Evaluation of two health status measures in adults with growth hormone deficiency

Objective: To evaluate the psychometric properties of two health status measures for adults with growth hormone deficiency (GHD): Nottingham Health Profile (NHP) and Short Form Health Survey (SF-36). Design: (1) A cross-sectional survey of adults with treated or untreated GHD, to assess reliability and validity of the questionnaires. (2) A randomised, placebo-controlled study of 3 months’ GH withdrawal from GH-treated adults, to assess the questionnaires’ sensitivity to change. Patients: (1) Cross-sectional survey of 157 patients with severe GHD (peak GH Measurements: The NHP and SF-36 were used once in the cross-sectional survey, but twice in the GH-withdrawal study, at baseline and end-point (after 3 months). Results: (1) Cross-sectional survey. Both questionnaires had high internal consistency reliability with subscale Cronbach’s alphas of > 0.73 (NHP) and > 0.78 (SF 36). Calculation of a NHP Total score, occasionally reported in the literature, was shown to be inadvisable. Overall, patients with GHD were found to have significantly worse perceived functioning than the UK general population in SF 36 subscales of General Health, Pain, Social Functioning, Role-Emotional, Role-Physical, and Vitality. Whilst neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations with duration of GH treatment (p Conclusions: The SF-36 is a better measure than the NHP of health status of people with GHD, owing to its greater discriminatory power with ability to detect lesser degrees of disability. It also has superior sensitivity to some sub-group differences and superior sensitivity to change than the NHP. The SF-36 is highly acceptable to respondents, and has very good internal consistency reliability. The SF-36 is recommended to measure the health status of adults with GHD

Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency.

Objective: Growth hormone (GH) is known to be required for physical well-being. Whilst it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD). Design: A double-blind, placebo-controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH-deficient adults, where 9 continued with GH replacement. Patients: GH-treated adults (10 men, 11 women), all with severe GHD (peak GH Measurements: Semi-structured interviews were given at baseline and end-point plus questionnaires that included a new hormone-deficiency specific, individualised, QoL questionnaire (HDQoL), the General Well-being Index (GWBI), the Well-being Questionnaire (W-BQ12), Short-Form 36 health status questionnaire (SF-36), the Nottingham Health Profile NHP) and the General Health Questionnaire (GHQ). Results: Three months after baseline the serum total IGF-I of placebo-treated patients fell from normal, age related levels (mean 26.6 ± 13.2 nmol/ L) to levels indicative of severe GHD (11.6 ± 6.6 nmol/ L) (P Conclusion: Withdrawal of GH-treatment from adults with severe GHD has detrimental psychological effects

Brain structure and neurocognitive function in two professional mountaineers during 35 days of severe normobaric hypoxia

Background and purpose Animal studies suggest that exposure to severe ambient hypoxia for several days may have beneficial long-term effects on neurodegenerative diseases. Because, the acute risks of exposing human beings to prolonged severe hypoxia on brain structure and function are uncertain, we conducted a pilot study in healthy persons. Methods We included two professional mountaineers (participants A and B) in a 35-day study comprising an acclimatization period and 14 consecutive days with oxygen concentrations between 8% and 8.8%. They underwent cerebral magnetic resonance imaging at seven time points and a cognitive test battery covering a spectrum of cognitive domains at 27 time points. We analysed blood neuron specific enolase and neurofilament light chain levels before, during, and after hypoxia. Results In hypoxia, white matter volumes increased (maximum: A, 4.3% ± 0.9%; B, 4.5% ± 1.9%) whilst gray matter volumes (A, −1.5% ± 0.8%; B, −2.5% ± 0.9%) and cerebrospinal fluid volumes (A, −2.7% ± 2.4%; B, −5.9% ± 8.2%) decreased. Furthermore, the number (A, 11–17; B, 26–126) and volumes (A, 140%; B, 285%) of white matter hyperintensities increased in hypoxia but had returned to baseline after a 3.5-month recovery phase. Diffusion weighted imaging of the white matter indicated cytotoxic edema formation. We did not observe changes in cognitive performance or biochemical brain injury markers. Discussion In highly selected healthy individuals, severe sustained normobaric hypoxia over 2 weeks elicited reversible changes in brain morphology without clinically relevant changes in cognitive function or brain injury markers. The finding may pave the way for future translational studies assessing the therapeutic potential of hypoxia in neurodegenerative diseases

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Non-standard errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants