Appropriate use of antifungals: impact of an antifungal stewardship program on the clinical outcome of candidaemia in a French University Hospital.

OBJECTIVES: The objective of this study was to compare clinical outcomes of patients with candidaemia before and after implementation of an antifungal stewardship program (AFSP). METHODS: This study included all consecutive cases of candidaemia identified from January 2012 to December 2015 in a French University Hospital. Data were collected retrospectively for a period of 2 years before implementation of the AFSP, and prospectively for 2 years after. All cases were reviewed by a multidisciplinary panel of experts including infectiologists, a microbiologist and pharmacists to have a complete follow-up of patients. RESULTS: 33 and 37 patients were finally included in the first and second period, respectively. The sites of entry of the candidaemia cases studied were as follows: intraabdominal in 29 cases (41.4%), central venous catheter 21 (30.0%), other or unknown: 20 (28.6%). Infectiologist consultations increased from 36.4 to 86.5% between the two periods with a significative impact on daily blood cultures which were more frequently performed in the second period (p = 0.04), and the use of echinocandins which was more frequent in the second period (97.1% of cases vs 78.8%, p = 0.03). The 3-month mortality rate declined from 36.4% in the first period to 27.0% in the second period (p = 0.4). CONCLUSIONS: Despite the insufficient number of candidaemia cases and the presence of other unmodifiable risk factors of mortality which did not allow us to show a significant effect on the 3-month mortality, AFSP had a significant effect on daily blood cultures and echinocandin use as first-line therapy.

Control strategy for carbapenemase-producing Enterobacteriaceae in nursing homes: perspectives inspired from three outbreaks.

Three outbreaks of carbapenemase-producing Enterobacteriaceae (CPE) in three nursing homes in western France were retrospectively assessed. In all, ten cases of colonization or infection with CPE were detected upon admission in neighbouring hospitals. Antibiotic consumption or high frailty was infrequent among them. Nursing homes should be included in a regional strategy to limit CPE spread.

Contaminants in blood cultures: importance, implications, interpretation and prevention.

BACKGROUND: Despite the development of new microbiologic technologies, blood cultures (BCs) remain the first-line tool for the diagnosis of bloodstream infections. Their diagnostic value may be affected when a microorganism of questionable evidence is isolated-for example, coagulase-negative staphylococci, Bacillus spp., viridans group streptococci, Corynebacterium spp., Propionibacterium spp. and Micrococcus spp. Finally, making a correct diagnosis of pathogenicity (vs. contamination) is challenging. AIMS: To review the current ways of dealing with the problem of BC contaminants (BCCs) and to provide practical suggestions to decrease BCC rates. SOURCES: PubMed electronic databases and existing reviews were searched up to December 2017 to retrieve relevant publications related to the topic. CONTENTS: This review describes the burden of BCC and analyses the main current issues and controversies in interpreting the occurrence of potential BC contaminants. It focuses on the best-described approaches to decide whether BCC is present and discusses the different strategies of prevention in adults. IMPLICATIONS: Each institution should have an efficient policy to prevent BCC, emphasizing the importance of following guidelines for prescribing and collecting BCs. Training healthcare workers should focus on detrimental influence on patient care and highlight the work and costs due to contaminants. The accurate differentiation of a contaminant from a true pathogen relies on a multidisciplinary approach and the clinical judgement of experienced practitioners.

An explained variance-based genetic risk score associated with gestational diabetes antecedent and with progression to pre-diabetes and type 2 diabetes: a cohort study.

