Rhabdomyolysis reported for children and adolescents treated with antipsychotic medicines: a case series analysis

published_or_final_versio

Rhabdomyolysis reported for children and adolescents treated with antipsychotic medicines: a case series analysis

published_or_final_versio

Cost-Effectiveness Findings from the Agewell Pilot Study of Behaviour Change to Promote Health and Wellbeing in Later Life.

Background: Participation in cognitive and physical activities may help to maintain health and wellbeing in older people. The Agewell study explored the feasibility of increasing cognitive and physical activity in older people through a goal-setting approach. This paper describes the findings of the cost-effectiveness analysis. Method: Individuals over the age of 50 and attending an Agewell centre in North Wales were randomised to one of three conditions: control (IC), goal-setting (GS), or goal-setting with mentoring (GM). We undertook a cost-effectiveness analysis comparing GS vs. IC, GM vs. IC and GM vs. GS. The primary outcome measure for this analysis was the QALY, calculated using the EQ-5D. Participants’ health and social care contacts were recorded and costed using national unit costs. Results: Seventy participants were followed-up at 12 months. Intervention set up and delivery costs were £252 per participant in the GS arm and £269 per participant in the GM arm. Mean health and social care costs over 12 months were £1,240 (s.d. £3,496) per participant in the IC arm, £1,259 (s.d. £3,826) per participant in the GS arm and £1,164 (s.d. £2,312) per participant in the GM arm. At a willingness to pay threshold of £20,000 per QALY there was a 65% probability that GS was cost-effective compared to IC (ICER of £1,070). However, there was only a 41% probability that GM was cost-effective compared to IC (ICER of £2,830) at a threshold of £20,000 per QALY. Conclusion: Setting up and running the community based intervention was feasible. Due to the small sample size it is not possible to draw a firm conclusion about cost-effectiveness; however, our preliminary results suggest that goal- setting is likely to be cost-effective compared to the control condition of no goal-setting, the addition of mentoring was effective but not cost-effective.Lifelong Health and Well-being Programme through the Medical Research Counci

The Agewell trial: a pilot randomised controlled trial of a behaviour change intervention to promote healthy ageing and reduce risk of dementia in later life.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk. We evaluated a goal-setting intervention aimed at promoting increased cognitive and physical activity and improving mental and physical fitness, diet and health. METHODS: This was a pilot randomised controlled trial designed to guide planning for a larger-scale investigation, provide preliminary evidence regarding efficacy, and explore feasibility and acceptability. Primary outcomes were engagement in physical and cognitive activity. Participants aged over 50 living independently in the community were recruited through a community Agewell Centre. Following baseline assessment participants were randomly allocated to one of three conditions: control (IC) had an interview in which information about activities and health was discussed; goal-setting (GS n = 24) had an interview in which they set behaviour change goals relating to physical, cognitive and social activity, health and nutrition; and goal-setting with mentoring (GM, n = 24) had the goal-setting interview followed by bi-monthly telephone mentoring. Participants and researchers were blinded to group assignment. Participants were reassessed after 12 months. RESULTS: Seventy-five participants were randomised (IC n = 27, GS n = 24, GM n = 24). At 12-month follow-up, the two goal-setting groups, taken together (GS n = 21, GM n = 22), increased their level of physical (effect size 0.37) and cognitive (effect size 0.15) activity relative to controls (IC n = 27). In secondary outcomes, the two goal-setting groups taken together achieved additional benefits compared to control (effect sizes ≥ 0.2) in memory, executive function, cholesterol level, aerobic capacity, flexibility, balance, grip strength, and agility. Adding follow-up mentoring produced further benefits compared to goal-setting alone (effect sizes ≥ 0.2) in physical activity, body composition, global cognition and memory, but not in other domains. Implementation of the recruitment procedure, assessment and intervention was found to be feasible and the approach taken was acceptable to participants, with no adverse effects. CONCLUSIONS: A brief, low-cost goal-setting intervention is feasible and acceptable, and has the potential to achieve increased activity engagement. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30080637.This trial was funded by Medical Research Council grant G1001888/1 to LC, JVH, IRJ, JT and CJW. The funding body played no role in the design of the study, in collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We acknowledge the support of Age Cymru Gwynedd a Môn including John Clifford Jones, Maldwyn Roberts, Stephen Williams and Mici Plwm. We would like to thank Sharman Harris and Catrin Searell, Department of Clinical Chemistry, Ysbyty Gwynedd, Bangor, the volunteers at the Nefyn Agewell Centre, and all the members of the Nefyn Agewell Centre, and especially all those who took part in the research project. We are grateful to Professor Carol Brayne, Cambridge University, Professor Martin Knapp, London School of Economics, Professor Mike Martin, Zürich University, and Professor Robin Morris, King’s College London Institute of Psychiatry, who acted as external advisors to the project. Special thanks go to Andrew Brand for statistical advice

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

Trial protocol OPPTIMUM : does progesterone prophylaxis for the prevention of preterm labour improve outcome?

Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

The added value of ordinal analysis in clinical trials: an example in traumatic brain injury

INTRODUCTION: In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial. METHODS: We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics. RESULTS: Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively. CONCLUSIONS: Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects

Inhaled tobramycin solution-associated recurrent eosinophilia and severe persistent bronchospasm in a patient with cystic fibrosis: a case report

BACKGROUND: Delivery of tobramycin by inhalation to the lungs of patients with cystic fibrosis (CF) who are infected with Pseudomonas aeruginosa has been proven to be effective and safe. The aerosol administration allows high concentrations of tobramycin to be delivered to the site of infection with limited systemic absorption. In rare patients, systemic absorption of inhaled tobramycin may be significant enough to produce toxic effects, such as renal and vestibular toxicities. CASE PRESENTATION: We report a patient with CF who developed recurrent eosinophilia and severe persistent bronchospasm following repeated administration of preservative-free tobramycin by inhalation, beginning at 16 months of age. Also, he developed similar signs and symptoms when he was administered tobramycin intravenously on one occasion at 5 1/2 years. The patient had a history of environmental allergies. Temporal sequence of his signs and symptoms after each administration of tobramycin (similar to re-challenge testing), and his improvement after discontinuation of the drug strongly suggest an adverse drug reaction. CONCLUSION: Hypersensitivity reaction should be considered in patients who develop recurrent eosinophilia and deterioration of pulmonary function following the use of tobramycin by inhalation or by intravenous administration