Treatment of extraintestinal manifestations in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a systemic disease associated with a large number of extraintestinal manifestations (EIM). EIM are present in 15-20% of patients with ulcerative colitis and in 20-40% of patients with Crohn's disease. The management of EIM is best provided by a multidisciplinary team, which includes specialists in the affected organ systems with training in the treatment of IBD. Therapeutic strategy is often empirical. This is explained by the paucity of randomized-controlled studies for the specific treatment of EIM in IBD and by the fact that treatment models are based on extrapolation from patients with similar conditions but without IBD. For most EIM, the mainstay of therapy is the treatment of the underlying active IBD. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis and primary sclerosing cholangitis run a clinical course independent of IBD activity and need specific therapy (e.g. TNF antagonists in ankylosing spondylitis and skin manifestations). This review summarizes the conventional and novel (e.g. anti-TNF) treatment modalities, and the therapeutic implications for the management of extraintestinal symptoms in IBD, in order to assist clinicians in optimizing treatment strategies for IBD patients with EIM.

The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and follow-up of the efficacy of treatment of Fabry disease: a review of the literature.

Fabry disease is caused by a deficiency of a-galactosidase A which leads to the progressive intra-lysosomal accumulation of ceramide trihexoside (CTH), also known as globotriaosylceramide (Gb3), in different cell types and body fluids. The clinical manifestations are multisystemic and predominantly affect the heart, kidney and central nervous system. The role of CTH in the pathophysiological process of Fabry disease is not established, and the link between the degree of accumulation and disease manifestations is not systematic. The use of CTH as a diagnostic tool has been proposed for several decades. The recent introduction of a specific treatment for Fabry disease in the form of enzyme replacement therapy (ERT) has led to the need for a biological marker, in place of a clinical sign, for evaluating the efficacy of treatment and also as a tool for following the long term effects of treatment. The ideal biomarker must adhere to strict criteria, and there should be a correlation between the degree of clinical efficacy of treatment and a change in its concentration. This review of the literature assesses the utility of CTH as a diagnostic tool and as a marker of the efficacy of ERT in patients with Fabry disease. Several techniques have been developed for measuring CTH; the principles and the sensitivity thresholds of these methods and the units used to express the results should be taken into consideration when interpreting data. The use of CTH measurement in Fabry disease should be re-evaluated in light of recent published data.

History of offending behavior in first episode psychosis patients: A marker of specific clinical needs and a call for early detection strategies among young offenders.

OBJECTIVES: Previous literature suggests that early psychosis (EP) patients with a history of offending behavior (HOB) have specific clinical needs. The aims of this study were to assess: (1) the prevalence of HOB in a representative sample of EP; (2) the premorbid and baseline characteristics of patients with HOB, and (3) the potential differences in short-term outcome of such patients when compared to patients without HOB. METHODS: The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 EP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data of 647 patients could be analyzed. RESULTS: HOB patients (29% of the sample) were more likely to be male with lower level of premorbid functioning and education, have used illicit substances and have attempted suicide. They presented with a more complex clinical picture and had poorer 18-month outcome. Most importantly, they had a significantly longer duration of untreated psychosis. CONCLUSIONS: On the basis of the high prevalence and specific features of EP patients with HOB, our study confirms a need for additional research in this domain and for the development of specific treatment strategies. Most importantly, it suggests a need for the promotion of early detection strategies among the populations of young offenders, considering that some of them may be going through the early phases of a psychotic disorder and that reduction of treatment delay and provision of well adapted interventions may have a significant impact at numerous levels in such patients.

Emotional processing in a ten-session general psychiatric treatment for borderline personality disorder: a case study.

This study examines the effects of a borderline-specific treatment, called general psychiatric management, on emotional change, outcome and therapeutic alliance of an outpatient presenting with borderline personality disorder. Based on the sequential model of emotional processing, emotional states were assessed in a 10-session setting. The case showed an increase in expressions of distress and no change in therapeutic alliance and tended towards general deterioration. Results suggest emotional processing may play a lesser role in general psychiatric management in early phase treatment than previously hypothezised. Copyright © 2015 John Wiley & Sons, Ltd.

Neonatal treatment of CINCA syndrome.

