Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations.</p> <p>Methods</p> <p>A literature search was conducted using the <it>Medline</it>, <it>Embase </it>and <it>International Pharmaceutical Abstracts </it>databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems.</p> <p>Results</p> <p>Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies.</p> <p>Conclusions</p> <p>Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.</p

Evaluating an integrated neighbourhood approach to improve well-being of frail elderly in a Dutch community: a study protocol

<p>Abstract</p> <p>Background</p> <p>An important condition for independent living is having a well-functioning social network to provide support. An Integrated Neighbourhood Approach (INA) creates a supportive environment for the frail elderly, offering them tailored care in their local context that allows them to improve self-management abilities and well-being. The purpose of our research is to investigate how an INA can contribute to outcomes of frail elderly and the cost-effectiveness of such a program. The first central study question is: To what extent does INA contribute to (a) continuous, demand-driven, coordinated care and support for the independently- living frail elderly; (b) improvement of their well-being and self-management abilities; and (c) reinforcement of their neighbourhood networks. The second central research question is: is the INA a cost-effective method to support the frail, independently- living elderly?</p> <p>Methods</p> <p>We investigate a Dutch INA. This transition experiment aims to facilitate the independently-living frail elderly (70+) to live the life they wish to live and improve their well-being. The study population consists of independently-living frail elderly persons in Rotterdam. The transition experiment starts in two Rotterdam districts and is later extended to two other districts. We propose a concurrent mixed methods design, that is, a combination of qualitative and quantitative research methods to evaluate processes, effects and costs of INA. Such a design will provide insight into an on-going INA and demonstrate which of its elements are potentially (cost)-effective for the frail elderly.</p> <p>Discussion</p> <p>We embrace a wide range of scientific methodologies to evaluate the INA project and obtain information on mechanisms and contexts that will be valuable for decision making on local and national levels. The study will lead to a better understanding of how to provide support via social networks for the frail elderly and add to the knowledge on the feasibility and cost-effectiveness of the program in maintaining or improving their well-being. Last, the study will highlight the factors that determine the program's success or failure.</p

Alcohol use and misuse: What are the contributions of occupation and work organization conditions?

<p>Abstract</p> <p>Background</p> <p>This research examines the specific contribution of occupation and work organization conditions to alcohol use and misuse. It is based on a social-action model that takes into account agent personality, structures of daily life, and macro social structures.</p> <p>Methods</p> <p>Data come from a representative sample of 10,155 workers in Quebec, Canada. Multinomial regression models corrected for sample design effect have been used to predict low-risk and high-risk drinking compared to non-drinkers. The contribution of occupation and work organization conditions (skill used, decision authority, physical and psychological demands, hours worked, irregular work schedule, harassment, unionization, job insecurity, performance pay, prestige) have been adjusted for family situation, social network outside the workplace, and individual characteristics.</p> <p>Results</p> <p>Compared to non-qualified blue-collars, both low-risk and high-risk drinking are associated with qualified blue-collars, semi-qualified white-collars, and middle managers; high-risk drinking is associated with upper managers. For constraints-resources related to work organization conditions, only workplace harassment is an important determinant of both low-risk and high-risk drinking, but it is modestly moderated by occupation. Family situation, social support outside work, and personal characteristics of individuals are also associated with alcohol use and misuse. Non-work factors mediated/suppressed the role of occupation and work organization conditions.</p> <p>Conclusion</p> <p>Occupation and workplace harassment are important factors associated with alcohol use and misuse. The results support the theoretical model conceptualizing alcohol use and misuse as being the product of stress caused by constraints and resources brought to bear simultaneously by agent personality, structures of daily life, and macro social structures. Occupational alcohol researchers must expand their theoretical perspectives to avoid erroneous conclusions about the specific role of the workplace.</p

Pre-post changes in psychosocial functioning among relatives of patients with depressive disorders after Brief Multifamily Psychoeducation: A pilot study

<p>Abstract</p> <p>Background</p> <p>Depressive disorder is often chronic and recurrent, and results in a heavy psychosocial burden on the families of patients with this disorder. This study aims to examine the effectiveness of brief multifamily psychoeducation designed to alleviate their psychosocial burden.</p> <p>Methods</p> <p>Thirty-two relatives of patients with major depressive disorder participated in an open study testing the effectiveness of brief multifamily psychoeducation. The intervention consisted of four sessions over the course of 6 weeks. Outcome measures focused on emotional distress, care burden and Expressed Emotion (EE).</p> <p>Results</p> <p>The emotional distress, care burden and EE of the family all showed statistically significant improvements from baseline to after the family intervention. The proportion of relatives scoring 9 or more on K6, which indicates possible depressive or anxiety disorder, decreased from sixteen relatives (50.0%) at baseline, to only 3 relatives (9.3%) after the intervention.</p> <p>Conclusions</p> <p>This study suggests that brief multifamily psychoeducation is a useful intervention to reduce the psychosocial burden of the relatives of patients with depressive disorder. Further evaluation of family psychoeducation for relatives of patients with depressive disorder is warranted.</p

Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%), and from patients with neurological disorders that may resemble ALS (91%), between two levels of disease severity (90%), and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms

Home medicines reviews following acute coronary syndrome: study protocol for a randomized controlled trial

Background: Despite continual improvements in the management of acute coronary syndromes, adherence to guideline-based medications remains suboptimal. We aim to improve adherence with guideline-based therapy following acute coronary syndrome using an existing service that is provided by specifically trained pharmacists, called a Home Medicines Review. We have made two minor adjustments to target the focus of the existing service including an acute coronary syndrome specific referral letter and a training package for the pharmacists providing the service.Methods/Design: We will be conducting a randomized controlled trial to compare the directed home medicines review service to usual care following acute coronary syndromes. All patients aged 18 to 80 years and with a working diagnosis of acute coronary syndrome, who are admitted to two public, acute care hospitals, will be screened for enrolment into the trial. Exclusion criteria will include: not being discharged home, documented cognitive decline, non-Medicare eligibility, and presence of a terminal malignancy. Randomization concealment and sequence generation will occur through a centrally-monitored computer program. Patients randomized to the control group will receive usual post-discharge care. Patients randomized to receive the intervention will be offered usual post-discharge care and a directed home medicines review at two months post-discharge. The study endpoints will be six and twelve months post-discharge. The primary outcome will be the proportion of patients who are adherent to a complete, guideline-based medication regimen. Secondary outcomes will include hospital readmission rates, length of hospital stays, changes in quality of life, smoking cessation rates, cardiac rehabilitation completion rates, and mortality.Discussion: As the trial is closely based on an existing service, any improvements observed should be highly translatable into regular practice. Possible limitations to the success of the trial intervention include general practitioner approval of the intervention, general practitioner acceptance of pharmacists' recommendations, and pharmacists' ability to make appropriate recommendations. A detailed monitoring process will detect any barriers to the success of the trial. Given that poor medication persistence following acute coronary syndrome is a worldwide problem, the findings of our study may have international implications for the care of this patient group.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12611000452998. © 2012 Bernal et al; licensee BioMed Central Ltd

Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

Background: Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care progra