Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.

Background: Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP). Methodology and Principal Findings: We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the "viral dating" (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals. Conclusions: A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research.

The Emergence of Forensic Nursing and Advanced Nursing Practice in Switzerland: An Innovative Case Study Consultation.

BACKGROUND AND METHODS:: The objectives of this article were to systematically describe and examine the novel roles and responsibilities assumed by nurses in a forensic consultation for victims of violence at a University Hospital in French-speaking Switzerland. Utilizing a case study methodology, information was collected from two main sources: (a) discussion groups with nurses and forensic pathologists and (b) a review of procedures and protocols. Following a critical content analysis, the roles and responsibilities of the forensic nurses were described and compared with the seven core competencies of advanced nursing practice as outlined by Hamric, Spross, and Hanson (2009). RESULTS:: Advanced nursing practice competencies noted in the analysis included "direct clinical practice," "coaching and guidance," and "collaboration." The role of the nurse in terms of "consultation," "leadership," "ethics," and "research" was less evident in the analysis. DISCUSSION AND CONCLUSION:: New forms of nursing are indeed practiced in the forensic clinical setting, and our findings suggest that nursing practice in this domain is following the footprints of an advanced nursing practice model. Further reflections are required to determine whether the role of the forensic nurse in Switzerland should be developed as a clinical nurse specialist or that of a nurse practitioner.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Towards a diffusion image processing validation and accuracy prediction framework

Validation is the main bottleneck preventing theadoption of many medical image processing algorithms inthe clinical practice. In the classical approach,a-posteriori analysis is performed based on someobjective metrics. In this work, a different approachbased on Petri Nets (PN) is proposed. The basic ideaconsists in predicting the accuracy that will result froma given processing based on the characterization of thesources of inaccuracy of the system. Here we propose aproof of concept in the scenario of a diffusion imaginganalysis pipeline. A PN is built after the detection ofthe possible sources of inaccuracy. By integrating thefirst qualitative insights based on the PN withquantitative measures, it is possible to optimize the PNitself, to predict the inaccuracy of the system in adifferent setting. Results show that the proposed modelprovides a good prediction performance and suggests theoptimal processing approach.

Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

Background: There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Design Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. Methods: In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Results: Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Conclusion: Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.

Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation of current practice in a general surgery department.

RATIONALE, AIMS AND OBJECTIVES: There is little evidence regarding the benefit of stress ulcer prophylaxis (SUP) outside a critical care setting. Overprescription of SUP is not devoid of risks. This prospective study aimed to evaluate the use of proton pump inhibitors (PPIs) for SUP in a general surgery department. METHOD: Data collection was performed prospectively during an 8-week period on patients hospitalized in a general surgery department (58 beds) by pharmacists. Patients with a PPI prescription for the treatment of ulcers, gastro-oesophageal reflux disease, oesophagitis or epigastric pain were excluded. Patients admitted twice during the study period were not reincluded. The American Society of Health-System Pharmacists guidelines on SUP were used to assess the appropriateness of de novo PPI prescriptions. RESULTS: Among 255 patients in the study, 138 (54%) received a prophylaxis with PPI, of which 86 (62%) were de novo PPI prescriptions. A total of 129 patients (94%) received esomeprazole (according to the hospital drug policy). The most frequent dosage was at 40 mg once daily. Use of PPI for SUP was evaluated in 67 patients. A total of 53 patients (79%) had no risk factors for SUP. Twelve and two patients had one or two risk factors, respectively. At discharge, PPI prophylaxis was continued in 33% of patients with a de novo PPI prescription. CONCLUSIONS: This study highlights the overuse of PPIs in non-intensive care unit patients and the inappropriate continuation of PPI prescriptions at discharge. Treatment recommendations for SUP are needed to restrict PPI use for justified indications.

Prédire la survenue d'un diabète: la place de scores cliniques et/ou génétiques [Genetic and/or clinical scores to anticipate the onset of diabetes]

Diabetes represents an important health burden on our society: for example in Lausanne (Switzerland) 16% of the adult population have abnormal glucose homeostasis and 6% have diabetes, of which about a third is not aware. Some guidelines identify the "at risk" population for which screening seems indicated. Simple clinical scores have been developed at allow to better estimate the risk of diabetes and hence to potentially better target screening of the disease. The recent discovery of more that 18 genetic variants associated with an increased risk to develop the diseased has allowed to include individual genotype into genetic risk scores. We will discuss in this article the usefulness of these genetic score, how they compare to clinical score, their implication for clinical practice as well as their potential ethical or economical consequences.

Official Positions for FRAX® Bone Mineral Density and FRAX® simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.

