Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.

Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.

Prevalence and awareness of cardiovascular risk factors in patients with schizophrenia: a cross-sectional study in a low cardiovascular disease risk geographical area.

OBJECTIVE: Prevalence of cardiovascular disease is high in schizophrenia. Our aim is to estimate the prevalence of cardiovascular risk factors (CVRF) among schizophrenia patients. METHOD: National cross-sectional study in patients diagnosed with schizophrenia under treatment with second generation antipsychotics and admitted to short-stay hospitalisation units. RESULTS: A sample of 733 consecutively admitted patients was enrolled; the most prevalent CVRFs were smoking 71% (95% CI: 67-74%) and hypercholesterolemia 66% (61-70%) followed by hypertriglyceridemia 26% (26-32%), hypertension 18% (15-21%) and diabetes 5% (4-7%). Metabolic syndrome showed 19% (95% CI: 16-23%) prevalence or, according to updated definitions (Clin Cornerstone 7 [2005] 36-45), 24% (95% CI: 20-28%). The rate of patients within the high-risk range of a 10-year fatal cardiovascular event was 6.5%. CVRFs under routine management were diabetes (60%), hypertension (28%) and, to a lesser extent, dyslipemia (14%). Treatment for CVRFs was associated to gender, men for hypertension OR = 25.34, p < 0.03 and women for diabetes OR = 0.02, p < 0.03. CONCLUSION: We found that CVRFs in schizophrenia were prevalent and under-diagnosed, and thus with insufficient therapeutic management.

Talus fractures. Functional results for polytraumatized patients. / Fracturas de astrágalo. Resultados funcionales en pacientes politraumatizados.

Talar fractures are uncommon lesions (0.1-0.9%) and have a high rate of complications. One of the situations in which a fracture of the talus can occur is in the context of polytrauma which may further compromise the functional prognosis. The aim of this study was to analyze the functional results in patients with talar fractures whether or not they occurred in the context of polytrauma. Observational study on a retrospective cohort of 24 patients operated in our centre (2008-2016). They were grouped according to whether they were polytraumatized (ISS>16) or not (ISS≤16). Review of sociodemographic, radiographic, functional variables (VAS pain scale and FADI -Foot and Ankle Disability Index-) and the onset of complications such as arthrosis, arthrodesis or avascular necrosis. Review of 25 talar fractures in 24 patients with a mean age of 38 years (19-75) and a mean follow-up of 4.2 years (0.5-9). According to the ISS, 44% of patients (11) were polytraumatized and 56% (14) were not. The average score according to the FADI scale was 62 points for the polytraumatized patients and 76.9 for the non-polytraumatized patients. The pain according to the VAS scale was 5.8 points in the group of polytraumatized patients and 4.3 in the non-polytraumatized patient group. Regarding complications, 64% of the polytraumatized patients and 43% of the non-traumatized patients had a complication. 36% of the polytraumatized patients had clinical and radiological signs of subtalar arthrosis compared to 35% of the non-traumatized patients, of whom 27% underwent arthrodesis compared to 28% of the non-traumatized patients. 27% of the polytraumatized patients were diagnosed with avascular necrosis as opposed to 0% of the non-polytraumatized patients.

Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial.

BACKGROUND: Paliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism. METHODS: The efficacy and safety of once-daily paliperidone ER (6 mg, 9 mg and 12 mg) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. RESULTS: All doses of paliperidone ER demonstrated significant improvement in PANSS score, all PANSS Marder factor scores (p<0.001) and personal and social functioning versus placebo (p<0.001). The PANSS total score also improved significantly in the olanzapine treatment arm. Significantly higher percentages of paliperidone ER patients demonstrated a > or =30% reduction in PANSS total score versus placebo (p<0.001). The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups. In the paliperidone ER groups there were no reports of glucose-related AEs or clinically relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg. CONCLUSION: In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia.

Evaluating the appropriateness of digoxin level monitoring.

