1.15 (95% CI: 1.07-1.23) for cognitive impairment, OR=2.58 (95% CI: 2.08-3.20) for cancer, OR=1.07 (95% CI: 0.92-1.24) for heart diseases (i.e., coronary heart disease or congestive heart failure), and OR=1.97 (95% CI: 1.61-2.40) for stroke. CONCLUSIONS: This systematic review and meta-analysis showed that DNR orders are positively associated with multimorbidity, and especially with three morbidities, which are cognitive impairment, cancer and stroke.

Derivation and validation of a Short Form of the Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint.

BACKGROUND AND PURPOSE: To validate a Short Form of the Mini-Mental State Examination (SMMSE) as a screening test for dementia in older ambulatory individuals followed in a memory clinic for a memory complaint. METHODS: A total of 202 cognitively healthy individuals, 100 individuals with a mild cognitive impairment and 304 demented individuals sent for a memory complaint by their primary care physician to a memory clinic were prospectively included in this cross-sectional study. They were randomized into derivation (n = 303) and validation (n = 303) groups. The SMMSE score was built from six memory items of MMSE, with a score ranging from 0 to 6 (i.e. best performance). RESULTS: The receiver operating characteristic curve showed an area under the curve of 0.98 for the derivation group and 0.97 for the validation group without differences between curves (P = 0.254). The cut-off between the sensitivity and the specificity of the SMMSE score for clinically diagnosed dementia was ≤4. The performance of the SMMSE for the diagnosis of dementia was high in the derivation and validation groups: sensitivity at 93.1% and 93.8%, specificity at 93.8% and 90.5%, positive predictive value at 94.3% and 90.1%, negative predictive value at 92.5% and 94.0%, likelihood ratio of positive test at 14.9 and 9.8 and of negative test at 0.07 and 0.07, respectively. CONCLUSIONS: The Short Form of the Mini-Mental State Examination was a good screening test for dementia in older individuals followed in a memory clinic for a memory complaint. The next step should be the confirmation of its discriminative value in older primary care patients.

[Abuse of alcohol and benzodiazepine during substitution therapy in heroin addicts: a review of the literature]. / Abus d'alcool et de benzodiazépines lors des traitements de substitution chez l'héroïnomane : une revue de la littérature.

INTRODUCTION: In spite of its seriousness, dependence on alcohol and benzodiazepines during substitution treatment are poorly documented. Its frequency is nonetheless significant. According to studies, between one and two thirds of patients are affected. This consumption is under verbalized by patients and underestimated by carers. In one study, where the average diazepam doses were from 40 to 45 mg per day, 30% of the patients were taking 70 to 300 mg per day, two thirds having experimented with a fixed dose of 100mg. Benzodiazepines, especially diazepam and flunitrazepam, were studied versus placebo. Thus, 10 to 20mg of diazepam gave rise to euphoria, a sensation of being drugged, sedation and lessening of cognitive performance. The aim of this consumption is to potentiate the euphoria induced by opioids, a "boost" effect during the hour after taking it, or the calming of the outward signs of withdrawal. The most sought after molecules are the most sedative, those with pronounced plasmatic peaks, and the most accessible. LITERATURE FINDINGS: In multidependant subjects, opioid dependence had been earlier in adolescence, with a number of therapeutic failures. They had been faced with repetitive rejection and separation during childhood, medicolegal and social problems. Somatization, depression, anxiety and psychotic disorders are frequent in this subgroup. Heavy drinkers under methadone treatment are highly vulnerable to cocaine. Their behaviour is at risk, with exchange of syringes; their survival rate is 10 years less than that of moderate consumers of alcohol. Most are single, with a previous prison, psychiatric or addictive cursus and they present significant psychological vulnerability. For some authors, benzodiazepines indicate a psychiatric comorbidity. Methadone significantly reduces the consumption of alcohol by nonalcoholic heroin addicts. Although alcohol is an enzymatic inductor of methadone catabolism, with bell-shaped methadone plasma curves over 24 hours, a substitution treatment is recommended. It has a minimum impact on care, in spite of efficiency and retention in therapeutical programs, allowing the subject's inclusion in the framework of a more regular and sustained medical follow-up. Treatment of benzodiazepine dependence by a progressive regression of doses has little efficacy in subjects which cannot control how much medication they are taking. Certain authors have suggested maintenance treatments of clonezepam. The most appropriate therapeutic propositions are: (1) maintenance of therapeutic links though a framework of deliverance from flexible substitution treatment; (2) prevention by cautious prescribing and control of dispensing medication; (3) parallel treatment of psychiatric comorbidities and related personality disorders; (4) individual psychiatric treatment, either institutional or in consistent networks.

[Clinical and socio-demographic profile of patients with schizophrenia according to the antipsychotic treatment prescribed]. / Analyse du profil socio-démographique et clinique de patients schizophrènes en fonction du traitement neuroleptique reçu.