OBJECTIVE: To determine whether an explained-variance genetic risk score (GRS), with 36 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes (T2D), is also associated with gestational diabetes mellitus (GDM), and with the progression to pre-diabetes and T2D among women with prior GDM. DESIGN: A cohort study. SETTING: Clinical investigation unit of Laval University, Quebec, Canada. POPULATION: A cohort of 214 women with prior GDM and 82 controls recruited between 2009 and 2012. METHODS: Associations between the GRS and GDM. MAIN OUTCOMES MEASURES: GDM and prevalence of pre-diabetes and T2D. RESULTS: Women with prior GDM had a higher GRS compared with controls (38.6 ± 3.9, 95% CI 38.1-39.1, versus 37.4 ± 3.2, 95% CI 36.7-38.1; P < 0.0001). In women with prior GDM, the explained-variance GRS was higher for pre-diabetic women compared with women who remained normoglucotolerant at testing (1.21 ± 0.18, 95% CI 1.18-1.23, versus 1.17 ± 0.15, 95% CI 1.13-1.20; P < 0.0001). Similarly, women with T2D had a higher explained-variance GRS compared with women with prior GDM who remained normoglucotolerant (1.20 ± 0.18, 95% CI 1.14-1.25, versus 1.17 ± 0.17, 95% CI 1.13-1.20; P < 0.0001). The predictive effects of the explained-variance GRS, age, and body mass index (BMI), or the additive effects of the three variables, were tested for pre-diabetes and T2D. We observed an area under the curve of 0.6269 (95% CI 0.5638-0.6901) for age and BMI, and adding the explained-variance GRS into the model increased the area to 0.6672 (95% CI 0.6064-0.7281) for the prediction of pre-diabetes. CONCLUSIONS: An explained-variance GRS is associated with both GDM and progression to pre-diabetes and T2D in women with prior GDM.

Nutrigenomics - perspectives from registered dietitians: a report from the Quebec-wide e-consultation on nutrigenomics among registered dietitians.

BACKGROUND: Not all healthcare professionals are familiar with nutrigenomics. However, they recognise that nutrigenomics has great potential for the development of preventive health approaches. The present study aimed to provide an overall picture of the current situation about nutrigenomics in the practice of registered dietitians (RDs) from the province of Quebec (Canada). METHODS: Three hundred and seventy-three RDs members of the Ordre professionnel des diététistes du Québec completed an online survey that included 34 questions, most of which were closed-ended questions. RESULTS: Overall, 76.9% of RDs knew about nutrigenomics. Among RDs with <5 years of experience, 49.2% knew about genetic testing related to nutrition compared to 11.7% for RDs with over 25 years of experience. Currently, 75.9% of RDs working in clinical nutrition in the public sector consider that they do not have the basic knowledge to integrate nutrigenomics in their practice compared to 62.9% for RDs in private practice. When asked about main limitations of genetic testing related to nutrition, RDs considered that genetic testing does not consider the other determinants of health, that genetic testing and their results have poor accuracy, and that there is a lack of scientific evidence. Concerns remained about ethical and legal aspects and its difficult application as a result of poor understanding and/or interpretation by professionals and/or customers. The high costs of these tests were also noted as a limitation. CONCLUSIONS: Registered dietitians know and are interested in nutrigenomics, especially those with less experience, although they do not feel adequately qualified to integrate findings from nutrigenomics into their practice.

Fatal histoplasmosis in a non-HIV patient in French Guiana.

Histoplasmosis is an endemic fungal infection that causes no symptoms or minor self-limited illnesses in most cases. Severe forms are commonly reported in patients with immunodeficiency disorders; histoplasmosis is considered to be an opportunistic infection in patients with AIDS. We report a case of disseminated histoplasmosis in a patient with no induced active suppression of the immune response. The infection was fulminant, and antifungal treatment was delayed because of a misdiagnosis of tuberculosis.

Impact of Hurricane Rita storm surge on sugarcane borer (Lepidoptera: Crambidae) management in Louisiana.

Twelve thousand to 16,000 ha of Louisiana sugarcane (Saccharum spp.) fields were flooded by saltwater from the Hurricane Rita storm surge in September 2005. A four treatment, 12-replication study comparing storm surge flooded and nonflooded plant and ratoon sugarcane fields was conducted during summer 2006 to assess sugarcane borer, Diatraea saccharalis (F.), pest severity, pest control actions, and soil-associated arthropod abundance and diversity. Even with a significant 2.4-fold increase in the average number of insecticide applications used for D. saccharalis management in flooded fields, growers still incurred higher injury. A significant 2.8-fold reduction in the predaceous red imported fire ant, Solenopsis invicta Buren, was associated with the storm surge, whereas no reduction in abundance of other soil-associated arthropods was recorded. Arthropod diversity measured by the Shannon diversity index significantly increased by a factor of 1.3 in sugarcane fields flooded by the storm surge. Increase in D. saccharalis pest severity associated with the storm surge caused an estimated loss in revenue between $1.9 and $2.6 million to the Louisiana sugarcane industry for the 2006 production season.

