Summary Background Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in ...osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT. Methods In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov , NCT00396279. Findings Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70–95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3–5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related. Interpretation Further investigation of denosumab as a therapy for GCT is warranted. Funding Amgen, Inc.
Adjuvant aromatase inhibitor therapy is well established in postmenopausal women with hormone receptor-positive breast cancer, but such therapy is complicated by accelerated bone loss and increased ...fracture risk. We investigated the ability of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, to protect against aromatase inhibitor-induced bone loss.
Eligible women with hormone receptor-positive nonmetastatic breast cancer treated with adjuvant aromatase inhibitor therapy were stratified by duration of aromatase inhibitor therapy (< or = 6 v > 6 months), received supplemental calcium and vitamin D, and were randomly assigned to receive placebo (n = 125) or subcutaneous denosumab 60 mg (n = 127) every 6 months. At enrollment, all patients were required to have evidence of low bone mass, excluding osteoporosis. The primary end point was percentage change from baseline at month 12 in lumbar spine bone mineral density (BMD).
At 12 and 24 months, lumbar spine BMD increased by 5.5% and 7.6%, respectively, in the denosumab group versus placebo (P < .0001 at both time points). Increases were observed as early as 1 month and were not influenced by duration of aromatase inhibitor therapy. Increases in BMD were also observed at the total hip, total body, femoral neck, and the predominantly cortical one-third radius. Bone turnover markers decreased with denosumab treatment. Overall incidence of treatment-emergent adverse events (AEs) was similar between treatment groups.
In women with nonmetastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy, twice-yearly administration of denosumab led to significant increases in BMD over 24 months at trabecular and cortical bone, with overall AE rates similar to those of placebo.
To assess the effects of consumer engagement in health care policy, research and services. We updated a review published in 2006 and 2009 and revised the previous search strategies for key databases ...(The Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; PsycINFO; CINAHL; Web of Science) up to February 2020. Selection criteria included randomised controlled trials assessing consumer engagement in developing health care policy, research, or health services. The International Association for Public Participation, Spectrum of Public Participation was used to identify, describe, compare and analyse consumer engagement. Outcome measures were effects on people; effects on the policy/research/health care services; or process outcomes. We included 23 randomised controlled trials with a moderate or high risk of bias, involving 136,265 participants. Most consumer engagement strategies adopted a consultative approach during the development phase of interventions, targeted to health services. Based on four large cluster-randomised controlled trials, there is evidence that consumer engagement in the development and delivery of health services to enhance the care of pregnant women results in a reduction in neonatal, but not maternal, mortality. From other trials, there is evidence that involving consumers in developing patient information material results in material that is more relevant, readable and understandable for patients, and can improve knowledge. Mixed effects are reported of consumer-engagement on the development and/or implementation of health professional training. There is some evidence that using consumer interviewers instead of staff in satisfaction surveys can have a small influence on the results. There is some evidence that consumers may have a role in identifying a broader range of health care priorities that are complementary to those from professionals. There is some evidence that consumer engagement in monitoring and evaluating health services may impact perceptions of patient safety or quality of life. There is growing evidence from randomised controlled trials of the effects of consumer engagement on the relevance and positive outcomes of health policy, research and services. Health care consumers, providers, researchers and funders should continue to employ evidence-informed consumer engagement in their jurisdictions, with embedded evaluation. Systematic review registration: PROSPERO CRD42018102595.
Posttraumatic stress disorder is common among military Veterans. While effective treatments exist, many Veterans either do not engage in treatment or fail to achieve full remission. Thus, there is a ...need to develop adjunctive complementary interventions to enhance treatment engagement and/or response. Equine-assisted activities and therapies (EAAT) are one category of animal assisted interventions that might serve this function. The aim of this article is to review the current state and challenges regarding the use of EAAT for Veterans with PTSD and provide a roadmap to move the field forward. EAAT hold promise as adjunctive complementary interventions for symptom reduction among Veterans with PTSD. Additionally, there is evidence that these approaches may enhance wellbeing in this population. At this time, many gaps in the literature exist and rigorous randomized controlled trials are needed before definitive conclusions can be drawn. The authors of this work provide recommendations as a roadmap to move the field forward. These include standardizing the EAAT nomenclature, focusing mechanism of action studies on the human-horse bond using biological metrics and using a standardized intervention model across studies.
Pilot assessment of an equine-assisted services intervention for Veterans with posttraumatic stress disorder.
