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Health Policy (Amsterdam, Netherlands) Jul 2015Cost-of-illness studies, the systematic quantification of the economic burden of diseases on the individual and on society, help illustrate direct budgetary consequences... (Review)
Review
Cost-of-illness studies, the systematic quantification of the economic burden of diseases on the individual and on society, help illustrate direct budgetary consequences of diseases in the health system and indirect costs associated with patient or carer productivity losses. In the context of the BURQOL-RD project ("Social Economic Burden and Health-Related Quality of Life in patients with Rare Diseases in Europe") we studied the evidence on direct and indirect costs for 10 rare diseases (Cystic Fibrosis [CF], Duchenne Muscular Dystrophy [DMD], Fragile X Syndrome [FXS], Haemophilia, Juvenile Idiopathic Arthritis [JIA], Mucopolysaccharidosis [MPS], Scleroderma [SCL], Prader-Willi Syndrome [PWS], Histiocytosis [HIS] and Epidermolysis Bullosa [EB]). A systematic literature review of cost of illness studies was conducted using a keyword strategy in combination with the names of the 10 selected rare diseases. Available disease prevalence in Europe was found to range between 1 and 2 per 100,000 population (PWS, a sub-type of Histiocytosis, and EB) up to 42 per 100,000 population (Scleroderma). Overall, cost evidence on rare diseases appears to be very scarce (a total of 77 studies were identified across all diseases), with CF (n=29) and Haemophilia (n=22) being relatively well studied, compared to the other conditions, where very limited cost of illness information was available. In terms of data availability, total lifetime cost figures were found only across four diseases, and total annual costs (including indirect costs) across five diseases. Overall, data availability was found to correlate with the existence of a pharmaceutical treatment and indirect costs tended to account for a significant proportion of total costs. Although methodological variations prevent any detailed comparison between conditions and based on the evidence available, most of the rare diseases examined are associated with significant economic burden, both direct and indirect.
Topics: Cost of Illness; Europe; Health Care Costs; Humans; Orphan Drug Production; Prevalence; Quality of Life; Rare Diseases
PubMed: 25661982
DOI: 10.1016/j.healthpol.2014.12.016 -
Research in Developmental Disabilities Aug 2014Over the past three decades, the potential effects of lifestyle interventions targeting changes in body weight and composition (weight, body mass index, fat mass, waist... (Review)
Review
Over the past three decades, the potential effects of lifestyle interventions targeting changes in body weight and composition (weight, body mass index, fat mass, waist circumference) among adults with an intellectual disability (ID) have been examined in various systematic reviews. Nevertheless, since the middle of the 1980s, the potential effects of these interventions for youth with an ID remain an open question. The purpose of this article is to review the effects of lifestyle interventions targeting changes in body weight and composition among youth with an ID. This review will focus on changes in body weight and composition, healthy lifestyle, and secondary health conditions. A systematic review of English- and French-language studies, published between 1981 and 2013, was performed on Academic Search Complete, PsycARTICLES, Medline and Scopus. The nine studies included in this review focused mainly on: a sample with a wide age range (e.g., 7-22 years); males; overweight-obese youth having a mild-to-moderate ID with Down or Prader-Willi syndrome; physical activity interventions; cohort pre- and post-test designs with/without a control group; and changes in body weight and composition. Taken together, results from these studies suggest successful changes in weight, body mass index and fat mass. However, intervention effects on healthy lifestyle and secondary health conditions are scarce and inconclusive. Given the weaknesses of the reviewed studies, the present findings should be considered preliminary and indicative of the need for future research.
Topics: Adiposity; Body Composition; Body Weight; Health Promotion; Humans; Intellectual Disability; Life Style
PubMed: 24830882
DOI: 10.1016/j.ridd.2014.04.014 -
Genetics and Molecular Research : GMR Mar 2014Prader-Willi syndrome (PWS) is caused by the lack of expression of genes located on paternal chromosome 15q11-q13. This lack of gene expression may be due to a deletion... (Meta-Analysis)
Meta-Analysis Review
Prader-Willi syndrome (PWS) is caused by the lack of expression of genes located on paternal chromosome 15q11-q13. This lack of gene expression may be due to a deletion in this chromosomal segment, to maternal uniparental disomy of chromosome 15, or to a defect in the imprinting center on 15q11-q13. PWS is characterized by hypotonia during the neonatal stage and in childhood, accompanied by a delay in neuropsychomotor development. Overeating, obesity, and mental deficiency arise later on. The syndrome has a clinical overlap with other diseases, which makes it difficult to accurately diagnose. The purpose of this article is to review the Prader-Willi-like phenotype in the scientific literature from 2000 to 2013, i.e., to review the cases of PWS caused by chromosomal abnormalities different from those found on chromosome 15. A search was carried out using the "National Center for Biotechnology Information" (www.pubmed.com) and "Scientific Electronic Library Online (www.scielo.br) databases and combinations of key words such as "Prader-Willi-like phenotype" and "Prader-Willi syndrome phenotype". Editorials, letters, reviews, and guidelines were excluded. Articles chosen contained descriptions of patients diagnosed with the PWS phenotype but who were negative for alterations on 15q11-q13. Our search found 643 articles about PWS, but only 14 of these matched with the Prader-Willi-like phenotype and with the selected years of publication (2000-2013). If two or more articles reported the same chromosomal alterations for Prader-Willi-like phenotype, the most recent was chosen. Twelve articles of 14 were case reports and 2 reported series of cases.