BACKGROUND: Digoxin level determinations can be useful clinically in patients receiving digoxin therapy but are sometimes misused. METHODS: Explicit appropriateness criteria were adapted from previously published criteria and revised using local expert opinion. They were then used to evaluate the appropriateness of random samples of inpatient and outpatient serum digoxin levels. Overall agreement between reviewers regarding appropriateness was good (K = 0.65). Patients in the study included 162 inpatients in whom 224 digoxin levels were measured and 117 outpatients in whom 130 digoxin levels were measured during a 6-month period. The main outcome measure was the proportion of digoxin levels with an appropriate indication. RESULTS: Among inpatient levels, only 16% (95% confidence intervals [CI], 11%-20%) were appropriate. Of the 189 digoxin levels considered inappropriate, only 26 (14%) had a result of 2.3 nmol/L or more (> or =1.8 ng/ mL). None of these levels resulted in an important change in therapy, and no patient had a toxic reaction to the therapy. Among inappropriate levels, daily routine monitoring accounted for 78%. Of the 130 outpatient levels, 52% (95% CI, 44%-61%) were appropriate. Of 62 inappropriate levels, only 4 (6%) had a result of 2.3 nmol/L or more (> or =1.8 ng/mL). One result led to a change in therapy, but none of the patients were believed to experience a toxic reaction. Among the inappropriate levels, 87% of patients underwent early routine monitoring before a steady state was achieved. CONCLUSIONS: A high proportion of digoxin levels were inappropriate, particularly among inpatients. In both groups, the primary reason tests were judged inappropriate was early routine monitoring. Few inappropriate tests resulted in important data. Interventions to improve the use of digoxin levels could potentially save substantial resources without missing important clinical results.

Phospholipids and sialic acid changes produced by vitamin D3 on intestinal mitochondria.

Vitamin D3 administration to vitamin D-deficient chicks produces, 24 hours after treatment, a large increment of phospholipids in mitochondria from intestinal mucosa. Proportion of the different phospholipid classes and fatty acid composition of the organelles were not modified by that treatment. A time course study of the effects of 1,25(OH)2D3 on calcium absorption and sialic acid content of intestinal mitochondria glycoproteins showed that both effects were correlated. The results suggest that either vitamin D or the increase of calcium transfer are involved in the make up of intestinal mitochondria membranes.

Distinct quality of depressed mood: an attempt to develop an objective measure.

Since the time of Kraepelin, in continental Europe the sadness of depression has been considered to have a "distinct quality' basic to the diagnosis of pathological depression. This distinct quality has been interpreted by observers but patients have been noted to have difficulty verbalizing differences from normal sadness. The authors have used a discriminant analysis to study how patients define pathological sadness and as a result have developed a Pathological Sadness Index with a sensitivity of 0.94, a specificity of 0.96 and a total misclassification rate of 5% (kappa w = 0.90).

Sustaining short-term gains for future progress.

Management of patients with acute psychosis represents a considerable challenge for many reasons. As acute psychosis is considered to be a psychiatric emergency that requires immediate and effective intervention, pharmacotherapy with antipsychotic drugs is the mainstay of treatment. The key treatment goals are to calm the agitated, assaultive, violent or disruptive patient, to minimize the danger to self and others and to achieve a smooth transition from intramuscular to oral maintenance treatment with mimimal side-effects. In most circumstances intramuscular formulations of antipsychotic drugs are the optimal treatment choice. However, only the conventional antipsychotics are currently available as intramuscular formulations and unfavourable tolerability profiles reduce the benefit/risk ratio and may make future transition to oral treatment problematic. An intramuscular formulation of an atypical antipsychotic medication would have significant advantages, not only during the acute psychotic phase but also during transition to oral maintenance treatment by enabling an effective and well-tolerated changeover from intramuscular to oral drug treatment.

Treatment of severely psychotic inpatients with schizophrenia: olanzapine versus other antipsychotic drugs.

Nine hundred and ten schizophrenic inpatients suffering from acute psychotic episodes were included in a naturalistic study. Patients were prescribed treatment with olanzapine (OLZ) or with typical antipsychotic (TYP) drugs. Patients receiving another atypical antipsychotic were excluded. Of the whole sample, 483 (53.4%) were treated with olanzapine and 421 (46.6%) with typical antipsychotics. Three specific subpopulations of greater severity were defined: patients with prominent psychotic symptoms, agitated patients, and patients initially treated with intramuscular (i.m.) medication because of their acute clinical condition. Severity of illness was assessed using the Clinical Global Impression (CGI) scale for severity, the Brief Psychiatric Rating Scale (BPRS) and the Nursing Observational Scale for Inpatient Evaluation. Baseline differences were adjusted per data analysis. The mean change from baseline to endpoint of overall symptomatology (total BPRS score) was significantly greater in the olanzapine group compared to the typical antipsychotic-treated group, both in the sample of patients with prominent positive symptoms (P < 0.001) and in the sample of agitated patients (P =0.015). Significant differences were also found in BPRS positive scores, BPRS negative scores and CGI scores in these two populations. Patients who had received previous i.m. drugs showed no statistically significant differences in symptomatic improvement between both treatments groups, except for a more favourable response of BPRS negative subscores in the olanzapine group (P =0.015). The results suggest that olanzapine may be considered as a first line treatment for severely psychotic inpatients with schizophrenia.

[Hygiene, architecture and autopsy]. / Hygiène, architecture et autopsie.

The 24(th) August 1998 decree related to technical prescriptions applicable to hospital mortuaries, to be enacted as of September 11(th) 2001, compels hospital administrations and involved personnel to consider architectural concepts of autopsy room. Nevertheless, the technical prescriptions of this decree seem to be inadequate because an autopsy room requires specific functional and technical organization such as adequate flooring, adapted air-conditioning system and plumbing and of course appropriate autopsy tables. Due to imminent enactement of accreditation procedures, it is likely that in the near future, autopsies will only be performed in centres combining scientific competence and sanitary requirements.

[Diagnosis of malnutrition in the elderly by dual energy absorptiometry]. / Diagnostic de la dénutrition chez les personnes âgées par l'absorptiométrie biénergétique.

OBJECTIVES: Denutrition is a frequent condition in elderly persons and may have major consequences. A noninvasive investigation, whole body dual energy X-ray absorptiometry, should allow, by direct measurement of body composition, early and reliable diagnosis of denutrition. This study was conducted to elaborate a diagnostic tool using this exam and to test its validity. PATIENTS AND METHODS: A global index of denutrition was proposed combining anthropometric, biological criteria, and the Mini Nutritional Assessment scale. Two agreement analyses were made between classical diagnostic criteria of nutritional status and body fat and fat free mass assessed by anthropometry and absorptiometry. An association between nutritional status and body absorptiometric composition were studied with univariate analysis followed by a multivariate logistic regression model. This model allowed an elaboration of a nutritional absorptiometric index (NAI). RESULTS: One hundred one elderly subjects were included. Twenty-three were considered to be in a state of denutrition. Agreement was poor between anthropometric and biological diagnostic criteria of denutrition. It was good between the different masses assess by anthropometry and absorptiometry. Subjects in a state of denutrition had significantly lower body fat and lower fat free mass. The fat free mass index (fat free mass divided by the square height) and body fat were entered into a logistic model and composed the NAI, which showed good diagnostic validity in terms of specificity and sensitivity. DISCUSSION: Absorptiometry appears to be a simple reliable diagnostic tool for assessing denutrition in elderly persons in routine practice. Further studies are required and should lead to a confirmation of the interest of these absorptiometric indexes.

The cost-effectiveness of paliperidone extended release in Spain.

