Cyberhealth serving to support individual intake of medication.

The Internet and new communication technologies are deeply affecting healthcare systems and the provision of care. The purpose of this article is to evaluate the possibility that cyberhealth, via the development of widespread easy access to wireless personal computers, tablets and smartphones, can effectively influence intake of medication and long-term medication adherence, which is a complex, difficult and dynamic behaviour to adopt and to sustain over time. Because of its novelty, the impact of cyberhealth on drug intake has not yet been well explored. Initial results have provided some evidence, but more research is needed to determine the impact of cyberhealth resources on long-term adherence and health outcomes, its user-friendliness and its adequacy in meeting e-patient needs. The purpose of such Internet-based interventions, which provide different levels of customisation, is not to take over the roles of healthcare providers; on the contrary, cyberhealth platforms should reinforce the alliance between healthcare providers and patients by filling time-gaps between visits and allowing patients to upload and/or share feedback material to be used during the visits. This shift, however, is not easily endorsed by healthcare providers, who must master new eHealth skills, but healthcare systems have a unique opportunity to invest in the Internet and to use this powerful tool to design the future of integrated care. Before this can occur, however, important issues must be addressed and resolved, for example ethical considerations, the scientific quality of programmes, reimbursement of activity, data security and the ownership of uploaded data.

Atrioventricular septal defects among infants in Europe: a population-based study of prevalence, associated anomalies, and survival.

OBJECTIVE: To describe the epidemiology of chromosomal and non-chromosomal cases of atrioventricular septal defects in Europe. METHODS: Data were obtained from EUROCAT, a European network of population-based registries collecting data on congenital anomalies. Data from 13 registries for the period 2000-2008 were included. RESULTS: There was a total of 993 cases of atrioventricular septal defects, with a total prevalence of 5.3 per 10,000 births (95% confidence interval 4.1 to 6.5). Of the total cases, 250 were isolated cardiac lesions, 583 were chromosomal cases, 79 had multiple anomalies, 58 had heterotaxia sequence, and 23 had a monogenic syndrome. The total prevalence of chromosomal cases was 3.1 per 10,000 (95% confidence interval 1.9 to 4.3), with a large variation between registers. Of the 993 cases, 639 cases were live births, 45 were stillbirths, and 309 were terminations of pregnancy owing to foetal anomaly. Among the groups, additional associated cardiac anomalies were most frequent in heterotaxia cases (38%) and least frequent in chromosomal cases (8%). Coarctation of the aorta was the most common associated cardiac defect. The 1-week survival rate for live births was 94%. CONCLUSION: Of all cases, three-quarters were associated with other anomalies, both chromosomal and non-chromosomal. For infants with atrioventricular septal defects and no chromosomal anomalies, cardiac defects were often more complex compared with infants with atrioventricular septal defects and a chromosomal anomaly. Clinical outcomes for atrioventricular septal defects varied between regions. The proportion of termination of pregnancy for foetal anomaly was higher for cases with multiple anomalies, chromosomal anomalies, and heterotaxia sequence.

Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters.

BACKGROUND: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS: In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopist's clinical judgement.

Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score.

The predictive potential of six selected factors was assessed in 72 patients with primary myelodysplastic syndrome using univariate and multivariate logistic regression analysis of survival at 18 months. Factors were age (above median of 69 years), dysplastic features in the three myeloid bone marrow cell lineages, presence of chromosome defects, all metaphases abnormal, double or complex chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the multivariate approach, B234 and C23 proved to be significantly associated with a reduction in the survival probability. The similarity of the regression coefficients associated with these two factors means that they have about the same weight. Consequently, the model was simplified by counting the number of factors (0, 1, or 2) present in each patient, thus generating a scoring system called the Lausanne-Bournemouth score (LB score). The LB score combines the well-recognized and easy-to-use Bournemouth score (B score) with the chromosome defect complexity, C23 constituting an additional indicator of patient outcome. The predicted risk of death within 18 months calculated from the model is as follows: 7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1% (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The scoring system presented here has several interesting features. The LB score may improve the predictive value of the B score, as it is able to recognize two prognostic groups in the intermediate risk category of patients with B scores of 2 or 3. It has also the ability to identify two distinct prognostic subclasses among RAEB and possibly CMML patients. In addition to its above-described usefulness in the prognostic evaluation, the LB score may bring new insights into the understanding of evolution patterns in MDS. We used the combination of the B score and chromosome complexity to define four classes which may be considered four possible states of myelodysplasia and which describe two distinct evolutional pathways.