Topics: Chromosome Aberrations; Diagnosis, Differential; Female; Humans; Male; Phenotype; Prader-Willi Syndrome
PubMed: 24737477
DOI: 10.4238/2014.March.31.9 -
Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents.The Journal of Clinical Endocrinology... May 2014Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may... (Review)
Review
OBJECTIVE
Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence.
METHODS
We searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included.
RESULTS AND CONCLUSIONS
Total ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.
Topics: Adolescent; Body Weight; Child; Child, Preschool; Eating; Ghrelin; Humans; Obesity; Postprandial Period
PubMed: 24601727
DOI: 10.1210/jc.2013-4010 -
The Journal of Clinical Endocrinology... Jun 2013Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in... (Review)
Review
CONTEXT
Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events.
OBJECTIVE
The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS.
EVIDENCE
We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries.
METHODOLOGY
Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN).
CONCLUSIONS
Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.
Topics: Adult; Child; Human Growth Hormone; Humans; Infant; Practice Guidelines as Topic; Prader-Willi Syndrome; Recombinant Proteins; Treatment Outcome
PubMed: 23543664
DOI: 10.1210/jc.2012-3888 -
Frontiers in Neuroendocrinology Apr 2013Prader-Willi Syndrome (PWS) is a neurodevelopmental genetic disorder caused by loss of expression of imprinted, paternally inherited genes on chromosome 15q11q13. This... (Review)
Review
Prader-Willi Syndrome (PWS) is a neurodevelopmental genetic disorder caused by loss of expression of imprinted, paternally inherited genes on chromosome 15q11q13. This imprinted gene cluster has its homologous region on mouse chromosome 7C. The extremely well conserved synteny between the human and the murine regions gave origin to the generation of mouse models for PWS, which facilitated investigations of the role and function of single genes or gene clusters in the pathogenesis of this disease. In this review we will describe which mouse models have been generated so far and how they were developed; we will focus on the consequences of single genes' (or gene clusters') loss of expression on the phenotype, highlighting the similarities to the human PWS features. PWS mouse models have brought major improvements in our knowledge about this complex condition, although the mechanisms implicated in its pathogenesis still remain not fully understood.
Topics: Animals; Antigens, Neoplasm; Chromosome Mapping; Chromosomes, Human, Pair 15; Disease Models, Animal; Genomic Imprinting; Humans; Mice; Mice, Knockout; Multigene Family; Nerve Tissue Proteins; Nuclear Proteins; Prader-Willi Syndrome; Proteins; RNA, Small Nucleolar; Synteny; snRNP Core Proteins
PubMed: 23391702
DOI: 10.1016/j.yfrne.2013.01.002 -
Neuroscience and Biobehavioral Reviews Sep 2012Although motor problems in Prader-Willi syndrome (PWS) are prominent in infants, and continue into childhood and adulthood, there is little insight into the factors... (Review)
Review
Although motor problems in Prader-Willi syndrome (PWS) are prominent in infants, and continue into childhood and adulthood, there is little insight into the factors important for clinical management. The literature was reviewed to: (1) provide an overview of the characteristics and prevalence of motor problems and (2) evaluate the effects of growth hormone (GH) treatment and physical training on motor performance. A systematic search revealed 34 papers: 13 on motor performance; 12 on GH treatment; and nine on physical training. In infants, motor development is 30-57% of the normal reference values, and children and adults also have significant problems in skill acquisition, muscle force, cardiovascular fitness, and activity level. GH treatment positively influenced motor performance in infants, children, and adults, although not all studies demonstrated an effect. All studies on physical training demonstrated beneficial effects in PWS patients. We suggest a combination of GH treatment and physical training to be started as soon as possible, especially in infants, to improve motor development as this will positively influence general development.
Topics: Animals; Body Composition; Human Growth Hormone; Humans; Motor Activity; Prader-Willi Syndrome; Treatment Outcome
PubMed: 22652271
DOI: 10.1016/j.neubiorev.2012.05.005 -
Korean Journal of Pediatrics Feb 2011Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome...
Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. This syndrome has a characteristic phenotype including severe neonatal hypotonia, early-onset hyperphagia, development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioral problems, and psychiatric problems. PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect. Over 99% of PWS cases can be diagnosed using DNA methylation analysis. Early diagnosis of PWS is important for effective long-term management. Growth hormone (GH) treatment improves the growth, physical phenotype, and body composition of patients with PWS. In recent years, GH treatment in infants has been shown to have beneficial effects on the growth and neurological development of patients diagnosed during infancy. There is a clear need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy in patients with PWS.
