Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation

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). 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. 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. 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. 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. 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.

Prevalence and risk factors for stunting and severe stunting among under-fives in North Maluku province of Indonesia

BACKGROUND: Adequate nutrition is needed to ensure optimum growth and development of infants and young children. Understanding of the risk factors for stunting and severe stunting among children aged less than five years in North Maluku province is important to guide Indonesian government public health planners to develop nutrition programs and interventions in a post conflict area. The purpose of the current study was to assess the prevalence of and the risk factors associated with stunting and severe stunting among children aged less than five years in North Maluku province of Indonesia. METHODS: The health and nutritional status of children aged less than five years was assessed in North Maluku province of Indonesia in 2004 using a cross-sectional multi-stage survey conducted on 750 households from each of the four island groups in North Maluku province. A total of 2168 children aged 0-59 months were used in the analysis. RESULTS: Prevalence of stunting and severe stunting were 29% (95%CI: 26.0-32.2) and 14.1% (95%CI: 11.7-17.0) for children aged 0-23 months and 38.4% (95%CI: 35.9-41.0) and 18.4% (95%CI: 16.1-20.9) for children aged 0-59 months, respectively. After controlling for potential confounders, multivariate analysis revealed that the risk factors for stunted children were child's age in months, male sex and number of family meals per day (

Tenocyte responses to mechanical loading in vivo : A role for local insulin-like growth factor 1 signaling in early tendinosis in rats

Objective
To investigate tenocyte regulatory events during the development of overuse supraspinatus tendinosis in rats.

Methods
Supraspinatus tendinosis was induced by running rats downhill at 1 km/hour for 1 hour a day. Tendons were harvested at 4, 8, 12, and 16 weeks and processed for brightfield, polarized light, or transmission electron microscopy. The development of tendinosis was assessed semiquantitatively using a modified Bonar histopathologic scale. Apoptosis and proliferation were examined using antibodies against fragmented DNA or proliferating cell nuclear antigen, respectively. Insulin-like growth factor 1 (IGF-1) expression was determined by computer-assisted quantification of immunohistochemical reaction. Local IGF-1 signaling was probed using antibodies to phosphorylated insulin receptor substrate 1 (IRS-1) and ERK-1/2.

Results
Tendinosis was present after 12 weeks of downhill running and was characterized by tenocyte rounding and proliferation as well as by glycosaminoglycan accumulation and collagen fragmentation. The proliferation index was elevated in CD90+ tenocytes in association with tendinosis and correlated with increased local IGF-1 expression by tenocytes and phosphorylation of IRS-1 and ERK-1/2. Both apoptosis and cellular inflammation were absent at all time points.

Conclusion
In this animal model, early tendinosis was associated with local stimulation of tenocytes rather than with extrinsic inflammation or apoptosis. Our data suggest a role for IGF-1 in the load-induced tenocyte responses during the pathogenesis of overuse tendon disorders.

Job stress as a preventable upstream determinant of common mental disorders: a review for practitioners and policy-makers

There is growing recognition of the important role of mental health in the workforce and in the workplace. At the same time, there has been a rapid growth of studies linking job stress and other psychosocial working conditions to common mental disorders, and a corresponding increase in public concern media attention to job stress and its impact upon worker health and well-being. This article provides a summary of the relevant scientific and medical literature on this topic for practitioners and policy-makers. It presents a primer on job stress concepts, an overview of the evidence linking job stress and common mental disorders, a summary of the intervention research on ways to prevent and control job stress, and a discussion of the strengths and weakness of the evidence base. We conclude that there is strong evidence linking job stress and common mental disorders, and that it is a substantial problem on the population level. On a positive note, however, the job stress intervention evidence also shows that the problem is preventable and can be effectively addressed by a combination of work- and worker-directed intervention.

Analysis of circadian rhythms from online communities of individuals with affective disorders

The circadian system regulates 24 hour rhythms in biological creatures. It impacts mood regulation. The disruptions of circadian rhythms cause destabilization in individuals with affective disorders, such as depression and bipolar disorders. Previous work has examined the role of the circadian system on effects of light interactions on mood-related systems, the effects of light manipulation on brain, the impact of chronic stress on rhythms. However, such studies have been conducted in small, preselected populations. The deluge of data is now changing the landscape of research practice. The unprecedented growth of social media data allows one to study individual behavior across large and diverse populations. In particular, individuals with affective disorders from online communities have not been examined rigorously. In this paper, we aim to use social media as a sensor to identify circadian patterns for individuals with affective disorders in online communities.We use a large scale study cohort of data collecting from online affective disorder communities. We analyze changes in hourly, daily, weekly and seasonal affect of these clinical groups in contrast with control groups of general communities. By comparing the behaviors between the clinical groups and the control groups, our findings show that individuals with affective disorders show a significant distinction in their circadian rhythms across the online activity. The results shed light on the potential of using social media for identifying diurnal individual variation in affective state, providing key indicators and risk factors for noninvasive wellbeing monitoring and prediction.

Sarcopenia and the common mental disorders: a potential regulatory role of skeletal muscle on brain function?

While it is understood that body composition impacts on physical conditions, such as diabetes and cardiovascular disease, it is only now apparent that body composition might play a role in the genesis of common mental disorders, depression and anxiety. Sarcopenia occurs in ageing and comprises a progressive decline in muscle mass, strength and function, leading to frailty, decreased independence and poorer quality of life. This review presents an emerging body of evidence to support the hypothesis that shared pathophysiological pathways for sarcopenia and the common mental disorders constitute links between skeletal muscle and brain function. Contracting skeletal muscle secretes neurotrophic factors that are known to play a role in mood and anxiety, and have the dual role of nourishing neuronal growth and differentiation, while protecting the size and number of motor units in skeletal muscle. Furthermore, skeletal muscle activity has important immune and redox effects that impact behaviour and reduce muscle catabolism.