ABSTRACT: Chronic Infantile Neurological Cutaneous Articular (CINCA) syndrome, also called Neonatal Onset Multisystem Inflammatory Disease (NOMID) is a chronic disease with early onset affecting mainly the central nervous system, bones and joints and may lead to permanent damage. We report two preterm infants with severe CINCA syndrome treated by anti-interleukin-1 in the neonatal period, although, so far, no experience with this treatment in infants younger than three months of age has been reported. A review of the literature was performed with focus on treatment and neonatal features of CINCA syndrome. CASE REPORT: Two cases suspected to have CINCA syndrome were put on treatment with anakinra in the early neonatal period due to severe clinical presentation. We observed a rapid and persistent decline of clinical signs and systemic inflammation and good drug tolerance. Diagnosis was confirmed in both cases by mutations in the NLRP3/CIAS1-gene coding for cryopyrin. As particular neonatal clinical signs polyhydramnios and endocardial overgrowth are to be mentioned. CONCLUSION: We strongly suggest that specific treatment targeting interleukin-1 activity should be started early. Being well tolerated, it can be introduced already in neonates presenting clinical signs of severe CINCA syndrome in order to rapidly control inflammation and to prevent life-long disability.

Should biomarkers be used to design personalized medicine for the treatment of glioblastoma?

Significant progress has been made in understanding the molecular pathogenesis of gliomas and in predicting general outcome depending on a limited set of clinical parameters and molecular markers. However, methylation of the O⁶-methylguanine DNA methyltransferase (MGMT) gene promoter is the only molecular marker linked to sensitivity of a specific treatment, that is, alkylating agent chemotherapy, and this predictive value may be limited to glioblastoma. Moreover, in the absence of potent alternative drugs, temozolomide chemotherapy should not be withheld from patients with newly diagnosed glioblastoma without MGMT promoter methylation in general practice. In the context of clinical trials, however, irrespective of whether classical cytotoxic drugs, tyrosine kinase inhibitors or antiangiogenic agents are used, tissue should be centrally collected. Appropriate research programs should seek to define enriched patient populations for future trials and ultimately facilitate individualized cancer treatments.

Making SENSE - Sustained Effort Network for treatment of Status Epilepticus as a multicenter prospective registry.

BACKGROUND: Evidence regarding the different treatment options of status epilepticus (SE) in adults is scarce. Large randomized trials cover only one treatment at early stage and suggest the superiority of benzodiazepines over placebo, of intravenous lorazepam over intravenous diazepam or over intravenous phenytoin alone, and of intramuscular midazolam over intravenous lorazepam. However, many patients will not be treated successfully with the first treatment step. A large randomized trial covering the treatment of established status (ESETT) has just been funded recently by the NIH and will not start before 2015, with expected results in 2018; a trial on the treatment of refractory status with general anesthetics was terminated early due to insufficient recruitment. Therefore, a prospective multicenter observational registry was set up; this may help in clinical decision-making until results from randomized trials are available. METHODS/DESIGN: SENSE is a prospective, multicenter registry for patients treated for SE. The primary objective is to document patient characteristics, treatment modalities and in-house outcome of consecutive adults admitted for SE treatment in each of the participating centres and to identify predictors of outcome. Pre-treatment, treatment-related and outcome variables are documented systematically. To allow for meaningful multivariate analysis in the patient subgroups with refractory SE, a cohort size of 1000 patients is targeted. DISCUSSION: The results of the study will provide information about risks and benefits of specific treatment steps in different patient groups with SE at different points of time. Thus, it will support clinical decision-making and, furthermore, it will be helpful in the planning of treatment trials. TRIAL REGISTRATION: DRKS00000725.

Comparison of two osteoporotic fracture management pathways: experience at 1 year

Introduction: Osteoporosis presenting as low-impact fractures to traumatology units is often undiagnosed and under-treated. Results from the Osteocare study in Lausanne (a nurse based intervention, passive pathway) showed that only 19% of patients received management for osteoporosis, and in the literature [1], the rate is between 10-25%. We have evaluated a different management concept, based on the systematic assessment of patients with osteoporotic fractures during and after hospitalization (active pathway). Methods: Inpatients admitted to the Department of Musculoskeletal Medicine for a fragility fracture were identified by a nurse according to a predefined questionnaire and were then clinically evaluated by a doctor. Based on the results, a management plan was proposed to the patients. Patients could choose between follow up either by their GP or by the Centre of Bone Disease of the CHUV. For patients who chose follow-up in our Centre, we assessed their adherence to medical follow-up 1 year inclusion. The results of patients who had been evaluated in our cohort between the 1 November 2008 and the 1 December 2009 were analysed. Results: 573 inpatients received specific management of their osteoporotic fracture over 18 months. The mean age was 77 y (31-99), 81% were women (203 hip fractures, 40 pelvis fractures, 101 arm fractures, 57 vertebral fractures, 63 ankle fractures, and 25 others sites). During the study period, 303 patients received a proposition of a specific treatment. 39 (13%) chose a follow up with the GP, 19 (6%) dead and 245 (81%) preferred a follow up in our Centre. After 1 year, 166 (67%) patients are under follow up in our outpatient clinic. Conclusion: With an active clinical pathway that starts during the hospitalization, consisting on a nursing evaluation followed by a medical consultation by an expert in osteoporosis, the adherence increased from 19% to 67% in terms of follow up. These results lead us to propose a consultation with a doctor experienced in osteoporosis after all osteoporotic fractures.

Antibody-mediated status epilepticus: a retrospective multicenter survey.

Background: In recent years, an increasing number of auto-antibodies (AB) have been detected in the CSF and serum of patients with new onset epilepsy. Some of these patients develop convulsive or nonconvulsive status epilepticus (AB-SE), necessitating intensive medical care and administration of multiple antiepileptic and immunomodulatory treatments of uncertain effectiveness. Objectives: In this retrospective multicenter survey we aimed to determine the spectrum of gravity, the duration and the prognosis of the disorder. In addition, we sought to identify the antibodies associated with this condition, as well as determine whether there is a most effective treatment regime. Methods: 12 European Neurology University Clinics, with extensive experience in the treatment of SE patients, were sent a detailed questionnaire regarding symptoms and treatment of AB-SE patients. Seven centers responded positively, providing a total of 13 patients above the age of 16. Results: AB-SE affects mainly women (12/13, 92%) with a variable age at onset (17-69 years, median: 25 years). The duration of the disease is also variable (10 days to 12 years, median: 2 months). Only the 3 oldest patients died (55-69 years). Most patients were diagnosed with anti NMDAR encephalitis (8/13) and had oligoclonal bands in the CSF (9/13). No specific treatment regimen (antiepileptic, immunomodulatory) was found to be clearly superior. Most of the surviving 10 patients (77%) recovered completely or nearly so within 2 years of index poststatus. Conclusion: AB-SE is a severe but potentially reversible condition. Long duration does not seem to imply fatal outcome; however, age older than 50 years at time of onset appears to be a risk factor for death. There was no evidence for an optimal antiepileptic or immunomodulatory treatment. A prospective multicenter study is warranted in order to stratify the optimal treatment algorithm, determine clear risk factors of unfavorable outcome and long-term prognosis.

Prophytaxie de l'ostéoporose cortisonique: qui, quand et quoi [Prevention of cortisone-induced osteoporosis: who, when and what?]

Glucocorticoid-induced osteoporosis is a known phenomenon with already an increased fracture risk at 2.5 mg of prednisone daily over 3 months. This risk appears to be independent of bone densitometry results, in contradiction with published guidelines. With the creation of our Department of Musculoskeletal Medicine, we wanted to edict clear recommendations for the prevention of steroid-induced osteoporosis. In addition to the standard general measures to prevent osteoporosis and calcium and vitamin D supplementation, we advocate the use of a specific treatment for osteoporosis in all cases when the duration of corticosteroid therapy is not strictly limited and shorter than 3 months. Bisphosphonates are the treatment of choice, while the analogue of parathyroid hormone remains an alternative in cases with a very high fracture risk.

Acute pain in adults admitted to the emergency room: development and implementation of abbreviated guidelines.