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations.

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Patient versus general practitioner perception of problems with treatment adherence in type 2 diabetes: from adherence to concordance.

OBJECTIVES: To determine the prevalence of problems with treatment adherence among type-2 diabetic patients with regards to medication, dietary advice, and physical activity; to identify the associated clinical and psychosocial factors; and to investigate the degree of agreement between patient-perceived and GP-perceived adherence. METHODS: Consecutive patients were solicited during visits to 39 GPs. In total, 521 patients self-reported on treatment adherence, anxiety and depression, and disease perception. The GPs reported clinical and laboratory data and patients' adherence. A multivariate analysis identified the factors associated with adherence problems. RESULTS: Problems of adherence to medication, dietary advice, and physical activity recommendations were reported by 17%, 62%, and 47% of the patients, respectively. Six independent factors were found associated with adherence problems: young age, body-mass index (BMI) > 30 kg/m(2), glycosylated haemoglobin (HbA(1c)) > 8%, single life, depression, and perception of medication as a constraint. Agreement between patients' and GPs' assessments of treatment problems reached 70%. CONCLUSION: In type 2 diabetes, problems with dietary advice or physical activity are far more frequent than problems with medication, and not all physicians are fully aware of patients' problems. More active listening and shared decision-making should enhance adherence and improve outcomes.

Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

Description of a tertiary swiss university hospital palliative population based on the International Classifiaction of Disease (ICD) : a retrospective pilot study

Introduction : L'équipe mobile de soins palliatifs intra hospitalière (EMSP) du Centre Hospitalier Universitaire Vaudois (CHUV) a été mise en place en 1996. Il s'agit d'une des premières équipes interdisciplinaire de consultants mise à disposition d'un hôpital tertiaire. Le CHUV est l'hôpital de proximité de la ville de Lausanne (850 lits) mais aussi un hôpital de référence pour le reste du canton. En 2007, il y a eu 38'359 patients hospitalisés au CHUV. Les facteurs d'évaluation du taux d'utilisation d'une équipe mobile de soins palliatifs consultantes sont variés et complexes. Plusieurs méthodes sont décrites dans la littérature pour tenter de répondre à cette problématique. Avant de pouvoir évaluer l'utilisation de notre équipe mobile consultante de soins palliatifs intra hospitalière, il nous est apparu nécessaire de mieux décrire et définir la population qui meurt dans notre institution. McNamara et collègues ont proposé des critères qui classifient une population palliative comme « minimale », « intermédiaire » ou « maximale ». L'objectif de cette étude est de déterminer le taux de patients décédés au CHUV sur une période de 4 mois (Γ1 février au 31 mai 2007) suivie par notre EMSP en utilisant la méthode de classification «minimal » et « maximal ». Méthode : les archives médicales du CHUV ont été analysées pour chaque patient adulte décédé pendant la période sélectionnée. Les populations « maximal » et « minimal » de ces patients ont été ensuite déterminées selon des critères basés sur les codes diagnostiques figurants sur les certificats de décès. De ces deux populations, nous avons identifié à partir de notre base de données, les patients qui ont été suivie par notre EMSP. Le CHUV utilise les mêmes codes diagnostiques (International Classification of Disease, ICD) que ceux utilisés dans la classification de McNamara. Une recherche pilote effectuée dans les archives médicales du CHUV manuellement en analysant en profondeur l'ensemble du dossier médical a révélé que la classification de la population « minimal » pouvait être biaisée notamment en raison d'une confusion entre la cause directe du décès (complication d'une maladie) et la maladie de base. Nous avons estimé le pourcentage d'erreur de codification en analysé un échantillon randomisé de patients qui remplissait les critères « minimal ». Résultats : sur un total de 294 décès, 263 (89%) remplissaient initialement les critères « maximal » et 83 (28%) les critères «minimal», l'analyse de l'échantillon randomisé de 56 dossiers de patients sur les 180 qui ne remplissaient pas les critères « minimal » ont révélé que 21 (38%) auraient dus être inclus dans la population « minimal ». L'EMSP a vu 67/263 (25.5%) de la population palliative « maximal » et 56/151 (37.1%) de la population palliative « minimal ». Conclusion : cette étude souligne l'utilité de la méthode proposée par McNamara pour déterminer la population de patients palliatifs. Cependant, notre travail illustre aussi une limite importante de l'estimation de la population « minima » en lien avec l'imprécision des causes de décès figurant sur les certificats de décès de notre institution. Nos résultats mettent aussi en lumière que l'EMSP de notre institution est clairement sous- utilisée. Nous prévoyons une étude prospective de plus large envergure utilisant la même méthodologie afin d'approfondir les résultats de cette étude pilote.