Sodium lauryl sulfate increases the efficacy of a topical formulation of foscarnet against herpes simplex virus type 1 cutaneous lesions in mice.

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.

Neural correlates of semantic associative encoding in episodic memory.

Associations between individual items are the basic building blocks of learning and memory. Functional neuroimaging has now made it possible to study neural correlates of such associations. The present PET study examined three associative encoding conditions differing in the number of words (0, 1, or 2) semantically related to a third word representing the name of a semantic category. A recall task consisting in the presentation of the category names as cues for retrieving the other two members of the triads followed each encoding condition. As expected, retrieval performance increased as the number of semantic exemplars at encoding increased (10%, 43%, 70% items recalled, respectively). A first analysis (partial least squares, PLS) of the PET data identified task-related patterns of activity for associative encoding and cued-recall tasks. A second analysis identified brain regions whose activity was modulated by the number of semantic exemplars at encoding. Some of the task-related brain regions also showed modulated activity by semantic relatedness and consisted in the left inferior prefrontal cortex, right medial temporal lobe, fusiform gyrus and inferior temporal gyrus bilaterally. Some of these regions showed greater activity when words in a triad were unrelated, whereas others did so when the three words were semantically related. These regions have been consistently reported in previous functional neuroimaging studies of associative encoding and may constitute key structures in association formation.

Continuous performance test differences among schizophrenic out-patients living in high and low expressed emotion environments.

BACKGROUND: High expressed emotion (EE) in families reliably predicts relapse in schizophrenia leading to the assumption that high EE stresses patients and is the cause of relapse. Attempts at validating the stressful properties of high EE using autonomic skin conductance measures have been inconclusive. Since memory loaded vigilance tasks are sensitive to stress, we used a memory loaded version of the Continuous Performance Test (CPT) to see if test performance would change in the presence and absence of high or low EE relatives. If high EE was stressful, performance should decline in their presence of high EE relatives. If low EE was protective against stress performance should improve in the presence of low EE relatives. METHODS: The CPT was administered to 41 schizophrenic and 51 normal control participants. CPT testing was conducted in the absence, then presence, then absence of high or low EE relatives. RESULTS: Control participants had significantly greater CPT scores than schizophrenic participants; there was no effect of the relative's presence or absence on CPT performance for either the high or low EE group. Schizophrenic participants from high EE homes demonstrated significantly better, rather than worse, CPT scores than those in low EE homes. CONCLUSIONS: These findings fail to support the notion of high EE as stressor, but show that high EE and low EE patient groups perform a vigilance task significantly differently. We propose that patients from low EE groups may be underaroused relative to their high EE counterparts and that this underarousal leads to less than optimal performance on the CPT.

Protective effect of a thermoreversible gel against the toxicity of nonoxynol-9.

BACKGROUND AND OBJECTIVES: One major problem associated with the use of nonoxynol-9 is that it can induce local inflammation and ulceration of the vaginal and cervical mucosa that might favor the entry of pathogens. With the aim of developing a gel formulation that could be effective in preventing sexually transmitted infections, the authors have evaluated the capacity of a polyoxypropylene/polyoxyethylene polymer to reduce or eliminate the toxicity of nonoxynol-9. STUDY DESIGN: The cytotoxicity of nonoxynol-9 alone or incorporated into the gel was investigated in human cervical and colon epithelial cells and after daily intravaginal application for 2 weeks in rabbits. RESULTS: In vitro experiments showed that nonoxynol-9 was highly toxic to human cervical and colon epithelial cells in a dose-dependent manner. However, the incorporation of the spermicide into the gel markedly reduced its toxicity under the same experimental conditions. In vivo studies showed that in animals treated with nonoxynol-9, the spermicide was very toxic to the vaginal and cervical mucosa as evidenced by the presence of bleeding, irritation, epithelial disruption, necrosis, the accumulation of leukocytes in the submucosa, and the loss of integrity of the epithelial cells. Of prime importance, the incorporation of nonoxynol-9 into the gel markedly reduced the toxicity of this potent spermicide/microbicide. CONCLUSION: The gel formulation could be used as an interesting approach to eliminate the toxicity of potent spermicides/microbicides such as nonoxynol-9.

