International Standards For Commercial Mediators

This paper talks about the international standards for commercial mediators. It introduces the standards of eight different jurisdictions and afterwards, evaluates whether there should be one accrediting standard for all international commercial mediators. In the introduction chapter, the paper talks about the problems with the current legal system and then explains the growth of mediation in today’s society. By discussing the nature and practice of mediation, whether mediation should be compulsory or voluntary in light of Article 6 of the European Convention on Human Rights, rationale of the various jurisdictions covered, the paper then talks about the attributes that make a good mediator as well as the accreditation and training of mediators. From chapter two to chapter nine, the paper focuses on eight jurisdictions in which mediation is firmly enshrined within one legal culture to those that are just embarking on the concept (namely Australia, New Zealand, Indonesia, Malaysia, India, Hong Kong, California and Canada). Each chapter talks about the developments of commercial mediation, law and institutions as well as training and accreditation of mediators within their respective jurisdictions. In the concluding chapter, it discusses whether there should be one accrediting standard for international commercial mediators by exploring the advantages and disadvantages of having one accrediting standard as well as the author’s analysis and point of view on the subject

Searching and ranking ontologies on the Semantic Web

The number of ontologies available online is increasing constantly. Tools that are capable of searching, retrieving, and ranking ontologies are becoming crucial to facilitate ontology search and reuse. In this document, we describe OntoSearch, which is a tool for capturing and searching ontologies on the Semantic web. We also briefly describe AKTiveRank which is used to rank OWL ontologies based on certain ontology-structure analysis.

Meta-Analysis of Adipose Tissue Derived Cell-Based Therapy for the Treatment of Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative disorder associated with cartilage loss and is a leading cause of disability around the world. In old age, the capacity of cartilage to regenerate is diminished. With an aging population, the burden of OA is set to rise. Currently, there is no definitive treatment for OA. However, cell-based therapies derived from adipose tissue are promising. A PRISMA systematic review was conducted employing four databases (MEDLINE, EMBASE, Cochrane, Web of Science) to identify all clinical studies that utilized adipose tissue derived mesenchymal stem cells (AMSCs) or stromal vascular fraction (SVF) for the treatment of knee OA. Eighteen studies were included, which met the inclusion criteria. Meta-analyses were conducted on fourteen of these studies, which all documented WOMAC scores after the administration of AMSCs. Pooled analysis revealed that cell-based treatments definitively improve WOMAC scores, post treatment. These improvements increased with time. The studies in this meta-analysis have established the safety and efficacy of both AMSC therapy and SVF therapy for knee OA in old adults and show that they reduce pain and improve knee function in symptomatic knee OA suggesting that they may be effective therapies to improve mobility in an aging population

Synovium-Derived Mesenchymal Stem Cell Transplantation in Cartilage Regeneration: A PRISMA Review of in vivo Studies.

Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage in vitro and in vivo. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential. We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in in vivo studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Twenty studies were included in our review; four examined the use of human sMSCs and 16 were conducted using sMSCs harvested from animals. Most studies reported successful cartilage repair with sMSC transplantation despite the variability of animals, cell harvesting techniques, methods of delivery, and outcome measures. We conclude that sMSC transplantation holds promise as a treatment option for focal cartilage defects. We believe that defining the cell population being used, establishing standardized methods for MSC delivery, and the use of objective outcome measures should enable future high quality studies such as randomized controlled clinical trials to provide the evidence needed to manage chondral lesions optimally

Infrapatellar fat pad adipose-derived stem cells co-cultured with articular chondrocytes from osteoarthritis patients exhibit increased chondrogenic gene expression.

AIM: The variable results in clinical trials of adipose tissue-derived stem cells (ASCs) for chondral defects may be due to the different ex vivo culture conditions of the ASCs which are implanted to treat the lesions. We sought to determine the optimal in vitro chondrocyte co-culture condition that promotes infrapatellar fat pad-derived (IFPD) ASC chondrogenic gene expression in a novel co-culture combination. METHODS: In our study, we utilized an in vitro autologous co-culture of IFPD ASCs and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic human knee joints at ASC-to-chondrocyte seeding log ratios of 1:1, 10:1, and 100:1. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenic gene expression. RESULTS: The chondrogenic gene expression profiles from co-cultures were greater than would be expected from an expression profile modeled from chondrocyte and ASC-only monocultures. Additionally, chondrogenic gene expression decreased with increasing ASC-to-chondrocyte seeding ratios. CONCLUSIONS: These findings provide insight into the mechanisms underlying clinical ASC therapies and signifies that IFPD ASCs pre-conditioned by chondrocyte co-culture may have improved chondrogenic potential for cartilage repair. This model can help further understand IFPD ASCs in chondral and osteochondral repair and the chondrogenic pathways involved. Video Abstract

