Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.

Spanish Adaptation of the Dimensional Apathy Scale (DAS) in Amyotrophic Lateral Sclerosis.

Aim: To adapt, translate, and utilize the Dimensional Apathy Scale (DAS) in Amyotrophic Lateral Sclerosis (ALS) to the Spanish population. Method: We recruited 104 ALS patients (67 of their caregivers) and 49 controls. Participants completed the Spanish-translated DAS, Geriatric Depression Scale- Short form. Patients were also administered the ALS Functional Rating Scale-Revised (ALSFRS-R). Caregivers additionally completed the informant/caregiver-rated Spanish-translated DAS. The DAS was translated to Spanish using a back-translation method. Test-retest and internal consistency reliability were examined. Divergent validity was assessed by comparing the DAS with the depression scale (GDS-15). Principal Component Analysis (PCA) was applied to explore the substructure of the Spanish DAS. Results: The internal consistency reliability of self-rated Spanish DAS was 0.72 and of the informant/caregiver-rated Spanish DAS was 0.84. Correlations between self-rated DAS subscales and GDS-15 were not statistically significant, with a good test-retest reliability. PCA analysis showed a similar substructure to the original DAS. ALS patients had significantly higher Initiation apathy than controls. Additionally, ALS patient informant/caregiver-rated DAS Emotional apathy was significantly higher than the self-rated, with no significant differences observed in the Executive and Initiation subscales. No association was found between DAS and functional impairment using the ALS Functional Rating Scale (ALSFRS-R). Conclusion: The Spanish translation of the DAS is valid and reliable for use in assessing multidimensional apathy in the Spanish population. Availability of the Spanish DAS will allow for future research to explore different apathy subtypes and their impact in ALS and other conditions.

Spanish adaptation of the Amyotrophic Lateral Sclerosis Questionnaire ALSAQ-40 for ALS patients.

We studied the cross-cultural Spanish adaptation of the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) to assess the subjective health status in amyotrophic lateral sclerosis (ALS) patients. The ALSAQ-40 questionnaire was adapted and applied to 53 randomly selected ALS patients from different regions in Spain. Reliability assessment and factorial analysis were performed in order to determine the dimensions of the scale. The validation was carried out by means of comparing the ALSAQ-40 with two instruments usually used in the assessment of ALS patients--the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and the McGill's Quality of Life Questionnaire (MQOL), comparing the latter with the emotional dimension of ALSAQ-40. This Spanish adaptation closely resembles the ALSAQ-40 although the emotional dimension is more heterogeneous and there are cluster-gathering Feeding and Communication dimensions. ALSAQ-40 and ALSFRS questionnaires showed a high correlation, as did the emotional dimension of ALSAQ-40 with the Psychological Symptoms, Life Expectancy, Meaningful Existence and the whole score of the MQOL. In conclusion, this Spanish adaptation of ALSAQ-40 is in accordance with the statistical results from the original English version.

Spanish adaptation of the edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen (ECAS).

OBJECTIVE: Adaptation of the ECAS to the Spanish population. METHODS: The ECAS test was adapted and implemented in a random sample of 102 ALS patients. A test-retest reliability of the instrument and internal consistency assessment were carried out. Its convergent validity was determined by comparing the ECAS screen with the ALS Cognitive Behavioural Screen (ALS-CBS), another standard tool. RESULTS: The Spanish adaptation of the ECAS scale preserves the statistical characteristics of the original version. Its analysis revealed a high internal consistency, similar to that of the original version. A significant correlation was found between the ECAS scale and the ALS-CBS, with the highest degree of correlation values shown at the Executive and Lack of empathy domains scales. Additionally, significant differences were observed between the scores obtained in ALS patients and healthy individuals. Furthermore, the analysis of the screen discrimination ability resulted acceptable. CONCLUSION: The results of this study prove that the Spanish adaptation of the ECAS scale preserves the internal consistency and construct validity of its original version.

Self perceived emotional functioning of spanish patients with amyotrophic lateral sclerosis: a longitudinal study.

