Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Cost-Effectiveness Analysis of Natriuretic Peptide Testing and Specialist Management in Patients with Suspected Acute Heart Failure

Objectives: To determine the cost-effectiveness of natriuretic peptide (NP) testing and specialist outreach in patients with acute heart failure (AHF) residing off the cardiology ward. Methods: We used a Markov model to estimate costs and quality-adjusted life-years (QALYs) for patients presenting to hospital with suspected AHF. We examined diagnostic workup with and without the NP test in suspected new cases, and we examined the impact of specialist heart failure outreach in all suspected cases. Inputs for the model were derived from systematic reviews, the UK national heart failure audit, randomized controlled trials, expert consensus from a National Institute for Health and Care Excellence guideline development group, and a national online survey. The main benefit from specialist care (cardiology ward and specialist outreach) was the increased likelihood of discharge on disease-modifying drugs for people with left ventricular systolic dysfunction, which improve mortality and reduce re-admissions due to worsened heart failure (associated with lower utility). Costs included diagnostic investigations, admissions, pharmacological therapy, and follow-up heart failure care. Results: NP testing and specialist outreach are both higher cost, higher QALY, cost-effective strategies (incremental cost-effectiveness ratios of £11,656 and £2,883 per QALY gained, respectively). Combining NP and specialist outreach is the most cost-effective strategy. This result was robust to both univariate deterministic and probabilistic sensitivity analyses. Conclusions: NP testing for the diagnostic workup of new suspected AHF is cost-effective. The use of specialist heart failure outreach for inpatients with AHF residing off the cardiology ward is cost-effective. Both interventions will help improve outcomes for this high-risk group

Remote preconditioning in normal and hypertrophic rat hearts

<p>Abstract</p> <p>Background</p> <p>The aim of our study was to investigate whether remote preconditioning (RPC) improves myocardial function after ischemia/reperfusion injury in both normal and hypertrophic isolated rat hearts. This is the first time in world literature that cardioprotection by RPC in hypertrophic myocardium is investigated.</p> <p>Methods</p> <p>Four groups of 7 male Wistar rats each, were used: Normal control, normal preconditioned, hypertrophic control and hypertrophic preconditioned groups. Moderate cardiac hypertrophy was induced by fludrocortisone acetate and salt administration for 30 days. Remote preconditioning of the rat heart was achieved by 20 minutes transient right hind limb ischemia and 10 minutes reperfusion of the anaesthetized animal. Isolated Langendorff-perfused animal hearts were then subjected to 30 minutes of global ischemia and reperfusion for 60 minutes. Contractile function and heart rhythm were monitored. Preconditioned groups were compared to control groups.</p> <p>Results</p> <p>Left ventricular developed pressure (LVDP) and the product LVDP × heart rate (HR) were significantly higher in the hypertrophic preconditioned group than the hypertrophic control group while left ventricular end diastolic pressure (LVEDP) and severe arrhythmia episodes did not differ. Variances between the normal heart groups were not significantly different except for the values of the LVEDP in the beginning of reperfusion.</p> <p>Conclusions</p> <p>Remote preconditioning seems to protect myocardial contractile function in hypertrophic myocardium, while it has no beneficial effect in normal myocardium.</p

Mutation in the Gene Encoding Ubiquitin Ligase LRSAM1 in Patients with Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth disease (CMT) represents a family of related sensorimotor neuropathies. We studied a large family from a rural eastern Canadian community, with multiple individuals suffering from a condition clinically most similar to autosomal recessive axonal CMT, or AR-CMT2. Homozygosity mapping with high-density SNP genotyping of six affected individuals from the family excluded 23 known genes for various subtypes of CMT and instead identified a single homozygous region on chromosome 9, at 122,423,730–129,841,977 Mbp, shared identical by state in all six affected individuals. A homozygous pathogenic variant was identified in the gene encoding leucine rich repeat and sterile alpha motif 1 (LRSAM1) by direct DNA sequencing of genes within the region in affected DNA samples. The single nucleotide change mutates an intronic consensus acceptor splicing site from AG to AA. Direct analysis of RNA from patient blood demonstrated aberrant splicing of the affected exon, causing an obligatory frameshift and premature truncation of the protein. Western blotting of immortalized cells from a homozygous patient showed complete absence of detectable protein, consistent with the splice site defect. LRSAM1 plays a role in membrane vesicle fusion during viral maturation and for proper adhesion of neuronal cells in culture. Other ubiquitin ligases play documented roles in neurodegenerative diseases. LRSAM1 is a strong candidate for the causal gene for the genetic disorder in our kindred

Defining left ventricular remodeling following acute ST-segment elevation myocardial infarction using cardiovascular magnetic resonance.

