Treatment of hypogonadal adolescent boys with long acting subcutaneous testosterone pellets

AIMS: Long acting subcutaneous testosterone pellets are of proved efficacy for the treatment of hypogonadal men, but have not been reported as a treatment modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone release have shown prolonged normalisation of testosterone levels for at least four months. Administration of a long acting, safe, effective, and convenient form of treatment is desirable when life-long treatment is indicated. PATIENTS AND METHODS: Eighteen boys (aged 13.9-17.5 years at the start of treatment)-seven with primary hypogonadism, nine with secondary hypogonadism, and two boys being treated with testosterone for tall stature--were given testosterone pellets (8-10 mg/kg) every six months for 18 months. Height, weight, pubertal status, and psychosocial parameters were assessed and follicle stimulating hormone, luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1, 3, 6, 12, and 18 months. Bone age was measured at 0 and 12 months. RESULTS: In all boys growth velocity continued appropriately for bone age. Puberty continued to progress in all boys and in two boys the amount of virilisation exceeded that seen with previous treatment with intramuscular testosterone. After testosterone administration, follicle stimulating hormone and luteinising hormone suppressed incompletely in the boys with primary hypogonadism. Serum testosterone ranged from 4.3 to 26.7 nmol/l at three months to less than 10 nmol/l at six months after implantation. Prolactin and lipid levels were normal throughout the study. By report, there was an improvement in mood and emotional wellbeing. No pellet extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS: All boys preferred this mode of testosterone administration to intramuscular injections. Long acting subcutaneous testosterone pellets are safe, efficacious, well tolerated, and convenient, and result in normal physical growth and improved psychological outlook in adolescent hypogonadal boys.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Outcome for older burn patients

BACKGROUND: Physicians will be increasingly responsible for an aging society whose members demonstrate a notable striving for independence. HYPOTHESIS: With standard treatment of burns, older patients will have a survival rate of more than 70%, with at least 60% of patients becoming fully functional 6 months after hospital discharge. METHODS: A 7-year retrospective medical review of burn unit patients was performed, and 221 ( 11%) of 1957 patients who were at least 59 years old were identified. RESULTS: Of 97 women (44%) and 124 men (56%), 64 (29%) had an associated smoke inhalation injury; 146 (66%), flame injury; and 44 (20%), scald injury. The bedroom and/or living room were the most common areas of injury (90 [41%]), followed by outdoors and the workplace (62 [28%]), the kitchen (40 [18%]), the bathroom ( 18 [8%]), and the garage or basement (11 [5%]) (P<.005). One hundred twenty-six injuries (57%) were associated with impaired judgment, mobility, or both. On hospital admission, 74 patients (36%) were intubated, 60 (30%) required intubation postoperatively, and 34 (18%) required both. The survival rate was 159 patients (72%) overall. Findings from an ethanol screening and a drug toxicology screening were positive in 22 and 32 patients (10% and 29%) on admission, respectively. Of the survivors, most were discharged to home with (87 [64%) or without visiting nurse supervision, and at 6 months after discharge, 16 patients (50%) in transitional care facilities were able to return to an independent level of functioning. Of the 59- to 69-year-old age group, 83 (86%) survived compared with 59 (69%) in the 70- to 79-year-old age group and 18 (47%) in the 80 years and older age group. CONCLUSIONS: In contrast to the usual male preponderance in patients with thermal injury, older women, many of whom are widowed, constituted almost half of the older patients admitted to the hospital. Modalities for injury prevention are necessary to provide optimal and safe household environments for a growing population of older persons.     

The effects of noise in cardiac diffusion tensor imaging and the benefits of averaging complex data

There is growing interest in cardiac diffusion tensor imaging (cDTI), but, unlike other diffusion MRI applications, there has been little investigation of the effects of noise on the parameters typically derived. One method of mitigating noise floor effects when there are multiple image averages, as in cDTI, is to average the complex rather than the magnitude data, but the phase contains contributions from bulk motion, which must be removed first. The effects of noise on the mean diffusivity (MD), fractional anisotropy (FA), helical angle (HA) and absolute secondary eigenvector angle (E2A) were simulated with various diffusion weightings (b values). The effect of averaging complex versus magnitude images was investigated. In vivo cDTI was performed in 10 healthy subjects with b = 500, 1000, 1500 and 2000 s/mm². A technique for removing the motion‐induced component of the image phase present in vivo was implemented by subtracting a low‐resolution copy of the phase from the original images before averaging the complex images. MD, FA, E2A and the transmural gradient in HA were compared for un‐averaged, magnitude‐ and complex‐averaged reconstructions. Simulations demonstrated an over‐estimation of FA and MD at low b values and an under‐estimation at high b values. The transition is relatively signal‐to‐noise ratio (SNR) independent and occurs at a higher b value for FA (b = 1000–1250 s/mm²) than MD (b ≈ 250 s/mm²). E2A is under‐estimated at low and high b values with a transition at b ≈ 1000 s/mm², whereas the bias in HA is comparatively small. The under‐estimation of FA and MD at high b values is caused by noise floor effects, which can be mitigated by averaging the complex data. Understanding the parameters of interest and the effects of noise informs the selection of the optimal b values. When complex data are available, they should be used to maximise the benefit from the acquisition of multiple averages. The combination of complex data is also a valuable step towards segmented acquisitions. Copyright © 2016 John Wiley & Sons, Ltd.     

Use of retail data in the assessment of natural experiments: the case of Reducing the Strength,an intervention to reduce alcohol availability

BackgroundRetailers routinely collect data about people's purchasing behaviours and access to consumer products associated with health and wellbeing. Here we discuss how retail data can be used in public health research and consider potential strengths and limitations to such research. To illustrate the discussion we refer to an evaluation of an intervention called Reducing the Strength, whereby off-licence shops and supermarkets voluntarily stopped selling inexpensive superstrength (≥6·5% alcohol by volume) beers and ciders.MethodsMonthly data from a large retail chain (East of England Co-operative Society) were obtained for three UK counties (141 stores). In one county the intervention started 12 months earlier than the others, allowing for a pre–post study design with a delayed implementation comparator. Difference-in-differences analysis of unit alcohol sales controlled for socioenvironmental confounders and shop-level characteristics including shop size, parking facilities, cash machines, opening hours, and other factors.FindingsThe retail data detailed shop-level characteristics and sales data such as prices, quantities, product brands, alcohol content, sales, and factors affecting sales. The wide geographical coverage, shop-level data, including data for potential confounding factors, and frequent timepoints made the retail data well-suited for a quasi-experimental evaluation capitalising on temporal and spatial variations in intervention exposure. Limitations of this study include a lack of longitudinal data for individual customers, and shops that are not covered by the data. Qualitative interviews with shop workers and customers, and triangulation using alternative data sources can help to address limitations. Alternative sources of retail data such as private sector consultants who specialise in collecting shop-level and sales data for a range of companies might also address some limitations; however, there are potential barriers of expense, accessibility, and coverage associated with the use of such consultants.InterpretationIncreasingly, researchers recognise the potential of retail data for evaluating interventions affecting social determinants of health and inequalities, such as local access to alcohol. However, shop-level data have frequently proved difficult for researchers to obtain. By obtaining such data we have been able to assess, using a quasi-experimental design, the effects of removing strong, cheap beers and ciders from shops. We have also been able to explore in more detail how to optimise the strengths and address some limitations of the data in ways that could potentially assist others planning to use this important data source in their research.FundingThe study is funded as part of the School of Public Health Research by NHS National Institute of Health Research. AJ, SA, and JW contributed as employees of Public Health Suffolk, Suffolk County Council.