Catheterisation. Indwelling catheters in adults. Urethral and suprapubic. Evidence-based guidelines for best practice in urological health care

The EAUN Guidelines Working Group for indwelling catheters have prepared this guideline document to help nurses assess the evidence-based management of catheter care and to incorporate the guidelines’ recommendations into their clinical practice. These guidelines are not meant to be proscriptive, nor will adherence to these guidelines guarantee a successful outcome in all cases. Ultimately, decisions regarding care must be made on a case-by-case basis by healthcare professionals after consultation with their patients using their clinical judgement, knowledge and expertise.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Impact of geographical and cultural factors on clinical trials in acute mania: lessons from a ziprasidone and haloperidol placebo-controlled study

Clinical trials today are conducted in multiple countries to enhance patient recruitment and improve efficiency of trials. However, the demographic and cultural diversity may contribute to variations in study outcomes. Here we conducted post-hoc analyses for a placebo-controlled study with ziprasidone and haloperidol for the treatment of acute mania to address the demographic, dosing, and outcome disparities in India, Russia and the USA. We compared the baseline characteristics, outcomes and discontinuations in patients and explored the relationship between the outcome measures across these countries. We found substantial differences in baseline characteristics of subjects, administered dosage and disease severity in India compared to the USA and Russia. Conversely, US subjects had a higher placebo response compared to subjects in Russia and India. These results are probably due to demographic differences in patient populations and psychiatric clinical practice across countries. While we offer initial ideas to address the disparities identified in this analysis, it is clear that further research to improve our understanding of geographical differences is essential to ensure globally applicable results for clinical trials in psychiatry.

Brief cognitive assessment instruments in schizophrenia and bipolar patients, and healthy control subjects: A comparison study between the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP)

Cognitive impairment in schizophrenia and psychosis is ubiquitous and acknowledged as a core feature of clinical expression, pathophysiology, and prediction of functioning. However, assessment of cognitive functioning is excessively time-consuming in routine practice, and brief cognitive instruments specific to psychosis would be of value. Two screening tools have recently been created to address this issue, i.e., the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP). The aim of this research was to examine the comparative validity of these two brief instruments in relation to a global cognitive score. 161 patients with psychosis (96 patients diagnosed with schizophrenia and 65 patients diagnosed with bipolar disorder) and 76 healthy control subjects were tested with both instruments to examine their concurrent validity relative to a more comprehensive neuropsychological assessment battery. Scores from the B-CATS and the SCIP were highly correlated in the three diagnostic groups, and both scales showed good to excellent concurrent validity relative to a Global Cognitive Composite Score (GCCS) derived from the more comprehensive examination. The SCIP-S showed better predictive value of global cognitive impairment than the B-CATS. Partial and semi-partial correlations showed slightly higher percentages of both shared and unique variance between the SCIP-S and the GCCS than between the B-CATS and the GCCS. Brief instruments for assessing cognition in schizophrenia and bipolar disorders, such as the SCIP-S and B-CATS, seem to be reliable and promising tools for use in routine clinical practice.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Le point sur la pratique infirmière avancée [Update on advanced practice nursing].

NlmCategory="UNASSIGNED">We report outcomes of a clinical audit examining criteria used in clinical practice to rationalize endotracheal tube (ETT) suction, and the extent these matched criteria in the Endotracheal Suction Assessment Tool(ESAT)©. A retrospective audit of patient notes (N = 292) and analyses of criteria documented by pediatric intensive care nurses to rationalize ETT suction were undertaken. The median number of documented respiratory and ventilation status criteria per ETT suction event that matched the ESAT© criteria was 2 [Interquartile Range (IQR) 1-6]. All criteria listed within the ESAT© were documented within the reviewed notes. A direct link was established between criteria used for current clinical practice of ETT suction and the ESAT©. The ESAT©, therefore, reflects documented clinical decision making and could be used as both a clinical and educational guide for inexperienced pediatric critical care nurses. Modification to the ESAT© requires "preparation for extubation" to be added.

Pharmacogenetic and clinical study on adverse effects induced by psychotropic drugs