The assessment of post-myocardial infarction (MI) left ventricular (LV) remodeling by cardiovascular magnetic resonance (CMR) currently uses criteria defined by echocardiography. Our aim was to provide CMR criteria for assessing LV remodeling following acute MI.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Cost-effectiveness of collaborative care for chronically ill patients with comorbid depressive disorder in the general hospital setting, a randomised controlled trial

Background. Depressive disorder is one of the most common disorders, and is highly prevalent in chronically ill patients. The presence of comorbid depression has a negative influence on quality of life, health care costs, self-care, morbidity, and mortality. Early diagnosis and well-organized treatment of depression has a positive influence on these aspects. Earlier research in the USA has reported good results with regard to the treatment of depression with a collaborative care approach and an antidepressant algorithm. In the UK 'Problem Solving Treatment' has proved to be feasible. However, in the general hospital setting this approach has not yet been evaluated. Methods/Design. CC: DIM (Collaborative Care: Depression Initiative in the Medical setting) is a two-armed randomised controlled trial with randomisation at patient level. The aim of the trial is to evaluate the treatment of depressive disorder in general hospitals in the Netherlands based on a collaborative care framework, including contracting, 'Problem Solving Treatment', antidepressant algorithm, and manual-guided self-help. 126 outpatients with diabetes mellitus, chronic obstructive pulmonary disease, or cardiovascular diseases will be randomised to either the intervention group or the control group. Patients will be included if they have been diagnosed with moderate to severe depression, based on the DSM-IV criteria in a two-step screening method. The intervention group will receive treatment based on the collaborative care approach; the control group will receive 'care as usual'. Baseline and follow-up measurements (after 3, 6, 9, and 12 months) will be performed by means of questionnaires. The primary outcome measure is severity of depressive symptoms, as measured with the PHQ-9. The secondary outcome measure is the cost-effectiveness of these treatments according to the TiC-P, the EuroQol and the SF-36. Discussion. Earlier research has indicated that depressive disorder is a chronic, mostly recurrent illness, which tends to cluster with physical comorbidity. Even though the treatment of depressive disorder based on the guidelines for depression is proven effective, these guidelines are often insufficiently adhered to. Collaborative care and 'Problem Solving Treatment' will be specifically tailored to patients with depressive disorders and evaluated in a general hospital setting in the Netherlands

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research

Effectiveness of a self-management training for patients with chronic and treatment resistant anxiety or depressive disorders on quality of life, symptoms, and empowerment : results of a randomized controlled trial

Background: Anxiety and depressive disorders are common mental disorders. A substantial part of patients does not achieve symptomatic remission after treatment in specialized services. Current care as usual (CAU) for these patients consists of long-term supportive contacts. Termination of CAU is often not considered to be an option due to persistent symptoms, a low level of functioning, and the absence of further treatment options. A new intervention, ZemCAD, offers a program focused on rehabilitation and self-management, followed by referral back to primary care. Methods: This multicenter randomized controlled trial was carried out in twelve specialized outpatient mental health care services in the Netherlands. Consenting and eligible patients were invited for the MINI interview and the baseline questionnaire. Assessments were done at 6 (T1), 12 (T2) and 18 (T3) months post baseline. We used linear mixed model analysis (LMM) to ascertain the effectiveness of the ZemCAD group relative to the CAU group on quality of life, symptom severity and empowerment. Results: In total 141 patients were included. The results at 18-month follow-up regarding to quality of life and symptom severity, showed no significant differences between the ZemCAD group and the CAU group, except on the 'social relationships'-domain (d = 0.37). With regard to empowerment a significant difference between both groups was observed in the total empowerment score and one empowerment dimension (d = 0.45 and d = 0.39, respectively). After the ZemCAD intervention, more patients went from specialized outpatient mental health services back to a less specialized health care setting with less intensive treatment, such as primary care. Conclusion: The findings in this study suggest that patients with chronic and treatment-resistant anxiety and depression using the ZemCAD intervention improve on empowerment but not on symptom severity or quality of life. Since little is known about the effects of rehabilitation and self-management in patients with chronic and treatment resistant anxiety and depressive disorders, this is a first attempt to provide a proof-of-concept study in this under-researched but important field. Trial registration: Netherlands Trial Register: NTR3335, registered 7 March 2012

Ischaemic conditioning and reperfusion injury

The 30-year anniversary of the discovery of 'ischaemic preconditioning' is in 2016. This endogenous phenomenon can paradoxically protect the heart from acute myocardial infarction by subjecting it to one or more brief cycles of ischaemia and reperfusion. Apart from complete reperfusion, this method is the most powerful intervention known for reducing infarct size. The concept of ischaemic preconditioning has evolved into 'ischaemic conditioning', a term that encompasses a number of related endogenous cardioprotective strategies, applied either directly to the heart (ischaemic preconditioning or postconditioning) or from afar, for example a limb (remote ischaemic preconditioning, perconditioning, or postconditioning). Investigations of signalling pathways underlying ischaemic conditioning have identified a number of therapeutic targets for pharmacological manipulation. Over the past 3 decades, a number of ischaemic and pharmacological cardioprotection strategies, discovered in experimental studies, have been examined in the clinical setting of acute myocardial infarction and CABG surgery. The results from many of the studies have been disappointing, and no effective cardioprotective therapy is currently used in clinical practice. Several large, multicentre, randomized, controlled clinical trials on cardioprotection have highlighted the challenges of translating ischaemic conditioning and pharmacological cardioprotection strategies into patient benefit. However, a number of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischaemic heart disease