BACKGROUND: Paliperidone Extended Release OROS (ER) is a new atypical antipsychotic for the treatment of schizophrenia. The objective is, based on a previously published model, to analyze the clinical and economic effects of Paliperidone ER in a Spanish setting compared to olanzapine oral and aripiprazole. METHODS: An existing discrete event simulation model was adapted to reflect the treatment of schizophrenia in Spain in terms of costs, resource use, and treatment patterns. Inputs for the model were derived from clinical trial data, literature research, database analysis and interviews with local clinical experts. The time horizon is 5 years and Spanish discount rate was applied. Outputs include direct medical costs and Quality Adjusted Life-Years (QALYs). Extensive sensitivity analyses were carried out to assess the robustness of the results, using ordinary least squares analysis and cost-effectiveness scatter plots. RESULTS: The results show that the mean incremental QALYs (95% CI) compared to olanzpine is 0.033 [-0.143, 0.304] and compared to aripiprazole 0.029 [-0.107, 0.300]. The corresponding mean incremental costs and corresponding confidence intervals are -€1425 [-€10,247, €3084] and -€759 [-€10,479, €3404], respectively. The probability that paliperidone ER is cost-saving and health gaining compared to olanzapine and aripiprazole is 76% and 72%, respectively. Paliperidone ER was estimated to have 80% and 81% probability of being cost-effective compared to olanzapine at a willingness to pay of €20,000 and €30,000 and 73% and 74% compared to aripiprazole, respectively. LIMITATIONS: Some of the modeled inter-relationships had to be based on expert opinion due to a lack of information. Also, foreign sources for the disutility of adverse events had been used due to a lack of Spanish data. Prolactin-related side-effects, indirect costs, and potential compliance advantages of paliperidone ER were not considered. It is unlikely that these limitations affected the conclusions. CONCLUSION: Based on differences in drug acquisition costs, side-effects, and risk of relapse, the model predicts that, in the Spanish healthcare setting, paliperidone ER dominates oral olanzapine and aripiprazole, with a probability of 76% and 72%, respectively.

Country differences in patient characteristics and treatment in schizophrenia: data from a physician-based survey in Europe.

Schizophrenia is a frequent psychiatric disorder whose prevalence appears to be relatively stable across different patient groups. However, attitudes to care and resources devoted to mental health care may differ between countries. The objective of this analysis was to compare sociodemographic and psychopathological features of patients, antipsychotic treatment and frequency of hospitalisation between four European countries (Germany, Greece, Italy and Spain) collected as part of a large survey of the characteristics of patients with schizophrenia. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients. Information on 39 variables was collected. A number of between-country differences were observed which tended to distinguish Germany on the one hand, from the Mediterranean countries, and Greece in particular, on the other. While demographic features and clinical features were essentially similar, more patients in Germany were considered to have severe disease by their psychiatrist (59.0% versus 35.9% in Greece) and to be hospitalised (49.3% versus 15.0%). 46.7% of German patients were living alone compared to less than 20% in the Mediterranean countries and 50.2% were living with their family (versus over 70% elsewhere). Smoking and addictive behaviours were more frequently reported for patients in Spain. With regard to empirically derived patient subgroups, Subgroup 2, corresponding to well-integrated and autonomous patients with mild to moderate disease severity was most highly represented in Greece (23.6% of patients compared to less than 10% elsewhere) elsewhere, Subgroup 6 (poorly-integrated patients with moderately severe disease who require caregiver support) was under-represented in Germany (4.5% versus over 17% elsewhere). Patterns of treatment were essentially similar, although quetiapine was more frequently prescribed and paliperidone less frequently prescribed in Germany than elsewhere. Reasons for treatment choice were comparable between countries, primarily related to good tolerability and control of positive symptoms. The differences observed may be attributed to differences in mental health care resource provision, socio-cultural or educational differences or to resource issues.

Individualizing antipsychotic treatment selection in schizophrenia: characteristics of empirically derived patient subgroups.

Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia.

Treatment adherence in schizophrenia. Spanish clinical consensus.

Objective. Establish a Spanish Consensus on Therapeutic Compliance in Schizophrenia.

Material and methods. An experts committee designed a specific questionnaire having 40 questions and 293 options. The questions referred to the definition and general assessment of compliance in schizophrenia, factors involved, intervention strategies in outpatients and in acute units and management of oral and long duration injectable antipsychotic drugs and other non-pharmacological therapies. First, second or third line strategy values of choice were assigned according to the answers obtained for each item. The questionnaire was sent to 383 psychiatrists of a Therapeutic Compliance Work Group. A total of 326 answers were received with an electronic system that guaranteed their confidentiality.

Results and conclusions. There is maximum agreement on considering the seriousness of the compliance problem, its repercussion in relapses, the patient's course and increase in health care costs. The strategies preferred to evaluate compliance are: counting of the injectable drug administration and determination of plasma concentrations. The Consensus considers that specific intervention is necessary when the patient has already suffered several relapses due to low therapeutic compliance, when null awareness of disease is detected or if there is comorbidity with toxic consumption. Psychoeducational is the non-pharmacological strategy having the greatest consensus grade if intervention is needed. Treatments with atypical injectable, long duration, antipsychotic drugs obtain the best grade in accordance with pharmacological strategies of first choice, in different clinical situations to avoid or improve therapeutic adherence.