Second-generation antipsychotics (SGAs) have become the first-line antipsychotic treatment for psychotic disorders due to their better overall tolerance compared to classical antipsychotics. However, metabolic side effects such as weight gain are frequently described during treatment with SGAs and/or other psychotropic drugs including some antidepressants and mood stabilizers, which may also result in poor adherence to treatment. The aim of this work was to investigate different methods to predict common side effects, in particular weight gain during treatment with weight gain inducing psychotropic drugs. Firstly, clinical data were used to determine the potential predictive power of a one month weight gain on weight increase after three and 12 months of treatment (n=351 patients). A fast and strong weight gain of >5% after a period of one month (>5%WG) was found to be the best predictor for an important weight gain at three (>15%) and 12 months (>20%). Similar analyses in an independent cohort of psychiatric adolescents (n=42), showed that a comparable >4% weight gain at one month is the best predictor for an important weight gain at three months (>15%). Secondly, we aimed to determine whether an extensive analysis of genes could be used, in addition to clinical factors, to predict patients at risk for >5%WG or for type 2 diabetes (T2D). Adding genetic markers to clinical variables to predict >5%WG increased significantly the area under the curve (AUC) of the analysis (AUCfinai:0.92, AUCdmicai:0.75, pcO.OOOl, n=248). Conversely, genetic risk scores were found to be associated with T2D (OR: 2.5, p=0.03, n=285) but without a significant increase of AUC'when compared to the prediction based to clinical factors alone. Finally, therapeutic drug monitoring was used to predict extrapyramidal symptoms during risperidone treatment (n=150). Active moiety (sum of risperidone and of its active metabolite 9- hydroxyrisperidone plasma concentrations) of >40 ng/ml should be targeted only in case of insufficient response. These results highlight different approaches for personalizing psychotropic treatments in order to reduce related side effects. Further research is needed, in particular on the identification of genetic markers, to improve the implementation of these results into clinical practice. Résumé Les antipsychotiques atypiques (APA) sont devenus le traitement antipsychotique de première intention pour le traitement des psychoses, grâce à un profil d'effets secondaires plus favorables comparé aux antipsychotiques typiques. Néanmoins, d'autres effets indésirables d'ordre métabolique (ex. prise pondérale) sont observés sous APA, stabilisateurs de l'humeur et/ou certains antidépresseurs, pouvant aussi limiter l'adhérence au traitement. L'objectif de ce travail est d'explorer différentes méthodes permettant de prédire des effets secondaires courants, en particulier la prise de poids durant un traitement avec des psychotropes pouvant induire un tel effet. Dans une première partie, des données cliniques ont été évaluées pour leurs potentiels prédictifs d'une prise de poids à un mois sur une prise de poids à trois et 12 mois de traitement (n=351 patients). Une prise de poids rapide et forte >5% à un mois (PP>5%) s'est avérée être le meilleur prédicteur pour une prise pondérale importante à trois (>15%) et 12 (>20%) mois de traitement. Des analyses similaires dans une cohorte pédiatrique (n=42) ont indiqué une prise de poids >4% à un mois comme le meilleur prédicteur pour une prise pondérale importante (>15%) à trois mois de traitement. Dans une deuxième partie, des marqueurs génétiques, en complément aux données cliniques, ont été analysés pour leur contribution potentielle à la prédiction d'une PP>5% et au dépistage du diabète de type 2 (DT2). L'ajout de variants génétiques aux données cliniques afin de prédire une PP>5% a augmenté significativement l'aire sous la courbe (ASC) de l'analyse (ASCflnai:0.92, ASCC|inique:0.75, p<0.0001, n=248). Concernant le DT2, un score génétique est associé au DT2 (OR: 2.5, p=0.03, n=285), néanmoins aucune augmentation significative de l'ASC n'a été observée par rapport à l'analyse avec les données cliniques seules. Finalement, des mesures de concentrations plasmatiques de médicaments ont été utilisées pour prédire la survenue de symptômes extrapyramidaux sous rispéridone (n=150). Cette analyse nous a permis d'établir qu'une concentration plasmatique de rispéridone associée à son métabolite actif >40 ng/ml ne devrait être recherchée qu'en cas de réponse clinique insuffisante. Ces différents résultats soulignent différentes approches pour personnaliser la prescription de psychotropes afin de réduire la survenue d'effets secondaires. Des études supplémentaires sont néanmoins nécessaires, en particulier sur l'identification de marqueurs génétiques, afin d'améliorer l'implémentation de ces résultats en pratique clinique. Résumé large publique Les antipsychotiques atypiques et autres traitements psychotropes sont couramment utilisés pour traiter les symptômes liés à la schizophrénie et aux troubles de l'humeur. Comme pour tout médicament, des effets secondaires sont observés. L'objectif de ce travail est d'explorer différentes méthodes qui permettraient de prédire la survenue de certains effets indésirables, en particulier une prise de poids et la survenue d'un diabète. Dans une première partie, nous avons évalué l'effet d'une prise de poids précoce sur une prise de poids au long terme sous traitement psychotrope. Les analyses ont mis en évidence dans une population psychiatrique qu'une prise de poids à un mois >5% par rapport au poids initial permettait de prédire une prise pondérale importante après trois (>15%) et 12 (>20%) mois de traitement. Un résultat semblable a. été observé dans un autre groupe de patients exclusivement pédiatriques. Dans une deuxième partie, nous avons évalué la contribution potentielle de marqueurs génétiques à la prédiction d'une prise pondérale de >5% après un mois de traitement ainsi que dans la survenue d'un diabète de type 2. Pour la prise de poids, la combinaison des données génétiques aux données cliniques a permis d'augmenter de 17% la précision de la prédiction, en passant de 70% à 87%. Concernant la survenue d'un diabète, les données génétiques n'ont pas amélioré la prédiction. Finalement, nous avons analysé la relation possible entre les concentrations sanguines d'un antipsychotique atypique couramment utilisé, la rispéridone, et la survenue d'effets secondaires (ici les tremblements). Il est ressorti de cette étude qu'une concentration plasmatique du médicament supérieure à 40 ng/ml ne devrait être dépassée qu'en cas de réponse thérapeutique insuffisante, au risque de voir augmenter la survenue d'effets secondaires du type tremblements. Ces résultats démontrent la possibilité de prédire avec une bonne précision la survenue de certains effets secondaires. Cependant, en particulier dans le domaine de la génétique, d'autres études sont nécessaires afin de confirmer les résultats obtenus dans nos analyses. Une fois cette étape franchie, il serait possible d'utiliser ces outils dans la pratique clinique. A terme, cela pourrait permettre au prescripteur de sélectionner les traitements les mieux adaptés aux profils spécifiques de chaque patient.