Prospective cohort.
A large Veterans Administration healthcare system.
Two sessions of ...instruction in horsemanship skills and two sessions of trail rides.
Safety and feasibility of recruitment, retention, providing the intervention, and measuring outcomes, as well as acceptability of the intervention to the population studied were the main outcome measures.
There were no injuries among the 18 participants, 6 staff, or 11 equines over the 3 months of the study. Eleven of 12 (92 %) planned intervention sessions were provided, with one being canceled due to weather. Out of approximately 1800 potential subjects, 21 were enrolled within three months and three dropped out before the first session. The mean number of sessions attended was 3 % and 52 % of participants completed all sessions. The mean PACES score for all sessions together was 109 (SD = 12), with a range of 50–126. Pre- to one-month post-intervention exploratory results indicated increased psychological flexibility (p = 0.008) and positive affect (p = 0.008) as measured by the Acceptance and Action Questionnaire II and the Positive and Negative Affect Scale, respectively as well as decreased PTSD (p = 0.001) and depressive symptoms (p = 0.017) as measured by the PTSD Checklist for DSM 5 and the Beck Depression Inventory, respectively.
Results suggest the intervention can be conducted with minimal risk. Further, it was feasible to recruit participants as well as provide the intervention and measure exploratory outcomes. Session attendance and PACES scores indicate acceptability to the Veteran population. The exploratory results will provide sample size estimates for future randomized controlled studies of this intervention Future studies should plan for missed sessions due to weather and consider compensating subjects to enhance retention. Finally, this work provides preliminary evidence that this intervention, without a mental health treatment component, might benefit the mental health of Veterans with PTSD.
•Equine-assisted services have the potential to benefit Veterans with PTSD.•A horsemanship skills program was feasible to implement for this population.•Participation was associated with PTSD and mood symptom improvement.•Participation was also associated with enhanced psychological flexibility.
Sternal wound infections (SWIs) can be a devastating long-term complication with significant morbidity and health care cost. The purpose of this analysis was to evaluate the cost-effectiveness of ...negative pressure incision management systems (NPIMS) in cardiac surgery.
All cardiac surgery cases at an academic hospital with risk scores available (2009-2017) were extracted from an institutional database (n = 4455). Patients were stratified by utilization of NPIMS, and high risk was defined as above the median. Costs included infection-related readmissions and were adjusted for inflation. Multivariable regression models assessed the risk-adjusted cost of SWI and efficacy of NPIMS use. Cost-effectiveness was modeled using TreeAge Pro using institutional results.
The rate of deep SWI was 0.9% with an estimated cost of $111,175 (P < 0.0001). The rate of superficial SWI was 0.8% at a cost of $7981 (P = 0.08). Risk-adjusted NPIMS use was not significantly associated with reduced SWI (OR 1.2, P = 0.62) and thus not cost-effective. However, in the high-risk cohort with an OR 0.84 (P = 0.72) and SWI rate of 2.3%, NPIMS use cost $205 per patient with an incremental cost-effectiveness ratio of $179,092. Therefore, NPIMS is estimated to be cost-effective with a deep SWI rate over 1.3% or improved efficacy (OR < 0.83).
SWIs are extremely expensive complications with estimates of $111,175 for deep yet only $7981 for superficial. Although NPIMS was not cost-effective for SWI prevention as currently utilized, a protocol for use on patients with a higher risk of sternal infection could be cost-effective.
Human-animal bond is defined as the mutually beneficial relationship between humans and animals. Recent years have seen increasing research regarding the benefits of interaction with animals for ...autistic children. However, there continue to be limited studies exploring the impact of this interaction on the welfare of therapy dogs. As part of a pilot randomised control trial assessing the efficacy of canine-assisted occupational therapy with autistic children, this project assessed welfare markers of the therapy dog involved. A total of twenty-one saliva samples were taken from the therapy dog to assess cortisol, alpha amylase, and oxytocin concentrations at home and throughout the treatment days. Additionally, six hours of therapy session videos were analysed for stress indicators of canine behaviour. No significant differences were found between days spent at home and treatment days for any of the biomarkers or stress indicators. Results suggest that the therapy dog involved did not experience increased stress resulting from interaction with the autistic children throughout the therapy sessions. This study supports the need for further research regarding therapy dog welfare when interacting with autistic children including an increased sample size of therapy dogs and therapists.
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