PubMed: 21503198
DOI: 10.3345/kjp.2011.54.2.55 -
Neuroscience and Biobehavioral Reviews Jan 2011Motor problems in Prader-Willi syndrome (PWS) are presumably related to abnormal body composition and certain neuromuscular abnormalities. The authors reviewed the... (Review)
Review
Motor problems in Prader-Willi syndrome (PWS) are presumably related to abnormal body composition and certain neuromuscular abnormalities. The authors reviewed the literature to evaluate the extent to which body composition is affected and gathered all findings on neuromuscular functioning in PWS. A systematic review was conducted in four databases (1956-2010). The methodological quality of each included article was evaluated. Thirty-eight papers were included: body composition (9 studies), neuromuscular functioning (7) and growth hormone (GH) effect studies (23). Increased fat mass and decreased lean body mass are characteristics of PWS. As a result, muscle mass is decreased by 25-37%, which might explain partly the weakness and hypotonia. However, there are also structural and functional muscle abnormalities, and cortical motor areas are hypo-excitable in PWS patients. Moreover, disuse as result of decreased activity in PWS could also contribute. GH treatment positively influences body composition, but does not normalize it. Training could prevent disuse and improves body composition. Therefore GH treatment and training will probably enhance one another.
Topics: Body Composition; Humans; Movement Disorders; Neuromuscular Junction; Prader-Willi Syndrome
PubMed: 21056055
DOI: 10.1016/j.neubiorev.2010.10.015 -
Health Technology Assessment... Sep 2010Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS),... (Review)
Review
BACKGROUND
Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), short stature homeobox-containing gene deficiency (SHOX-D) and being born small for gestational age (SGA).
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of rhGH compared with treatment strategies without rhGH for children with GHD, TS, PWS, CRI, SHOX-D and those born SGA.
DATA SOURCES
The systematic review used a priori methods. Key databases were searched (e.g. MEDLINE, EMBASE, NHS Economic Evaluation Database and eight others) for relevant studies from their inception to June 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK.
STUDY SELECTION
Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers, and screened them against inclusion criteria.
STUDY APPRAISAL
Data from included studies were extracted by one reviewer and checked by a second. Quality of included studies was assessed using standard criteria, applied by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through a narrative review.
RESULTS
Twenty-eight randomised controlled trials (RCTs) in 34 publications were included in the systematic review. GHD: Children in the rhGH group grew 2.7 cm/year faster than untreated children and had a statistically significantly higher height standard deviation score (HtSDS) after 1 year: -2.3 ± 0.45 versus -2.8 ± 0.45. TS: In one study, treated girls grew 9.3 cm more than untreated girls. In a study of younger children, the difference was 7.6 cm after 2 years. HtSDS values were statistically significantly higher in treated girls. PWS: Infants receiving rhGH for 1 year grew significantly taller (6.2 cm more) than those untreated. Two studies reported a statistically significant difference in HtSDS in favour of rhGH. CRI: rhGH-treated children in a 1-year study grew an average of 3.6 cm more than untreated children. HtSDS was statistically significantly higher in treated children in two studies. SGA: Criteria were amended to include children of 3+ years with no catch-up growth, with no reference to mid-parental height. Only one of the RCTs used the licensed dose; the others used higher doses. Adult height (AH) was approximately 4 cm higher in rhGH-treated patients in the one study to report this outcome, and AH-gain SDS was also statistically significantly higher in this group. Mean HtSDS was higher in treated than untreated patients in four other studies (significant in two). SHOX-D: After 2 years' treatment, children were approximately 6 cm taller than the control group and HtSDS was statistically significantly higher in treated children. The incremental cost per quality adjusted life-year (QALY) estimates of rhGH compared with no treatment were: 23,196 pounds for GHD, 39,460 pounds for TS, 135,311 pounds for PWS, 39,273 pounds for CRI, 33,079 pounds for SGA and 40,531 pounds for SHOX-D. The probability of treatment of each of the conditions being cost-effective at 30,000 pounds was: 95% for GHD, 19% for TS, 1% for PWS, 16% for CRI, 38% for SGA and 15% for SHOX-D.
LIMITATIONS
Generally poorly reported studies, some of short duration.
CONCLUSIONS
Statistically significantly larger HtSDS values were reported for rhGH-treated children with GHD, TS, PWS, CRI, SGA and SHOX-D. rhGH-treated children with PWS also showed statistically significant improvements in body composition measures. Only treatment of GHD would be considered cost-effective at a willingness-to-pay threshold of 20,000 to 30,000 pounds per QALY gained. This analysis suggests future research should include studies of longer than 2 years reporting near-final height or final adult height.
Topics: Biomarkers; Body Composition; Cost-Benefit Analysis; Dwarfism, Pituitary; Growth Disorders; Human Growth Hormone; Humans; Incidence; Linear Models; Models, Economic; Prevalence; Prognosis; Quality Assurance, Health Care; Quality of Life; Quality-Adjusted Life Years; United States
PubMed: 20849734
DOI: 10.3310/hta14420