[Mothers of psychotic patients and their difficulties with the health care system]. / Les difficultées perçues par des mères de personnes atteintes de troubles psychotiques face au système de soins professionnels.

This article describes the difficulties perceived by mothers of people suffering from psychotic problems when coping with the healthcare system. The 99 interviewees were recruited through mutual help groups and hospitals. In addition to feeling left to themselves to care for their child, their main grievances relate to the fact that their child does not have access to workforce integration resources, that therapeutic follow-up (non-drug related) is inadequate and that they do not receive updates on the state of health of their child. Mothers belonging to mutual help groups are significantly more upset about the difficulties they encounter when coping with the healthcare system, in comparison to mothers who do not belong to such groups. In light of comments by experts and the interviewees, the authors make suggestions designed to improve existing services, as well as collaboration between healthcare teams and the families concerned.

Effects of neuroleptic reduction in schizophrenic outpatients receiving high doses.

This paper presents an open study which evaluated the clinical effects of a partial and progressive reduction in neuroleptic medication in 32 outpatients suffering from schizophrenia who were receiving high doses (equivalent of > or = 18 mg of oral haloperidol per day; EHL). After an observation period of twelve weeks, each subject's dose of neuroleptics was reduced by 50% at the rate of 10% every four weeks. Patients were receiving a mean of 62 mg per day EHL at the beginning of the study and 30 mg per day EHL at the completion of the study. After the reduction, the following was observed: 1. a significant but modest change in psychopathology: a decrease in negative symptoms and in the total score on Brief Psychiatric Rating Scale; and 2. a significant increase in tardive dyskinesia symptoms. Six subjects relapsed but five of them recovered without increasing their reduced medication. Results of this study are discussed in the context of trying to find a minimal maintenance dose in the treatment of schizophrenia. The relative paucity of change despite a large reduction in medication argues for reevaluation of dosage in patients on high or very high doses of neuroleptics. The results suggest that many patients taking high doses could be maintained on significantly lower doses of neuroleptics. With gradual reduction of medication it would seem that many patients who are receiving a high dose of neuroleptic can achieve a lower dose than their current maintenance level.

Cognitive-behavioral therapy of panic disorder with secondary major depression: a preliminary investigation.

Controlled studies indicate that cognitive-behavioral therapy eliminates panic attacks in greater than 80% of patients who suffer from panic disorder. However, because most of the screening procedures used in those studies called for excluding patients who were depressed, a question arises as to the extent to which these results apply to patients who are clinically depressed in addition to having panic attacks. Accordingly, an attempt was made in the present study to determine whether or not panic patients who are clinically depressed could be treated as successfully as those who are not clinically depressed. Two multiple baseline A-A1-A-B across-subjects designs were used, one to test 8 panic Ss with major depression and the second to test 7 panic Ss without major depression. In Baseline (A), Ss monitored their panic attacks daily. During the A1 phase, a program of information on panic attacks presented as psychotherapy was instituted to assess the effects of nonspecific factors, followed by a second baseline phase (A). Cognitive-behavioral therapy (B) was then introduced. Results showed that cognitive-behavioral therapy was significantly superior to information-based therapy in the reduction of panic attacks. No significant differences were found between depressed and nondepressed patients.

Study of the clinical utility of radioreceptor assay in outpatients with schizophrenia receiving high doses of neuroleptics.

A radioreceptor assay (RRA) was used to determine the neuroleptic plasma levels of 32 outpatients with schizophrenia receiving a high dose of neuroleptics (the equivalent of 18 mg or more of oral haloperidol per day) and undergoing a 50% partial and progressive reduction (ten percent each month for five months) in their medication. Plasma levels of neuroleptics were measured three times: before (T1) and immediately after the 50% reduction (T2) and five months later (T3). A linear correlation was observed between neuroleptic plasma levels obtained by RRA and the neuroleptic doses prescribed at T1 and T3. Furthermore, neuroleptic plasma levels were significantly lower at T3 than at T1. Concurrent evaluations of psychopathology were done using the Brief Psychiatric Rating Scale, and the results indicated that no correlation exists between neuroleptic plasma levels and the total rating scale scores at T1 but a significant correlation was observed at T3.

[Training of interviewers in the utilization of standardized questionnaires in psychiatry: studies realized with the Present State Examination (PSE)]. / La formation d'interviewers à l'utilisation de questionnaires standardisés en psychiatrie: travaux réalisés avec l'Examen Psychiatrique Standardisé (EPS).

