Comparing initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care: A study of Irish National data.

BACKGROUND: The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. OBJECTIVES: To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. METHODS: Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. RESULTS: Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. CONCLUSION: This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].

Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.

CONTEXT: Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown. OBJECTIVE: To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons. DESIGN, SETTING, AND PARTICIPANTS: A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998. INTERVENTIONS: Participants were randomized to receive GH (starting dose, 30 micro g/kg, reduced to 20 micro g/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 micro g/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design. MAIN OUTCOME MEASURES: Lean body mass, fat mass, muscle strength, maximum oxygen uptake (VO(2)max) during treadmill test, and adverse effects. RESULTS: In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P =.09), 1.0 kg with GH (P =.001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P =.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P =.09), GH (P =.29), and GH + HRT (P =.14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P =.05). Women's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P =.07) and GH + HRT (P =.06). Men's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P =.49) but increased with GH (P =.11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in VO(2)max (r = 0.320; P =.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P =.006). CONCLUSIONS: In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and VO( 2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies.

Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men.

BACKGROUND: Aging is associated with concomitant declines in activity of the growth hormone (GH) and gonadal steroid axes, and in bone mineral density (BMD), in both sexes. Long-term estrogen replacement slows bone loss and prevents fractures in postmenopausal women, whereas the effects of supplementation of GH or testosterone on bone metabolism and BMD in aged individuals remains uncertain. METHODS: Using a randomized, placebo-controlled, double-blind study design, we investigated the separate and interactive effects of 6 months of administration of recombinant human GH and/or gonadal steroids on bone biochemical markers and BMD in 125 healthy, older (>65 years) women (n = 53) and men (n = 72) with age-related reductions in GH and gonadal steroids. RESULTS: In women, administration of GH, but not GH + hormone replacement therapy (HRT), increased serum levels of osteocalcin and procollagen peptide (PICP) and increased urinary excretion of deoxypyridinoline (DPD) crosslinks. Urinary calcium excretion decreased after HRT. In men, GH, and to a greater extent GH + T, increased osteocalcin. GH increased serum PICP, and GH + T increased urinary DPD. Urinary calcium excretion was unaffected by hormone treatment in men. In women, administration of HRT and GH + HRT, but not GH, increased BMD at the lumbar spine, femoral neck, and distal radius. In men, GH + T led to a small decrease in BMD at the proximal radius; there were no other significant effects of hormone administration on BMD. CONCLUSIONS: These data suggest that short-term administration of HRT exerts beneficial effects on bone metabolism and BMD in postmenopausal women, which are not significantly altered by the coadministration of GH. In andropausal men, T administration to achieve physiologic levels did not result in significant effects on bone metabolism or BMD, whereas GH + T increased one marker of bone formation and decreased one marker of bone resorption. Given the known biphasic actions of GH on bone and the apparent favorable biochemical effects of GH + T in men, the longer-term effects of GH + T on BMD in aged men remain to be clarified.