Defining new criteria for selection of cell-based intestinal models using publicly available databases.

BACKGROUND: The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. RESULTS: We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. CONCLUSIONS: This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question.

Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.

La fonction de Moi auxiliaire dans la prise en charge des douloureux chroniques [The role of the auxiliary ego in the care of the chronic pain patient]

La prise en charge des patients souffrant de douleurs chroniques, à l'interface entre corps et psyché, nécessite une approche globale et souvent un réseau de soins coordonnés, contenant et stable. La psychiatrie de liaison a naturellement trouvé sa place dans ce réseau de soins spécifiques auprès des différents soignants impliqués. Les réflexions issues de cette expérience ont pour objectif de mieux comprendre le rôle thérapeutique des soignants et font émerger la notion de Moi auxiliaire comme élément clé dans le traitement de ces patients. Dans cet article, nous reprendrons les fondements historiques et conceptuels de la fonction de Moi auxiliaire pour nous intéresser à ses différentes applications dans ces prises en charge : consultation médicale, psychothérapie individuelle ou de groupe, colloque interdisciplinaire. The management of the patient suffering from chronic pain, situated on the interface between body and psyche, necessitates a global approach and often a coordinated, stable and containing network of care. Liaison psychiatry has become part of this network, together with various health care professionals from somatic disciplines. Based on these experiences, this article aims to better understand the therapeutic role of those who take care of the chronic pain patient by identifying the auxiliary ego as a key element of care. The historical development and conceptual framework of the auxiliary ego are utilized to highlight its roles in the different aspects of care of these patients:in the medical consultation, individual psychotherapy, group psychotherapy and in the interdisciplinary meetings.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

ABSTRACT: BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Iliac wing fracture following graft harvesting from the anterior iliac crest: literature review based on a case report.

The morbidity of bone graft harvesting from the iliac crest has been widely discussed in the literature. For some authors, it is considered to be low and for others relatively high. We report on a case of a fracture of the iliac wing after graft harvesting from the anterior iliac crest despite good surgical technique. This complication is well known and most of these fractures heal uneventfully if treated conservatively. However, if anatomical and technical considerations are respected, the patient could be spared this inconvenience. Based on a literature review, we discuss the procedure's potential complications and how to avoid them in an update.

Systematic review of population pharmacokinetic analyses of imatinib and relationships with treatment outcomes

Several population pharmacokinetic (PPK) analyses of the anticancer drug imatinib have been performed to investigate different patient populations and covariate effects. The present analysis offers a systematic qualitative and quantitative summary and comparison of those. Its primary objective was to provide useful information for evaluating the expectedness of imatinib plasma concentration measurements in the frame of therapeutic drug monitoring. The secondary objective was to review clinically important concentration-effect relationships to provide help in evaluating the potential suitability of plasma concentration values. Nine PPK models describing total imatinib plasma concentration were identified. Parameter estimates were standardized to common covariate values whenever possible. Predicted median exposure (Cmin) was derived by simulations and ranged between models from 555 to 1388 ng/mL (grand median: 870 ng/mL and interquartile "reference" range: 520-1390 ng/mL). Covariates of potential clinical importance (up to 30% change in pharmacokinetic predicted by at least 1 model) included body weight, albumin, α1 acid glycoprotein, and white blood cell count. Various other covariates were included but were statistically not significant or seemed clinically less important or physiologically controversial. Concentration-response relationships had more importance below the average reference range and concentration-toxicity relationships above. Therapeutic drug monitoring-guided dosage adjustment seems justified for imatinib, but a formal predictive therapeutic range remains difficult to propose in the absence of prospective target concentration intervention trials. To evaluate the expectedness of a drug concentration measurement in practice, this review allows comparison of the measurement either to the average reference range or to a specific range accounting for individual patient characteristics. For future research, external PPK model validation or meta-model development should be considered.