Interview questionnaires offer more validity than self-administered format in exploring psychopathological or psychosocial phenomena of interest in psychiatric research. If used, special care needs to be paid to interviewers' training and ensuring that they maintain their reliability. No widespread training standards exist and each schedule may carry its own procedure. Our aims are to indicate how we trained interviewers with the French version of the Present State Examination (Wing, Cooper and Sartorius, 1974) and how we checked and kept acceptable interraters reliability during one study. We will provide data on the interraters reliability during the training and the study, as well as the test-retest reliability. These results will be used to support some guidelines when using this sort of psychiatric research questionnaires in order to ensure comparability both within the study and between studies.

[Who are the patients treated in an outpatient clinic with high dosage neuroleptics?]. / Qui sont les patients traités en clinique externe avec des doses élevées de neuroleptiques?

The use of high doses of neuroleptics (NL) in treatment of chronic psychosis is a controversial subject in the literature. In this context, it is surprising to note the lack of objective data about the prevalence and the consequences concerning this mode of prescription when treating people suffering from severe mental disorders. This study describes the clientele exposed to high doses of NL from an outpatient clinic of a psychiatric hospital. The equivalent of 18 mg or more of haloperidol per day was used as the high dose criterion. Overall, we observed the use of NL in all diagnostic categories and the frequent use of polypharmacy in patients treated with NL. Among the 435 patients receiving NL, 26.4% had high dose prescriptions (two men for every woman). Most of these high dose NL subjects had a diagnosis of schizophrenic disorder (87.9%). Fifty-one of them had been receiving high doses for six months or more and 39 of them agreed to meet our research team. The mean age of these subjects was 37.2 years and the mean dose was 63.5 mg haloperidol equivalent/day. Thirty-five subjects were diagnosed as chronic schizophrenic disorder and four as schizo-affective disorder. Nineteen patients had tardive dyskinesia. In two out of three cases the high dose prescription began during hospitalization and the main reason was presence of severe psychotic symptoms. Significant positive correlations were found between parkinsonian symptoms and negative symptoms of schizophrenia as well as psychosocial dysfunctions on 39 subjects. These findings support the hypothesis that the use of high doses of NL contribute to the negative symptoms and the psychosocial dysfunctions. The implications of these findings relating to assessment and treatment of schizophrenic outpatients are discussed.

[Identifying mental health service needs of persons with schizophrenia]. / Combler les besoins de services de santé mentale des personnes atteintes de schizophrénie.

The present study aimed to identify the needs and describe the use of twenty mental health services in a population of chronic schizophrenic patients living in two regions in Quebec (Estrie and Centre-Sud). An attempt was also made to determine the principal reasons for which some services were not being used when they were identified as clinically required. The population considered was composed of the patients (N = 88) who had been discharged from the psychiatric care units of five general hospitals over a period of five months in 1982, and for whom the attending psychiatrist could confirm with certainty a diagnosis of chronic schizophrenia in accordance with the criteria of DSM-III. Medical files of these patients were reviewed, and the patients and psychiatrists themselves were interviewed separately regarding the patients' needs and use of twenty mental health services over the period from the seventh to the twelfth month after discharge from hospital. Results of the study show that services which were most often identified as clinically required were: 1) taking of neuroleptics, 2) organization of leisure activities, 3) case management, and 4) individual supportive therapy. At the same time, results indicate a poor fit between needs and use for most of rehabilitation and psychosocial services. The main reasons for non-use of services which were identified as clinically required are also presented. The implications of these results for the organization of mental health services for persons suffering from chronic schizophrenia are discussed, especially the importance of case management services.

[Needs and utilization of mental health services in schizophrenia]. / Besoins et utilisation de services de santé mentale dans la schizophrénie.

The planning of mental health treatment for people with severe mental disorders constitutes a major public health problem and an important social challenge. This study aims to identify the needs and to describe the utilisation of 20 services or modalities of mental health treatment among a schizophrenic population living in the Estrie region of Quebec. The results confirm that the needs are great and show that the most important deficiencies are in the psychosocial and readaptation services. The implications of these results with regard to the organisation of mental health services for schizophrenics are briefly discussed.