The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

Background: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF. Methods: Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken. Results: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective. Conclusions: Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered

Prevalence of severe childhood obesity in England:2006-2013

BACKGROUND: International evidence shows that severe paediatric obesity results in an increased risk of ill health and may require specialised weight management strategies, yet there remains a lack of data on the extent of the problem. OBJECTIVE: To examine the prevalence of severe obesity in children aged 4-5 and 10-11 years, attending English schools between 2006/2007 and 2012/2013. DESIGN: A retrospective analysis of National Child Measurement Programme (NCMP) data. SETTING: Maintained schools in England. PARTICIPANTS: All children aged 4-5 and 10-11 years included in the NCMP dataset. MAIN OUTCOME MEASURES: Prevalence of severe childhood obesity, defined using the 99.6th centile of the British 1990 (UK90) growth reference for body mass index (BMI), analysed by sex, geography, ethnic group and deprivation. RESULTS: The key findings show that in 2012/2013, severe obesity (BMI ≥UK90 99.6th centile) was found in 1.9% of girls and 2.3% of boys aged 4-5 years, and 2.9% of girls and 3.9% of boys aged 10-11 years. Severe obesity prevalence varies geographically and is more prevalent in children from deprived areas, and among those from black ethnic groups. CONCLUSIONS: The findings from this study should help to raise awareness of the prevalence of severe obesity and support the provision of adequate treatment and prevention services both to support children who are already severely obese and reduce the prevalence of extreme weight in the future

Comparing new treatments for idiopathic pulmonary fibrosis - a network meta-analysis

BACKGROUND: The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison.METHODS: We searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation.RESULTS: Of 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone.CONCLUSIONS: Two treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.</p

The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF.METHODS: Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken.RESULTS: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective.CONCLUSIONS: Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered.</p

Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic - the risk of aerosol generation during medical procedures

With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI)?=?4.31 (0.83-22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams

Analysis of the air samples using the WHO (2007) AGP definitions and including chest physiotherapy.

a<p>Sample considered positive if aerosol <7.3 µm indicated the present of H1N1.</p>b<p>n unique patients refers to the number of patients these samples were taken from.</p><p>Column A: Results from univariable logistic regression models examining potential risk factors for production of H1N1 positive aerosol. Sample considered positive if aerosol <7.3 µm indicated the presence of H1N1. Estimates adjusted for repeated measurements.</p><p>Column B: Results from univariable negative binomial regression models examining potential risk factors for copy number per litre per minute given H1N1 positive aerosol.</p><p>A hyphen (-) indicates no positive samples in category. Referent refers to the category of an ordinal or nominal variable against which other categories are compared in the regression model and for which <i>no</i> dummy variable is included in the regression model.</p

Demographic and patient specific conditions of air samples.

a<p>Sample considered positive if aerosol <7.3 µm indicated the present of H1N1.</p>b<p>n unique patients refers to the number of patients these samples were taken from.</p><p>Column A: Results from univariable logistic regression models examining potential risk factors for production of H1N1 positive aerosol. Sample considered positive if aerosol <7.3 µm indicated the presence of H1N1. Estimates adjusted for repeated measurements.</p><p>Column B: Results from univariable negative binomial regression models examining potential risk factors for copy number per litre per minute given H1N1 positive aerosol.</p><p>A hyphen (-) indicates no positive samples in category. Referent refers to the category of an ordinal or nominal variable against which other categories are compared in the regression model and for which <i>no</i> dummy variable is included in the regression model.</p

The percentage of total RNA collected in each stage (size range) of the May impinger compared based on the WHO 2009 AGP definitions.

<p>The percentage of total RNA collected in each stage (size range) of the May impinger compared based on the WHO 2009 AGP definitions.</p