An international initiative to create a collaborative for pharmacovigilance in hospice and palliative care clinical practice

Background: Medication registration currently requires evidence of safety and efficacy from adequately powered phase 3 studies. Pharmacovigilance (phase 4 studies, postmarketing data, adverse drug reaction reporting) provide data on more widespread and longer term use. Historically, voluntary reporting systems for pharmacovigilance have had low reporting rates, relying on ad hoc reporting and retrospective chart reviews, or prospective registries have often been limited to specific drugs or clinical conditions. Furthermore, these data are often irrelevant in hospice and palliative care due to the timeliness of which such data become available and the unique characteristics of our population and prescribing: compounding comorbidities, progressive organ failure, accumulation of symptom-specific medications, tendency to attribute toxicity to disease progression, use of old, off-patent medications, and incorporation of evolving evidence. There is a need for prospective, systematic pharmacovigilance in hospice and palliative care. Method: Here we describe an international, Web-based, 128-bit secure initiative to collect pharmacovigilance data documenting net clinical benefit and safety of common medications. The intention is for a diverse and large group of clinical units to record data prospectively on a small deidentified consecutive cohort of patients started on the medication of interest. A new medication would be studied every 3 months. Three key time points (different for each medication) will be assessed for each patient, collecting easily codefiable data at baseline, a point at which clinical benefit should be experienced, and a point at which short- to medium-term toxicities may occur. Toxicities can additionally be recorded at any time they occur. Data collection will take a maximum of 10 minutes per patient. Conclusion: The intention is to create an efficient, relevant system to improve hospice and palliative care with maximally generalizable results

The role of ondansetron in the management of cholestatic or uremic pruritis - a systematic review

Pruritus associated with hepatic or renal failure can be a troublesome symptom, refractory to treatment, associated with significant physical and emotional distress, and reduction in quality of life for patients already burdened with chronic disease. Serotonin has been implicated as a possible pathological mediator, and therefore 5HT3 antagonists have been suggested as a possible therapeutic intervention. Objectives This review of the literature systematically explores the role of ondansetron in the management of cholestatic or uraemic pruritus. Methods Electronic databases were systematically searched for randomized controlled trials (RCTs) examining the role of ondansetron in cholestatic or uraemic pruritus between 1966 and 2008. Results Five RCTs were included in this systematic review: three for cholestatic pruritus, and two for uraemic pruritus. All trials examined ondansetron versus placebo, however with differing treatment protocols. Overall, three studies showed no benefit to ondansetron over placebo, however two studies in cholestatic pruritus showed small reductions in pruritus with questionable clinical significance. Conclusion Ondansetron was demonstrated to have negligible effect on cholestatic or uraemic pruritus on the basis of a limited number of studies

Anti-cholinergic load, health care utilization, and survival in people with advanced cancer: a pilot study

Introduction: Anti-cholinergic medications have been associated with increased risks of cognitive impairment, premature mortality and increased risk of hospitalisation. Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer, yet little is known about associated adverse outcomes in this setting. Methods: A substudy of 112 participants in a randomised control trial who had cancer and an Australia modified Karnofsky Performance Scale (AKPS) score (AKPS) of 60 or above, explored survival and health service utilisation; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale (modified version) longitudinally to death. A standardised starting point for prospectively calculating survival was an AKPS of 60 or above. Results: Baseline entry to the sub-study was a mean 62 ± 81 days (median 37, range 1–588) days before death (survival), with mean of 4.8 (median 3, SD 4.18, range 1 – 24) study assessments in this time period. Participants spent 22% of time as an inpatient. There was no significant association between anti-cholinergic score and time spent as an inpatient (adjusted for survival time) (p = 0.94); or survival time. Discussion: No association between anti-cholinergic load and survival or time spent as an inpatient was seen. Future studies need to include cognitively impaired populations where the risks of symptomatic deterioration may be more substantial