In patient stroke rehabilitation efficiency: Influence of organization of service delivery and staff numbers

<p>Abstract</p> <p>Background</p> <p>Outcomes of inpatient stroke rehabilitation need to be reviewed in terms of optimal resource utilization (staff time, service organization, and duration of stay). We compared FIM efficiency scores between three hospitals, and also variation in FIM scores over a ten year period in one hospital undergoing reduction in staff numbers, to examine the relationship between outcome and service characteristics.</p> <p>Method</p> <p>This is a retrospective study comparing the mean FIM efficiency for stroke patients (FIM score – FIM admission score) divided by duration of stay for 2005 among three rehabilitation hospitals adjusting for age and baseline FIM score, and a longitudinal study of changes in mean FIM efficiency during a ten year period in one hospital, to examine the effects of different service organization and staff numbers.</p> <p>Results</p> <p>FIM efficiency (FIMEG) was inversely associated with age, and positively associated with admission FIM score. FIMEG was higher in the hospital with a coordinated care plan involving medical, nursing, occupational, physiotherapy staff and other healthcare providers working as a team, with a seamless interface with community rehabilitation services. Over a ten year period, reduction in staff numbers was associated with reduction in FIMEG, which may be offset to some extent by service re-engineering.</p> <p>Conclusion</p> <p>Within hospital organization of stroke rehabilitation services may influence outcome. A critical number of staff may be identified for the provision of services, below which rehabilitation efficiency may be affected.</p

Presenilin Controls CBP Levels in the Adult Drosophila Central Nervous System

Background: Dominant mutations in both human Presenilin (Psn) genes have been correlated with the formation of amyloid plaques and development of familial early-onset Alzheimer’s disease (AD). However, a definitive mechanism whereby plaque formation causes the pathology of familial and sporadic forms of AD has remained elusive. Recent discoveries of several substrates for Psn protease activity have sparked alternative hypotheses for the pathophysiology underlying AD. CBP (CREB-binding protein) is a haplo-insufficient transcriptional co-activator with histone acetly-transferase (HAT) activity that has been proposed to be a downstream target of Psn signaling. Individuals with altered CBP have cognitive deficits that have been linked to several neurological disorders. Methodology/Principal Findings: Using a transgenic RNA-interference strategy to selectively silence CBP, Psn, and Notch in adult Drosophila, we provide evidence for the first time that Psn is required for normal CBP levels and for maintaining specific global acetylations at lysine 8 of histone 4 (H4K8ac) in the central nervous system (CNS). In addition, flies conditionally compromised for the adult-expression of CBP display an altered geotaxis behavior that may reflect a neurological defect. Conclusions/Significance: Our data support a model in which Psn regulates CBP levels in the adult fly brain in a manner that is independent of Notch signaling. Although we do not understand the molecular mechanism underlying th

Predicting complete loss to follow-up after a health-education program: number of absences and face-to-face contact with a researcher

<p>Abstract</p> <p>Background</p> <p>Research on health-education programs requires longitudinal data. Loss to follow-up can lead to imprecision and bias, and <it>complete </it>loss to follow-up is particularly damaging. If that loss is predictable, then efforts to prevent it can be focused on those program participants who are at the highest risk. We identified predictors of complete loss to follow-up in a longitudinal cohort study.</p> <p>Methods</p> <p>Data were collected over 1 year in a study of adults with chronic illnesses who were in a program to learn self-management skills. Following baseline measurements, the program had one group-discussion session each week for six weeks. Follow-up questionnaires were sent 3, 6, and 12 months after the baseline measurement. A person was classified as completely lost to follow-up if none of those three follow-up questionnaires had been returned by two months after the last one was sent.</p> <p>We tested two hypotheses: that complete loss to follow-up was directly associated with the number of absences from the program sessions, and that it was less common among people who had had face-to-face contact with one of the researchers. We also tested predictors of data loss identified previously and examined associations with specific diagnoses.</p> <p>Using the unpaired t-test, the U test, Fisher's exact test, and logistic regression, we identified good predictors of complete loss to follow-up.</p> <p>Results</p> <p>The prevalence of complete loss to follow-up was 12.2% (50/409). Complete loss to follow-up was directly related to the number of absences (odds ratio; 95% confidence interval: 1.78; 1.49-2.12), and it was inversely related to age (0.97; 0.95-0.99). Complete loss to follow-up was less common among people who had met one of the researchers (0.51; 0.28-0.95) and among those with connective tissue disease (0.29; 0.09-0.98). For the multivariate logistic model the area under the ROC curve was 0.77.</p> <p>Conclusions</p> <p>Complete loss to follow-up after this health-education program can be predicted to some extent from data that are easy to collect (age, number of absences, and diagnosis). Also, face-to-face contact with a researcher deserves further study as a way of increasing participation in follow-up, and health-education programs should include it.</p

FE65 Binds Teashirt, Inhibiting Expression of the Primate-Specific Caspase-4

The Alzheimer disease (AD) amyloid protein precursor (APP) can bind the FE65 adaptor protein and this complex can regulate gene expression. We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex. We screened stable cell lines with a macroarray focusing on AD-related genes and identified CASP4, encoding caspase-4, as a target of this silencing complex. Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. Expression studies in postmortem samples demonstrated decreasing expression of Teashirt and increasing expression of caspase-4 with progressive cognitive decline. Importantly, there were significant increases in caspase-4 expression associated with even the earliest neuritic plaque changes in AD. We evaluated a case-control cohort and observed evidence for a genetic association between the Teashirt genes TSHZ1 and TSHZ3 and AD, with the TSHZ3 SNP genotype correlating with expression of Teashirt3. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD. Thus the cell biological, gene expression and genetic data support a role for Teashirt/caspase-4 in AD biology. As caspase-4 shows evidence of being a primate-specific gene, current models of AD and other neurodegenerative conditions may be incomplete because of the absence of this gene in the murine genome

Systemic therapy of Cushing’s syndrome

Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used in first-line in CD. CS patients are at an overall 4-fold higher mortality rate than age- and gender-matched subjects in the general population. The following article describes the most prominent substances used for clinical management of CS and gives a systematic overview of safety profiles, pharmacokinetic (PK)-parameters, and regulatory framework

New live screening of plant-nematode interactions in the rhizosphere

Abstract Free living nematodes (FLN) are microscopic worms found in all soils. While many FLN species are beneficial to crops, some species cause significant damage by feeding on roots and vectoring viruses. With the planned legislative removal of traditionally used chemical treatments, identification of new ways to manage FLN populations has become a high priority. For this, more powerful screening systems are required to rapidly assess threats to crops and identify treatments efficiently. Here, we have developed new live assays for testing nematode responses to treatment by combining transparent soil microcosms, a new light sheet imaging technique termed Biospeckle Selective Plane Illumination Microscopy (BSPIM) for fast nematode detection, and Confocal Laser Scanning Microscopy for high resolution imaging. We show that BSPIM increased signal to noise ratios by up to 60 fold and allowed the automatic detection of FLN in transparent soil samples of 1.5 mL. Growing plant root systems were rapidly scanned for nematode abundance and activity, and FLN feeding behaviour and responses to chemical compounds observed in soil-like conditions. This approach could be used for direct monitoring of FLN activity either to develop new compounds that target economically damaging herbivorous nematodes or ensuring that beneficial species are not negatively impacted

Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions