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BackgroundMedical abortion provided via telemedicine is becoming more widely available, potentially decreasing travel time for in-person abortion evaluation.MethodsWe conducted a retrospective chart review of all outpatient medical abortions from October 2016 through December 2019 at our academic medical centre in Portland, Oregon, USA. Using mifepristone administration logs, we identified patients who underwent abortion via direct-to-patient telemedicine or in clinic. Both groups had pre-abortion ultrasound examination. We extracted patient characteristics and geographic data to compare travel distance to clinic, ultrasound facility, and nearest advertised abortion clinic. We compared time from first contact until mifepristone ingestion and gestational age at mifepristone ingestion.ResultsMedian distance from mailing address to clinic for 80 telemedicine and 124 clinic medical abortions was 95 (range 4–377) and 12 (range 0–184) miles (p200 miles. Distance to nearest advertised abortion clinic was equal between groups (median 7 miles, p=0.4). Time to mifepristone administration (ingestion) was longer (11 vs 6 days; pConclusionsTelemedicine increases the reach of abortion providers and provides care to more geographically distant patients. Patients chose telemedicine abortion even when they had an equidistant option, suggesting that patients value telemedicine for reasons other than geographic convenience. This telemedicine delivery model that included ultrasound testing prior to abortion resulted in up to a 5-day delay in abortion initiation, which was not clinically significant.

Contains fulltext : 235257.pdf (Publisher’s version ) (Open Access) AIMS: Adolescents and young adults aged 15-39 years with cancer face unique medical, practical and psychosocial issues. In the UK, principal treatment centres and programmes have been designed to care for teenage and young adult patients aged 13-24 years in an age-appropriate manner. However, for young adults (YAs) aged 25-39 years with cancer, little access to age-specific support is available. The aim of this study was to examine this possible gap by qualitatively exploring YA care experiences, involving patients as research partners in the analysis to ensure robust results. MATERIALS AND METHODS: We conducted a phenomenological qualitative study with YAs diagnosed with any cancer type between ages 25 and 39 years old in the last 5 years. Participants took part in interviews or focus groups and data were analysed using inductive thematic analysis. Results were shaped in an iterative process with the initial coders and four YA patients who did not participate in the study to improve the rigor of the results. RESULTS: Sixty-five YAs with a range of tumour types participated. We identified seven themes and 13 subthemes. YAs found navigating the healthcare system difficult and commonly experienced prolonged diagnostic pathways. Participants felt under-informed about clinical details and the long-term implications of side-effects on daily life. YAs found online resources overwhelming but also a source of information and treatment support. Some patients regretted not discussing fertility before cancer treatment or felt uninformed or rushed when making fertility preservation decisions. A lack of age-tailored content or age-specific groups deterred YAs from accessing psychological support and rehabilitation services. CONCLUSIONS: YAs with cancer may miss some benefits provided to teenagers and young adults in age-tailored cancer services. Improving services for YAs in adult settings should focus on provision of age-specific information and access to existing relevant support.

OBJECTIVES To compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 (PDE5) inhibitor therapy. PATIENTS AND METHODS This was an open-label, crossover study of sildenafil and tadalafil (taken as needed). After a 4-week baseline assessment, 367 men with ED (mean age 54 years) were randomized to receive sildenafil for 12 weeks followed by tadalafil for 12 weeks or vice versa (8-week dose optimization and 4-week assessment phases). During dose optimization, patients started taking 25- or 50-mg sildenafil or 10-mg tadalafil and could titrate to find their optimum dose (25-, 50- or 100-mg sildenafil; 10- or 20-mg tadalafil). After completing both 12-week periods, patients chose which treatment to continue during an 8-week extension. Efficacy was measured with the International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) diary. RESULTS Of the 291 men who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose tadalafil (P < 0.001) for the 8-week extension. The IIEF erectile function domain scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient percentage success scores for SEP2 (penetration) were: baseline (46%), sildenafil (post-baseline 82%) and tadalafil (post-baseline 85%; P = 0.06, sildenafil vs tadalafil), and for SEP3 (successful intercourse) were: baseline (19%), sildenafil (post-baseline 72%), and tadalafil (post-baseline 77%; P = 0.003, sildenafil vs tadalafil). The only treatment-emergent adverse events that were reported by > 5% of men were headache and flushing. CONCLUSIONS In men with ED who were naive to PDE5 inhibitor therapy, sildenafil and tadalafil were both effective and well tolerated. After treatment with sildenafil and tadalafil, 29% of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8-week extension.

This commentary provides an overview of recent initiatives in Rhode Island to promote human papillomavirus (HPV) vac-30 cination with the goal of protecting Rhode Island adolescents against vaccine-preventable HPV-associated cancers. With the exception of the introduction of a recent school entry requirement, most of the initiatives and related activities described were conducted as part of a cooperative agreement between 35 RIDOH and CDC, and were supported by the Prevention and Public Health Fund.1

Objectives The aim of this study was to evaluate the long-term safety and durability of efficacy of tadalafil for pulmonary arterial hypertension. Background Tadalafil is an oral phosphodiesterase-5 inhibitor approved for PAH treatment. In the multicenter, placebo-controlled, randomized, 16-week PHIRST (Pulmonary Arterial Hypertension and Response to Tadalafil) study, tadalafil 40 mg improved exercise capacity and delayed clinical worsening. Methods Eligible patients from PHIRST received once-daily tadalafil 20 mg (T20 mg) or 40 mg (T40 mg) (n = 357) in the double-blind, 52-week, uncontrolled extension study (PHIRST-2); 293 patients completed PHIRST-2. Durability of efficacy was explored using the 6-min walk distance (6MWD) test. Clinical worsening and changes in World Health Organization functional class were evaluated. Results The safety profile of tadalafil in PHIRST-2 was similar to that in PHIRST, with typical phosphodiesterase-5 inhibitor adverse events. The 6MWDs achieved in PHIRST for the subset of patients receiving T20 mg and T40 mg in both PHIRST and PHIRST-2 (406 ± 67 m [n = 52] and 413 ± 81 m [n = 59] at PHIRST-2 enrollment, respectively) were maintained at PHIRST-2 completion (415 ± 80 m [n = 51] and 410 ± 78 m [n = 59], respectively). Numerically fewer patients who were on T40 mg in PHIRST and PHIRST-2 experienced World Health Organization functional class deterioration (6% [n = 5]) compared with those randomized to T20 mg (9% [n = 7]) across both studies. Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were associated with fewer clinical worsening events. Conclusions Long-term treatment with tadalafil was well tolerated in patients with pulmonary arterial hypertension. In patients receiving either T20 mg or T40 mg, the improvements in 6MWD demonstrated in the 16-week PHIRST study appeared sustained for up to 52 additional weeks of treatment in PHIRST-2. (Pulmonary Arterial Hypertension and Response to Tadalafil Study; NCT00549302 )

Objectives Financial stress has been identified as a barrier to antiretroviral adherence, but only in resource- limited settings. Almost half of HIV-infected Australian adults earn no regular income and, despite highly subsidised antiretroviral therapy and universal health care, 3% of HIV-infected Australians cease antiretroviral therapy each year. We studied the relationship between financial stress and treatment adherence in a resource-rich setting. Methods Out-patients attending the HIV clinic at St Vincent's Hospital between November 2010 and May 2011 were invited to complete an anonymous survey including questions relating to costs and adherence. Results Of 335 HIV-infected patients (95.8% male; mean age 52 years; hepatitis coinfection 9.2%), 65 patients (19.6%) stated that it was difficult or very difficult to meet pharmacy dispensing costs, 49 (14.6%) reported that they had delayed purchasing medication because of pharmacy costs, and 30 (9.0%) reported that they had ceased medication because of pharmacy costs. Of the 65 patients with difficulties meeting pharmacy costs, 19 (29.2%) had ceased medication vs. 11 (4.1%) of the remaining 270 patients (P