BACKGROUND: ALS is a neurodegenerative disease of the entire motor system that most frequently ends with respiratory arrest in few years. Its diagnosis and the rapid progression of the motor dysfunctions produce a continued emotional impact. Studies on this impact are helpful to plan adequate psychotherapeutic strategies. OBJECTIVE: To assess and analyze: First: How the patients with ALS perceive their emotional health. Second: The emotional impact of their physical disabilities. Third: The physical disabilities with highest emotional impact. Fourth: The feelings with highest emotional impact. METHODS: Up to 110 Spanish patients with ALS were assessed less than 1 year from diagnosis, then twice more at 6 month intervals, using the ALS Quality of Life Assessment Questionnaire (ALSAQ-40) validated for use in Spanish. Descriptive analysis and correlation between variables were obtained. RESULTS: Worries about the future, of lack of freedom, and of being a burden were prevalent feelings. On average depression was felt only "sometimes." Only 25% of the variations in the emotional state were explained by changes in the physical state at first evaluation, and 16% at the last one. Emotional functioning correlated significantly with the physical disabilities at first and second evaluation, less so at third. Communication disabilities always had the highest impact. Depression at first evaluation and hopelessness at the next two evaluations had the highest emotional impact. Hopelessness did not correlate with any physical disability at the third evaluation. On the whole, emotional dysfunction was self perceived as intermediate (between none and worst), and remained stable at 1 year follow up, in both bulbar and spinal onset patients. CONCLUSIONS: Physical dysfunctions per se have a limited role in patients´ emotional distress. Communication disabilities, as well as feelings of depression at early stages of illness, and of hopelessness later on, had the most impact. This requires their careful therapeutic attention. On average, Spanish patients with ALS cope with their disease, overcoming depression, which is not felt often, and with just mid levels of emotional dysfunction.

Efectividad de la Medicina Natural y Tradicional en los servicios de urgencias / Effectiveness of Natural and Traditional Medicine in emergency departments

Fundamento: el uso de los medios naturales, como métodos terapéuticos en el tratamiento de las enfermedades dolorosas constituye en la actualidad un reto para las ciencias médicas. Objetivo: evaluar la efectividad de la aplicación de la Medicina Natural y Tradicional como método terapéutico en el servicio de urgencias del Hospital General Docente Mártires de Mayarí. Métodos: se realizó un estudio observacional, descriptivo, prospectivo, en pacientes con enfermedades dolorosas en la consulta de Medicina Natural y Tradicional, ubicada en el servicio de urgencias del Hospital General Docente Mártires de Mayarí del referido municipio, de octubre 2013 a marzo del 2014. El universo estuvo constituido por 180 pacientes con afecciones dolorosas que acudieron al servicio y que les fue indicado la aplicación de las diferentes modalidades de la terapéutica alternativa. La muestra no probabilística quedó constituida por 150 pacientes, que cumplieron con los criterios de inclusión establecidos para esta investigación, a los que se les aplicó tratamiento natural. Resultados: el grupo etáreo entre 50 y 60 años constituyó el de mayor incidencia, predominó el sexo masculino, el mayor porciento de pacientes pertenecen al nivel cultural obrero, solo el 20 % de la muestra tuvieron accesibilidad anterior a la terapéutica. La bursitis del hombro fue la enfermedad de mayor incidencia en tanto la moxibustión constituyó la técnica más utilizada. La mayoría de los pacientes tratados tuvieron evolución satisfactoria, su situación inicial se modificó con una única sesión de tratamiento y se recomendó la continuidad terapéutica en su área de salud. Conclusiones: la Medicina Natural y Tradicional es un método cómodo y barato que no requiere grandes recursos para su aplicación, no se reportan complicaciones durante la aplicación del tratamiento y se reduce el consumo de medicamentos al mínimo por parte de los mismos.

Background: the use of natural means, like therapeutic methods in the treatment of painful diseases, is a challenge for medical sciences nowadays. Objective: to asses the effectiveness of the application of Natural and Traditional Medicine as a therapeutic method in the emergency department of Mártires de Mayarí General Teaching Hospital, Mayarí, Holguín. Methods: an observational, descriptive, prospective study was conducted in patients with painful diseases who were seen at the Natural and Traditional Medicine consultation of the emergency department of Mártires de Mayarí General Teaching Hospital, Mayarí, Holguín from October 2013 to March 2014. The universe was composed of 180 patients with painful conditions who underwent the application of different treatments of alternative therapeutics. The non-probabilistic sample was composed of 150 patients who matched the inclusion criteria established for the research. These patients underwent natural treatment. Results: the age group between 50 and 60 years predominated as well as male sex. The greatest percent of patients belonged to the working class. Only the 20 % of the sample had had previous accessibility to the therapeutics. Shoulder bursitis was the disease with the greatest incidence, while moxibustion was the most used technique. Most patients had a satisfactory progress and got better with only one treatment session. It was recommended to continue the treatment in the health area of each patient. Conclusions: Natural and Traditional Medicine is a convenient and cheap method that does not require great resources for its application. Besides, no complications are reported during the treatments and the consumption of medicaments is minimized.

Predicting in-hospital mortality with coronary bypass surgery using hospital discharge data: comparison with a prospective observational study.

INTRODUCTION AND OBJECTIVES: The aim was to determine the usefulness of the hospital discharge Minimum Basic Data Set (MBDS) for predicting in-hospital mortality with coronary bypass surgery by using data from a prospective observational study as a reference. METHODS: The observational study involved collecting data on all patients undergoing first coronary bypass surgery at five hospitals in Catalonia, Spain between November 2001 and November 2003. In addition, data covering the same period and hospitals were obtained from the MBDS for procedure code 36.1. We investigated the concordance between the information from the two data sources and logistic regression was used to derive predictive models for in-hospital mortality. The model derived using MBDS data was validated using data from the prospective observational study and MBDS data for the years 2004-2006. Model validity was evaluated using discrimination and calibration indices. RESULTS: Some 4.1% of cases in the observational study could not be found in the MBDS. The concordance between the two data sources was highly variable and generally low (kappa values ranged from 0.16 to 0.79). The discriminative ability of the MBDS model was equivalent to that of the observational study model (c=0.80 vs. c=0.79), but when the validity of the former was tested using prospective data and MBDS data for 2004-2006, the discrimination c-index decreased to 0.76 and 0.65, respectively, and the calibration worsened significantly (P< .001). CONCLUSIONS: The risk of in-hospital mortality following coronary surgery cannot be accurately evaluated using MBDS data. However, our results indicate that their use as a predictive tool could be improved.

[The estimated incidence and case fatality rate of ischemic and hemorrhagic cerebrovascular disease in 2002 in Catalonia]. / Estimación de la incidencia poblacional y la mortalidad de la enfermedad cerebrovascular establecida isquémica y hemorrágica en 2002.

INTRODUCTION AND OBJECTIVES: The aim of this study was to obtain an estimate of the incidence of cerebrovascular disease (CVD) in the Spanish population in 2002. METHODS: The study involved data on patients aged over 24 years for the year 2002 contained in both the death register and the Minimum Basic Data Set from 65 of the 84 Catalan general hospitals (i.e., 90.7% of all acute hospital beds in Catalonia). Total and age-adjusted mortality rates, cumulative incidence, and hospitalization rates, and the 28-day case fatality rate for CVD in the Catalan population were calculated after cases of traumatic and transient disease had been excluded. RESULTS: The unadjusted CVD mortality rate per 100,000 population aged over 24 years in Catalonia was 92 in men and 119 in women. The age-adjusted rates were 58 (95% confidence interval or CI, 56-61) and 43 (95% CI, 41-44), respectively. The cumulative incidence of CVD per 100,000 population was 218 (95% CI, 214-221) in men and 127 (95% CI, 125-128) in women. The unadjusted 28-day case fatality rate in the population was 36.2%: 30.3% in men and 42.0% in women. Some 62.5% of patients (57.2% of men and 66.4% of women) died from CVD outside hospital. CONCLUSIONS: These findings indicate that CVD mortality and incidence rates in Catalonia are among the lowest in developed countries. More than half of the deaths that took place within 28 days after the onset of symptoms occurred outside hospital.