INTRODUCTION: Data concerning the characteristics of patients with schizophrenia and their treatment in day hospitals are scarce. Guidelines for clinical practice are, however, regularly published. Recommendations from the 1994 Consensus Conference underline the necessity of antipsychotic monotherapy in the long term treatment of schizophrenia. In the US the Schizophrenia Patient Outcome Research Team (PORT) published in 1999 treatment recommendations concerning the use of antipsychotics in the acute phase and in maintenance. For maintenance, the recommended dose should be between 300 and 600 mg/day (CPZ equivalents) (recommendation n 4). AIM OF THE STUDY: The aim of this study is to establish the socio-demographic and clinical profile of patients according to the dose of antipsychotic medication prescribed. The study also examines the use of antipsychotic polypharmacy. DESIGN: of the study. For this study, 116 patients treated in 12 different day hospital units were recruited. Inclusion criteria were: a DSM IV diagnosis of schizophrenia, being treated in a day hospital and having received antipsychotic medication for at last 2 months. Instruments were the MINI for a standardized diagnosis of schizophrenia, the CGI and the PANSS. Prescribed doses were transformed in chlorpromazine (CPZ) equivalents, in order to establish comparisons between patients. RESULTS: The population sample was composed of 72 male (61.5%) and 44 female (38.5%) patients. The mean age was 36.4 years old. The mean education level was 11.3 years. A large majority (n=103, 88%) of patients was celibate, 65 patients (55.6%) lived on their own, the others lived with their family (45 patients, 38.5%) or with a spouse (7 patients, 6%). A large majority of patients (75.6%) received some form of state allowance. Only 1.7% were receiving a salary. The mean antipsychotic dose was 660 mg/day and 68% of patients were treated with an atypical antipsychotic (amisulpride, clozapine, olanzapine, risperidone). Thirty-two percent of patients were treated with doses between 600 and 1,000 mg/day and 24% with doses above 1,000 mg/day. When comparing patients according to the dose level they were receiving (<300 mg/day; 300 to 599 mg/day; and 600 to 999 mg/day;>1,000 mg/day), there was no significant difference between groups for socio-demographic variables. Patients treated with doses below 300 mg/day had a better psychosocial profile and were more often treated with loxapine, haloperidol and risperidone. Patients treated with doses above 1,000 mg/day were more often receiving clozapine. There was still a substantial number of patients treated with conventional antipsychotics in the above 1,000 mg/day range. Patients receiving an antipsychotic monotherapy were more often treated with clozapine or olanzapine and presented a higher rate of positive symptoms. DISCUSSION: These results are discussed in comparison with present guidelines concerning the treatment of patients with schizophrenia.

A truncated FGF receptor blocks neural induction by endogenous Xenopus inducers.

We have examined the role of fibroblast growth factor (FGF) signalling in neural induction. The approach takes advantage of the fact that both noggin and the dominant negative mutant activin receptor (delta1XAR1) directly induce neural tissues in the absence of dorsal mesoderm. A truncated FGF receptor (XFD) is co-expressed with noggin or delta1XAR1 in both whole embryos and isolated animal caps. We demonstrate that inhibition of FGF signalling prevents neural induction by both factors. Furthermore, neural induction by organizers (the dorsal lip of blastopore and Hensen's node) is also blocked by inhibiting FGF signalling in ectoderm. It has been proposed that the specification of anterior neuroectoderm, including the cement gland, occurs in a sequential manner as gastrulation proceeds. We show that the specification of the most anterior neuroectoderm by noggin may occur before gastrulation and does not require FGF signalling, since both the cement gland marker XCG-1 and the anterior neural marker Otx-2 are normally expressed in ectodermal explants co-injected with noggin and XFD RNAs, but the cement gland cells are poorly differentiated. In contrast, the expression of both genes induced by CSKA.noggin, which is expressed after the mid-blastula transition, is strongly inhibited by the presence of XFD. Therefore the noggin-mediated neural induction that takes place at gastrula stages is abolished in the absence of FGF signalling. Since inhibition of FGF signalling blocks the neuralizing effect of different neural inducers that function through independent mechanisms, we propose that FGF receptor-related-signalling is required for the response to inducing signals of ectodermal cells from gastrula.

Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents.

Nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyano naphtalene-2-carboxamide) is a novel compound, which inhibits potently and stereoselectively [125I]iodosulpride binding at recombinant human dopamine D3 receptors. the levoisomer displays an apparent Ki value of 0.3 nM at the dopamine D3 receptor, but is 10 times less potent at the human recombinant dopamine D2 receptor. In comparison, the dextroisomer displays 20-fold less apparent affinity at the dopamine D3 receptor and reduced (2-fold) selectivity. l-Nafadotride displays iow, micromolar affinity at dopamine D1 and D4 receptors and negligible apparent affinity at various other receptors. In dopamine D3 receptor-transfected NG-108 15 cells, in which dopamine agonists increase mitogenesis, l-nafadotride has no intrinsic activity, but competitively antagonizes the quinpirole-induced mitogenetic response, monitored by [3H]thymidine incorporation with a pA2 of 9.6. In dopamine D2 receptor-transfected Chinese Hamster Ovary cells, l-nafadotride also behaves as a competitive antagonist of quinpirole-induced mitogenesis with an 11-fold lower potency. These studies establish nafadotride as a pure, extremely potent, competitive and preferential dopamine D3 receptor antagonist in vitro. l-Nafadotride displaces in vivo N-[3H]propylnorapomorphine accumulation at lower dosage and for longer periods in limbic structures, containing both dopamine D2 and D3 receptors than in the stratum, containing dopamine D2 receptor only. At low dosage (0.1-1 mg/kg), nafadotride, unlike haloperidol, a dopamine D2 receptor-preferring antagonist, increases spontaneous locomotion of habituated rats and climbing behavior of mice, at doses that do not modify striatal homovanillic acid levels. At high dosage (1-100 mg/kg), nafadotride, like haloperidol, produces catalepsy and antagonizes apomorphine-induced climbing.(ABSTRACT TRUNCATED AT 250 WORDS)