OBJECTIVES To determine if baseline characteristics, treatment efficacy, psychosocial outcomes or tolerability were associated with patient preference for sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS In an open-label, crossover study of sildenafil (25, 50 or 100 mg) and tadalafil (10 or 20 mg), dosed as needed, after a 4-week baseline assessment, 367 men with ED were randomly assigned to sildenafil followed by tadalafil or vice versa (8-week dose optimization and 4-week assessment phase for each treatment period). Patients completing both periods chose which treatment they preferred for an 8-week extension phase. Bivariate logistic regression and stepwise logistic regression were used to determine if any baseline characteristics or post-baseline measurements were associated with the patients’ treatment preference. Baseline variables examined were age, race, ED aetiology/duration, body mass index, smoking status, alcohol consumption, vital signs, comorbid medical conditions, and baseline scores for the International Index of Erectile Function (IIEF) domains, Psychological and Interpersonal Relationship Scales (PAIRS) domains, and Sexual Encounter Profile (SEP) diary questions. Post-baseline variables examined were therapy sequence, dosage, and differences in IIEF and PAIRS domains, SEP scores, in number/timing of sexual attempts and in the severity of side-effects (overall patient perception). RESULTS Of 291 patients completing both treatments and indicating a preference, 85 (29%) preferred sildenafil and 206 (71%) preferred tadalafil. Variables were individually analysed using bivariate analysis; one baseline characteristic (presence/absence of hyperlipidaemia) and 13 post-baseline measurements were significantly associated with the patients’ treatment preference. Variables were analysed as a group using stepwise logistic regression; a set of six post-baseline factors was identified as significantly associated with patient preference. Dosage choice, reductions in the PAIRS time concerns domain, IIEF intercourse satisfaction domain improvements, smaller side-effect severity scores, more sexual attempts, and increased SEP4 scores (satisfaction with erection hardness) during the tadalafil or sildenafil treatment periods were all significantly associated with preference for tadalafil or sildenafil. CONCLUSIONS We identified no baseline characteristics that prospectively distinguish patients who will prefer tadalafil or sildenafil. Patient differences in time concerns, dosage choice, intercourse satisfaction, treatment tolerability, number of sexual attempts and satisfaction with erection hardness were the set of factors most significantly associated with treatment preference, and the preference observed for tadalafil (71%) or sildenafil (29%) might be substantially accounted for by differences in these factors during the tadalafil and sildenafil treatment periods.

The aim of this study was to assess the effect of tadalafil (0.5, 2.5, and 10 mg/kg per day) on the progression of pulmonary arterial hypertension (PAH) in early treatment and on the survival rate in late treatment on the monocrotaline (MCT)-induced PAH rat model. Tadalafil was administered once daily to rats for 3 weeks from the day of MCT-injection or 21 days after the injection. With early treatment, tadalafil at 10 mg/kg per day prevented the development of PAH by maintaining mean pulmonary artery pressure within the normal range and attenuated right ventricular hypertrophy. With late treatment, tadalafil tended to increase the partial pressure of oxygen in arterial blood and dose-dependently improved the survival rate by 55%, 60%, and 70% at 0.5, 2.5, and 10 mg/kg per day, respectively, versus 40% in the MCT-control group. Both early and late treatments with tadalafil were associated with elevated lung cyclic guanosine monophosphate (cGMP). These results suggest that tadalafil relaxes pulmonary arteries by elevating cGMP in lungs and extend survival time by improving pulmonary hemodynamics even when treatment occurs in the late phase of PAH. Thus, it is expected that tadalafil may be an effective, once-daily treatment option in humans with PAH. Keywords:: tadalafil, phosphodiesterase 5 (PDE5) inhibitor, pulmonary artery hypertension (PAH), monocrotaline (MCT), survival

OBJECTIVE To assess the maintenance of efficacy of duloxetine beyond 3 months, using data from several long-term, open-label studies, as the efficacy of duloxetine 40-mg twice daily for treating women with stress urinary incontinence (SUI) for up to 3 months has been established in several randomized, placebo-controlled clinical trials. PATIENTS AND METHODS Data from 1424 patients (Cohort A) enrolled in three 12-week, placebo-controlled clinical trials and their uncontrolled, open-label extensions, and in one uncontrolled, open-label study, were used to assess long-term continuation rates and continued efficacy based on responses to the validated Patient Global Impression of Improvement (PGI-I) scale for up to 30 months. Data from another 2758 patients (Cohort B) enrolled in an additional placebo-controlled study and its open-label extension were used to assess PGI-I ratings, reductions in incontinence episode frequency (IEF) recorded on urinary diaries, and the relationship between PGI-I ratings and reductions in IEF for up to 72 weeks. RESULTS In Cohort A, the duloxetine continuation rate at 1 year was 42.5%. At 12, 24 and 30 months, most (83%, 83% and 88%, respectively) patients in Cohort A who continued treatment rated their incontinence in one of the three ‘better since starting treatment’ PGI-I categories. Both the median IEF reductions (50–77%) and the PGI-I ‘better’ ratings (70–88% of patients) remained fairly consistent over 72 weeks in Cohort B. Finally, IEF reductions increased with increasing PGI-I ratings (≈46% for ‘a little better’, 75% for ‘much better’ and 95% for ‘very much better’) over the first year of treatment. CONCLUSION The benefits of duloxetine were maintained in patients who continued treatment for up to 30 months. However, these favourable results need to be interpreted cautiously, as many patients discontinued treatment and those with better responses are more likely to continue taking medication.

