Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Background: Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), etanercept (Enbrel®, Pfizer, New York, NY, USA) and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. Objective: To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Data sources: Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Review methods: Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Results: Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks’ follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE’s usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted. Limitations: The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children. Conclusions: The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities. Study registration: This study is registered as PROSPERO CRD42016039494. Funding: The National Institute for Health Research Health Technology Assessment programme

Audit of therapeutic interventions in inpatient children using two scores: are they evidence-based in developing countries?

BACKGROUND: The evidence base of clinical interventions in paediatric hospitals of developing countries has not been formally assessed. We performed this study to determine the proportion of evidence-based therapeutic interventions in a paediatric referral hospital of a developing country METHODS: The medical records of 167 patients admitted in one-month period were revised. Primary diagnosis and primary therapeutic interventions were determined for each patient. A systematic search was performed to assess the level of evidence for each intervention. Therapeutic interventions were classified using the Ellis score and the Oxford Centre for Evidence Based Medicine Levels of Evidence RESULTS: Any dehydration due to diarrhoea (59 cases) and pneumonia (42 cases) were the most frequent diagnoses. Based on Ellis score, level I evidence supported the primary therapeutic intervention in 21%, level II in 73% and level III in 6% cases. Using the Oxford classification 16%, 8%, 1% and 75% therapeutic interventions corresponded to grades A, B, C, and D recommendations, respectively. Overall, according to Ellis score, 94% interventions were evidence based. However, out of the total, 75% interventions were based on expert opinion or basic sciences. Most children with mild to moderate dehydration (52 cases) were inappropriately treated with slow intravenous fluids, and most children with non-complicated community acquired pneumonia (42 cases) received intravenous antibiotics CONCLUSIONS: Most interventions were inappropriate, despite the availability of effective therapy for several of them. Diarrhoeal dehydration and community acquired pneumonia were the most common diagnoses and were inappropriately managed. Existing effective interventions for dehydration and pneumonia need to be put into practice at referral hospitals of developing countries. For the remaining problems, there is the need to conduct appropriate clinical studies. Caution must be taken when assigning the level of evidence supporting therapeutic interventions, as commonly used classifications may be misleadin

Swedish Parents’ Experiences of Parenthood and the Need for Support to Siblings When a Baby is Stillborn

Background:It has been argued that having a stillborn baby in the family affects older siblings more than parents realize. The aim of this study was to describe parenthood and the needs of siblings after stillbirth from the parents' perspective.Methods:Six focus groups were held with 27 parents who had experienced a stillbirth and who had had children before the loss. The discussion concerned parents' support to the siblings, and the sibling's meeting, farewell, and memories of their little sister or brother. Data were analyzed using qualitative content analysis.Results:The overall theme of the findings was parenthood in a balance between grief and everyday life. In the analysis, three categories emerged that described the construction of the theme: support in an acute situation, sharing the experiences within the family, and adjusting to the situation.Conclusions:The siblings' situation is characterized by having a parent who tries to maintain a balance between grief and everyday life. Parents are present and engaged in joint activities around the stillbirth together with the siblings of the stillborn baby. Although parents are aware of the sibling's situation, they feel that they are left somewhat alone in their parenthood after stillbirth and therefore need support and guidance from others. (BIRTH 38:2 June 2011).</p

Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity

SummaryObjectiveAlthough available nonsurgical pharmacotherapies for treatment of osteoarthritis (OA) are considered to be solely symptom-modifying agents, recent advances have been made in the search for agents that may modify disease progression. Intra-articular hyaluronan (HA) therapy is one symptom-modifying approach that has been found to be safe and effective for reducing pain due to OA of the knee. Presented here is a review of the evidence that HAs may also modify the rate of OA disease progression in addition to providing symptomatic efficacy.DesignA review of the literature based on a MEDLINE search through June 2004, using the terms HA, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20, OA, disease modification, structure modifying and joint structure.ResultsEvidence for disease-modifying activity of HAs stems from 1) the complex biochemical effects of HAs in the synovium and extracellular matrix of the articular cartilage, including interactions between exogenously administered HA and articular cartilage, subchondral bone, matrix proteoglycans, and collagens; 2) the effects of HA administration in animal models of OA, including total or partial meniscectomy and anterior cruciate ligament transectomy; 3) results of clinical trials using one HA, Hyalgan® (sodium hyaluronate, molecular weight 500–730kDa) that evaluated structural outcomes, such as joint-space width, chondrocyte density and vitality, and arthroscopic evaluation of chondropathy.DiscussionGrowing preclinical and clinical evidence supports the notion that, in addition to relieving the symptoms of OA, HAs also modify the structure of the diseased joint and the rate of OA disease progression, at least early in the evolution of the disease process

Biology and conservation of Zerynthia cassandra (Lepidoptera, Papilionidae) in semi-natural environments and agricultural landscapes

The Southern festoon, Zerynthia polyxena, is a south-European butterfly listed in Annex IV of the Habitats Directive (92/43/EEC). Populations from most of the Italian territory have been recently recognized as belonging to a separate species, endemic to Italy: Zerynthia cassandra. In the province of Bologna (northern Italy), Z. cassandra is quite common. The territory of the province is densely inhabited and modified by man. Semi-natural environments are found almost exclusively in the hills, while the plain is almost entirely built-upon or cultivated. This study was based on data collected in the field in the province of Bologna, and aimed to investigate some biological and ecological aspects of Z. cassandra, with the purpose of identifying the factors that favour its presence and the most relevant issues for its conservation. In the area of study, the hostplant of Z. cassandra is Aristolochia rotunda, which is common in the plain, along the edges of drainage canals, where it supports a large Z. cassandra population. In the hills, A. rotunda is scarcer, and Z. cassandra is present in small separated nodes. Human activities such as mowing and canal maintenance are potentially damaging to Z. cassandra, particularly if carried out when eggs and larvae are present. However, if correctly timed and executed, such maintenance can preserve grassy areas that would otherwise be colonized by bushes and trees, and in which A. rotunda finds a suitable environment. Some level of disturbance can be beneficial for Z. cassandra habitats, favouring the species’ survival in the long term