AIM: Although acute pain is frequently reported by patients admitted to the emergency room, it is often insufficiently evaluated by physicians and is thus undertreated. With the aim of improving the care of adult patients with acute pain, we developed and implemented abbreviated clinical practice guidelines (CG) for the staff of nurses and physicians in our hospital's emergency room. METHODS: Our algorithm is based upon the practices described in the international literature and uses a simultaneous approach of treating acute pain in a rapid and efficacious manner along with diagnostic and therapeutic procedures. RESULTS: Pain was assessed using either a visual analogue scale (VAS) or a numerical rating scale (NRS) at ER admission and again during the hospital stay. Patients were treated with paracetamol and/or NSAID (VAS/NRS <4) or intravenous morphine (VAS/NRS > or =04). The algorithm also outlines a specific approach for patients with headaches to minimise the risks inherent to a non-specific treatment. In addition, our algorithm addresses the treatment of paroxysmal pain in patients with chronic pain as well as acute pain in drug addicts. It also outlines measures for pain prevention prior to minor diagnostic or therapeutic procedures. CONCLUSIONS: Based on published guidelines, an abbreviated clinical algorithm (AA) was developed and its simple format permitted a widespread implementation. In contrast to international guidelines, our algorithm favours giving nursing staff responsibility for decision making aspects of pain assessment and treatment in emergency room patients.

Urgences rythmiques [Rhythm emergencies]

Arrhythmias have a high incidence in our population, and since the emergence of new methods in electrophysiology, the mechanism of most tachycardias can be identified. This allows not only to progress in the understanding of their pathophysiology but also in the treatment of arrhythmias, either in an emergency situation or in the chronic phase. The goal of this review is to give some therapeutic advice in case of rhythmic emergencies, keeping in mind that any arrhythmia should be subject to a cardiological work-up to seek specific treatment outside the emergency phase. The proposed therapies in this article are the ones which we are used to apply, but they differ depending on the areas. The final goal is to render service to the patients by trying to be as less damaging as possible, knowing that the understanding of the arrhythmogenic mechanism is not always possible. We hope that the little advice this review contains will be of use for the practitioner and for those who are confronted with patients suffering of acute arrhythmia.

Potential value of biliary CEA assay in early detection of colorectal adenocarcinoma liver metastases.

Elevation of the biliary CEA level in patients with liver metastases from colorectal carcinoma has been reported. The aim of this study is to determine the potential value of biliary CEA assay in the early detection of liver metastases. Biliary and serum CEA levels were determined in patients operated on for a colorectal cancer and in control groups. Among 13 patients with liver metastases from colorectal carcinomas, biliary CEA levels were markedly elevated (> 40 ng/ml) in nine, moderately elevated (5-40 ng/ml) in two and normal (arbitrarily defined as < 5 ng/ml) in two. Of 28 patients with primary colorectal carcinoma without detectable hepatic secondaries, three had marked CEA elevation in the bile, 10 had moderate CEA elevation and 15 had normal levels. Among nine patients with non-malignant hepatobiliary pathology, there was one marked biliary CEA elevation, one moderate elevation and seven normal levels. None of the 13 individuals with no identified hepatobiliary pathology had elevated biliary CEA levels. The follow-up of patients with a primary colorectal tumour, no evidence of hepatic secondaries and a biliary CEA elevation is of particular interest. If subsequent appearance of liver metastases is found in such cases, intra-operative biliary CEA assay could be considered a valuable diagnostic test. Further studies will then have to prove the possible benefit of a specific treatment for this group of patients.

Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era.

Symptoms, comorbidity, and clinical course of depression in immigrants: Putting psychopathology in context.

BACKGROUND: Migration is considered a depression risk factor when associated with psychosocial adversity, but its impact on depression's clinical characteristics has not been specifically studied. We compared 85 migrants to 34 controls, examining depression's severity, symptomatology, comorbidity profile and clinical course. METHOD: A MINI interview modified to assess course characteristics was used to assign DSM-IV axis I diagnoses; medical files were used for Somatoform Disorders. Severity was assessed with the Montgomery-Asberg scale. Wherever possible, we adjusted comparisons for age and gender using logistic and linear regressions. RESULTS: Depression in migrants was characterized by higher comorbidity (mostly somatoform and anxiety disorders), higher severity, and a non-recurrent, chronic course. LIMITATIONS: Our sample comes from a single center, and should be replicated in other health care facilities and other countries. Somatoform disorder diagnoses were solely based on file-content. CONCLUSION: Depression in migrants presented as a complex, chronic clinical picture. Most of our migrant patients experienced significant psychosocial adversity before and after migration: beyond cultural issues, our results suggest that psychosocial adversity impacts on the clinical expression of depression. Our study also suggests that migration associated with psychosocial adversity might play a specific etiological role, resulting in a distinct clinical picture, questioning the DSM-IV unitarian model of depression. The chronic course might indicate a resistance to standard therapeutic regimen and hints at the necessity of developing specific treatment strategies, adapted to the individual patients and their specific context.