Daily low-dose prednisolone to prevent relapse of steroid-sensitive nephrotic syndrome in children with an upper respiratory tract infection:PREDNOS2 RCT

BACKGROUND: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5-7 days during an upper respiratory tract infection reduces the risk of relapse. OBJECTIVES: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. DESIGN: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. SETTING: A total of 122 UK paediatric departments, of which 91 recruited patients. PARTICIPANTS: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. RESULTS: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference -0.024, 95% confidence interval -0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. LIMITATIONS: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. CONCLUSIONS: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. FUTURE WORK: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information

Economic Evaluation of Interventions in Parkinson's Disease : A Systematic Literature Review

BackgroundParkinson's disease (PD) management comprises of drug treatments, surgery, and physical activity/occupational therapies to relieve PD's symptoms. The aim of this study is twofold; first, to appraise recent economic evaluation studies on PD management in order to update the existing knowledge; and second, to facilitate decision making on PD management by assessing the cost‐effectiveness of all types of PD interventions.MethodsA systematic search for studies published between 2010 and 2018 was conducted. The inclusion and exclusion of the articles were based on criteria relevant to population, intervention, comparison, outcomes, and study design (PICO). The reporting quality of the articles was assessed according to Consolidated Health Economic Evaluation Reporting Standards.ResultsTwenty‐eight articles were included, 10 of which were evaluations of drug treatments, 10 deep brain stimulation (DBS), and eight physical/occupational therapies. Among early‐stage treatments, Ti Ji dominated all physical activity interventions; however, its cost‐effectiveness should be further explored in relation to its duration, intensity, and frequency. Multidisciplinary interventions of joint medical and nonmedical therapies provided slightly better health outcomes for the same costs. In advanced PD patients, adjunct drug treatments could become more cost‐effective if introduced during early PD and, although DBS was more cost‐effective than adjunct drug therapies, the results were time‐bound.ConclusionsConditionally, certain PD interventions are cost‐effective. However, PD progression differs in each patient; thus, the cost‐effectiveness of individually tailored combinations of interventions that could provide more time in less severe disease states and improve patients’ and caregivers’ quality of life, should be further explored

Inland waterways and population health and wellbeing:a cross‐sectional study of waterway users in the UK

Natural environments, such as inland waterways (IWs), have been identified as a potential means to increase physical activity and promote health and wellbeing. However, further information on predictors of IW usage and their relationship with health and wellbeing outcomes is needed. Data were taken from the cross-sectional UK Waterways Engagement Monitor survey of waterway users (n = 21,537) in 2019/2020. Health outcome measures were life satisfaction, physical activity, and mental wellbeing. Visit frequency was an additional outcome measure. Both bivariate and multivariable associations between outcome measures and features of IWs were explored. The travel-cost method was used to estimate users’ demand, expressed by travel costs to waterways. Multivariable models showed positive associations of frequent visits and use for recreational/leisure purposes with life satisfaction and physical activity. Rural visits were associated with higher life satisfaction than urban ones. Lower visit satisfaction negatively impacted life satisfaction and mental wellbeing. Visit frequency was influenced by individual characteristics and purpose of visit, including visits for exercise. Waterway visits were inversely associated with travel costs (IRR = 0.99, p-value ≤ 0.001), and there was greater demand elasticity for short distances (≤5 miles). Socioeconomic-related inequalities were present. Future policies could enhance frequent use of waterways and alleviate accessibility-related inequalities to improve population health outcomes

Using economics to impact local obesity policy:introducing the UK Centre for Economics of Obesity (CEO)

Worldwide, population obesity levels are at their highest recorded levels, having nearly tripled between 1975 and 2016. This leads to substantial pressure on health systems, a negative impact on economic development, and results in adverse physical and mental health outcomes. There are many economic reasons why reducing population obesity should be a priority, and global targets have been set with many governments pledging to reduce obesity levels by 2030. To achieve these targets, a ‘system-wide’ approach has been widely advocated in direct recognition of the wide-ranging complex interacting determinants of the disease. This system approach requires action at all levels, including at the local government level, to use all fiscal and non-fiscal levers to bring about local system change that promotes healthier population behaviours. Like many country contexts, in England, local resources for achieving this system change have been drastically reduced in recent years. Economic evaluation offers a formal explicit framework to support local decision making but, to date, there has been a disconnect between national guidance on cost-effectiveness and how that informs local action. A new Centre for Economics of Obesity has been purposively developed to work closely with local government to adapt methods to help achieve efficiency and equity gains. By working across six workstreams to begin with, this Centre will use economics to inform policy action on different but interrelated parts of the obesity system and act as a training hub for health economists working in obesity policy

Economic evaluation of using daily prednisolone versus placebo at the time of an upper respiratory tract infection for the management of children with steroid-sensitive nephrotic syndrome:a model-based analysis

BACKGROUND: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. OBJECTIVE: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. METHODS: A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. RESULTS: The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. CONCLUSION: A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41669-022-00334-6

Evaluation of Daily Low-Dose Prednisolone during Upper Respiratory Tract Infection to Prevent Relapse in Children with Relapsing Steroid-Sensitive Nephrotic Syndrome:The PREDNOS 2 Randomized Clinical Trial

Importance: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. Objective: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. Interventions: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2daily or their alternate-day dose, whichever was greater. Main Outcomes and Measures: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. Results: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P =.70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P =.09). Conclusions and Relevance: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. Trial Registration: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.</p