Key words:
Adherence. Compliance. Schizophrenia. Consensus.

[Sporotrichoid cutaneous infection by Mycobacterium haemophilum in an AIDS patient]. / Infección cutánea esporotricoide por Mycobacterium haemophilum en un paciente con sida.

We report a case of primary cutaneous infection by Mycobacterium haemophilum after the bite of an aquarium fish in a severely immunodepressed AIDS patient. Clinical features consisted in nodular and ulcerative lesions that followed a sporotrichoid pattern. Histological study of nodular lesions showed a granulomatous dermatitis with numerous acid-fast bacilli. The mycobacterium was identified 3 months later by genetic hybridization from a cultive in solid medium. Combined therapy with isoniazid, rifampin, clarithromycin, ethambutol, amikacin and ciprofloxacin resulted in complete resolution of the lesions. Infection by Mycobacterium haemophilum is a rare mycobacteriosis that usually affects immunodepressed patients. The most common clinical manifestations are cutaneous lesions but the development of sporotrichoid nodular lymphangitis is exceptional.

[Treatment adherence in schizophrenia. A comparison between patient's, relative's and psychiatrist's opinions]. / Adherencia terapeutica en la esquizofrenia: una comparacion entre las opiniones de pacientes, familiares y psiquiatras.

INTRODUCTION: Patients with psychiatric illness typically have great difficulty following a medication regimen, but they also have the greatest potential for benefiting from adherence. Due to the lack of insight in schizophrenia, adherence to treatment is especially important. We try to analyze and compare the opinion on adherence and compliance of psychiatrists, patients with schizophrenia and relatives. METHOD: A direct, anonymous survey specifically designed for the project was administered to psychiatrists, patients and relatives from all over Spain through different associations of patients and family legally constituted in Spain. Analysis was done separately for variables corresponding to the three groups. RESULTS: The psychiatrists (n = 844) considered that 56.8 % of their evaluated patients (n = 7.439) were noncompliers in the past month, as opposed to 43.2% of these patients who were considered good compliers (3,215 patients). Ninety-five percent of the patients (n = 938) stated that they took their medication regularly, while 5 % answered no to this question. Eighty-two percent of relatives (n = 796) think that patients regularly take their medication, but 47% state that they sometimes forget to take it. CONCLUSIONS: Treatment adherence should be evaluated in clinical trials and in research on treatment of diseases, particularly in chronic mental diseases such as schizophrenia. It seems clear that only programs aimed at detection and resolution of the problems involved in treatment adherence will be able to improve the mid- and long-term prognosis of patients with schizophrenic disorders.

Effect of dietary phosphate on intestinal calcium and phosphate absorption.

Intestinal Ca and P absorption was investigated on rachitic chicks raised on diets with a 1% Ca and 0.3% or 1% P contents. 45Ca and 32P absorption was determined by the technique of the isolated gut sac in vivo. In addition, 32P transport was also measured by the everted gut sac procedure in vitro. Treatment with vit. D3 during 7 days increased the 45Ca absorption in animals fed diets containing 0.3% or 1% P. 32P absorption showed an increase after 2 days of treatment and a decrease afterwards. The reduction of 32P absorption was larger in animals fed diet with 1% P. Study of 32P transport with the everted gut sac technique showed an increase after vit. D3 and a loss of intracellular P, regardless the duration of treatment.

Vitamin D3 administration increases the membrane fluidity of intestinal mitochondria.

The fluorescence anisotropy in the mitochondria from vitamin D-treated chicks is significantly lower than that from the vitamin D-deficient animals with the inner core probe DPH. Surface membrane fluidity, measured with the probe TMA-DPH, shows no differences between the organelles of both groups. The fluorescence studies performed in mitochondrial subfractions revealed that cholecalciferol treatment induces a decrease of lipid order parameter S (DPH) in the mitochondrial inner membrane. These results pose the question of whether vitamin D3 participates in the regulation of physiological function of the intestinal mitochondria through changes in the physical properties of the membranes.