Enhancing cognition before clinical symptoms of dementia.

As the title of the special issue indicates, controversy surrounds augmentation of brain cognition in humans. Lacking efficacious drugs for Alzheimer's disease (AD) and with many AD patients recruited for clinical trials that unfortunately do not provide the expected results, one wonders whether to test cognition enhancement strategies in individuals without symptoms of cognition decline. This opinion article presents the view that safe drugs and or dietary supplements should be tested worldwide in aged individuals under the control of a non-for-profit organization.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

Clinical features of oral lichen planus. A retrospective study of 65 cases

Objectives: To describe the clinical features of patients diagnosed with oral lichen planus (OLP) and to establish the prevalence of its malignant transformation in our setting. Study design: A retrospective study was made of 65 patients clinically and histologically diagnosed with OLP in the Service of Oral Surgery (Dental Clinic of the University of Barcelona, Spain) in the period 1990-2005. A descriptive and bivariate statistical analysis was made. Results: The mean patient age was 59 years (SD ± 14.9). Most of the patients (61%) were women, and the most frequent location of the lesions was the buccal mucosa (90.8%). White forms of OLP were noted in 66% of the cases, and 46.2% of the patients reported symptoms of some kind. The patients diagnosed with diabetes mellitus (20%) showed a larger proportion of red lesions (p=0.088). No statistically significant association was observed between chronic liver disease and the OLP lesion types or symptoms. Two cases of squamous cell carcinoma were identified in two patients previously or simultaneously diagnosed with OLP. A statistically significant correlation was observed between dysplastic changes / malignization of the lesions and smoking habit (p=0.019). An association to alcohol abuse was also noted, though in this case statistical significance was not reached (p=0.085). Conclusions: The clinical features of our study population were similar to those described in other studies. Diabetic patients with OLP were seen to be more susceptible to the development of atrophic-erosive lesions. Smokers and/or patients with alcohol abuse in turn showed a greater tendency to develop dysplastic changes / malignization in the histopathological study of the lesions

Temperamental Dimension and Anxiety Problems in a Clinical Sample of Three- to Six-year old Children: A Study of Variables

In the last few years, many researchers have studied the presence of common dimensions of temperament in subjects with symptoms of anxiety. The aim of this study is to examine the association between temperamental dimensions (high negative affect and activity level) and anxiety problems in clinicalpreschool children. A total of 38 children, ages 3 to 6 years, from the Infant and Adolescent Mental Health Center of Girona and the Center of Diagnosis and Early Attention of Sabadell and Olot were evaluated by parents and psychologists. Their parents completed several screening scales and, subsequently, clinical child psychopathology professionals carried out diagnostic interviews with children from the sample who presented signs of anxiety. Findings showed that children with high levels of negative affect and low activity level have pronounced symptoms of anxiety. However, children with anxiety disorders do not present different temperament styles from their peers without these pathologies

The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia.

Background: Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs) on cognitive performance over time. Methods: In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13) or novel antipsychotics (n = 26) at baseline and at two years after. Results: Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

Spectrum of gluten sensitive enteropathy in first degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II¿III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p=0.002). Marsh I relatives had more severe abdominal pain (p=0.006), severe distension (p=0.047) and anaemia (p=0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Construction of a scale to evaluate the diurnal impact of insomnia

The objective of this study was to develop and validate a scale to assess the diurnal impact of insomnia. The Insomnia Diurnal Impact Scale (IDIS) comprises six items designed to evaluate the daytime effects of insomnia. The sychometric properties of the original scale were analysed in a sample of 172 students, while its ability to differentiate insomniacs and non-insomniacs (according to the International Classification of Diseases (ICD)-10 criteria) was examined in a sample of 79 psychiatric patients and 82 individuals from the community. The psychometric properties of the English version were then analysed in a sample of 44 Englishspeaking participants. The results showed the internal consistency coefficient to be very good (0.86), with testretest reliability at 1 month being 0.79. A single factor explained almost 60% of the variance. Correlation of the IDIS with other scales varied between moderate and high values. Sensitivity was 78% and specificity 57% in the community sample, while the corresponding figures for the psychiatric population were 83% and 63%. Cronbach's ¿ coefficient for the English version reached a value of 0.93. These results indicate that the IDIS shows adequate reliability and validity with both general and psychiatric populations, and also that it can discriminate between the presence and absence of insomnia. The English version presents good preliminary results regarding item-corrected total correlation and internal consistency. In conclusion, the IDIS appears to be a useful tool in the primary care and mental health contexts for assessing insomnia-related diurnal dysfunction.

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download

The metabolic syndrome, a multifaceted disease of affluence

Metabolic syndrome developed in consequence of an evolutionary inadequacy: the human body was unprepared for a dietary excess of nutrients, especially lipids (largely in detriment of carbohydrate). This excess awakens metabolic signals akin to those of starvation, in which the main energy staple is the body"s own lipid reserve. Lipid dietary abundance prevents the use of glucose, which in turn limits the oxidation of amino acids. To ward against a subsequent avalanche of substrates, the immune system and hypertrophied tissues (for example, adipose) elicit a series of defence responses. This response is probably the ultimate basis of a disease that is manifested as various pathologies, which were initially defined as distinct entities but which are slowly being seen as a single pathognomic unit in the literature. Based on their common origin of the ample availability of food in our modern society, the cluster of diseases comprising the metabolic syndrome is probably best described as a single multifaceted disease.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Dimensional structure of the Brief Symptom Inventory with Spanish College students.

The Brief Symptom Inventory is designed to assess symptoms of psychological disorders in adolescents and adults. The dimensional structure of the inventory, using exploratory and confirmatory factor analyses, was examined with a cross-sectional design in a Spanish sample of college students (N = 1,033, aged between 18 and 30 years old). Two hypotheses were tested: the original distribution of the items in nine factors, and the unidimensionality of the inventory. According to the results, a nine-factor structure seemed to be confirmed, although the strong intercorrelations found among the subscales indicated that these were measuring closely related constructs. The importance of cultural influences when assessing psychological symptoms and the need to develop national and sex norms for instruments that assess psychopathology, are also discussed.

Systems Medicine and Integrated Care to Combat Chronic Noncommunicable Diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Review and new therapeutic alternatives for the treatment of cutaneous Leishmaniasis

Leishmaniasis comprises a group of diseases caused by protozoa of the genus Leishmania and has two basic clinical forms, visceral Leishmaniasis and cutaneous Leishmaniasis. The clinical features of Leishmaniasis depend on the species of Leishmania, the interaction between host and parasite and the immune response. This work focuses on cutaneous leishmaniosis because although it is not a deadly disease it results in significant scars and facial disfigurements, thus being clinically important. Furthermore, the first-line treatment consists of intravenous or intramuscular administration of intralesional pentavalent antimonials, which are highly toxic, making hospitalization of patients compulsory during treatment, with the associated financial costs. Herein, we review studies on drugs and treatments with fewer side effects and easier routes of administration such as topical administration. Recent research shows that the topical route of administration holds promise for the future treatment of cutaneous leishmaniosis.