Objective This observational study was conducted across Europe to assess health outcomes in men with erectile dysfunction (ED) who took tadalafil, sildenafil citrate (sildenafil), or vardenafil HCl (vardenafil) for 6 mo. Methods Therapy effectiveness and patient satisfaction were evaluated using established and new questions on erectile function. Behavioural, psychological, and relationship outcomes were assessed using the short form of the Psychological and Interpersonal Relationship Scales (SF-PAIRS). Results In nine European countries at 904 sites, 8047 patients were enrolled and 94% (7560) selected either tadalafil (5315), sildenafil (1252), or vardenafil (993) for treatment at baseline. Of the 7560, 3998 (52.9%) took the same drug for 6 mo. Baseline characteristics across the three treatment groups were comparable: mean age approximately 56 yr, moderate or severe ED, and mean International Index of Erectile Function-Erectile Function domain score about 13. Tadalafil, sildenafil, and vardenafil were therapeutically effective and improved patient satisfaction in the 40–58% of men who completed 6 mo of a single therapy. Patients taking tadalafil consistently had numerically higher levels of therapeutic effectiveness and satisfaction compared with patients who took sildenafil or vardenafil. The three cohorts had statistically significant changes from baseline in response to SF-PAIRS and there were significant differences, in favour of tadalafil, among cohorts in the Time Concerns domain. Conclusion In a large observational study that mimics a routine clinical setting, most patients selected an inhibitor of phosphodiesterase 5 to treat ED, which resulted in a high level of therapeutic effectiveness and patient satisfaction.

Factors that influence the number of sexual intercourse attempts among men with erectile dysfunction (ED) before initiation of ED treatment were investigated in a population of 4998 men enrolled in the (Erectile Dysfunctions) Observation Study (EDOS). Our results showed that increasing age, increasing severity and duration of ED, and decreasing satisfaction with one's sex life and partner were all associated with a reduced number of sexual intercourse attempts in the 4 weeks prior to enrollment in EDOS.

Introduction Although sildenafil citrate (sildenafil) and tadalafil are efficacious and well‐tolerated treatments for erectile dysfunction (ED), preference studies have shown that patients may favor one medication over the other. Aim To determine whether psychosocial outcomes differed when men with ED received tadalafil compared with sildenafil. Main Outcome Measures Measures included a treatment preference question, Psychological and Interpersonal Relationship Scales (PAIRS), and Drug Attribute Questionnaire. Methods Randomized, open‐label, crossover study. After a 4‐week baseline, men with ED (N = 367; mean age = 54 years; naive to type 5 phosphodiesterase inhibitor therapy) were randomized: tadalafil for 12 weeks then sildenafil for 12 weeks or vice versa (8‐week dose optimization/4‐week assessment phases). During dose optimization, patients started with 10 mg tadalafil, or 25 or 50 mg sildenafil and could titrate to their optimal dose (10 or 20 mg tadalafil; 25, 50, or 100 mg sildenafil). Medications were taken as needed. Patients completing both 12‐week periods chose which medication to continue during an 8‐week extension. Results Of 291 men completing both treatment periods, 71% (N = 206) chose tadalafil and 29% (N = 85) chose sildenafil ( P P P P Conclusions As measured with PAIRS, men with ED had higher sexual self‐confidence and spontaneity and less time concerns related to sexual encounters when treated with tadalafil compared with sildenafil. These psychosocial outcomes may help explain why more men (71%) preferred tadalafil for the treatment of ED in this clinical trial. Dean J, Hackett GI, Gentile V, Pirozzi‐Farina F, Rosen RC, Zhao Y, Warner MR, and Beardsworth A. Psychosocial outcomes and drug attributes affecting treatment choice in men receiving sildenafil citrate and tadalafil for the treatment of erectile dysfunction: Results of a multicenter, randomized, open‐label, crossover study. J Sex Med 2006;3:650–661.

To evaluate, in a randomized, double-blind, placebo-controlled, multicentre trial, the safety and efficacy of on-demand tadalafil (an oral phosphodiesterase type-5 inhibitor approved in many countries for treating erectile dysfunction, ED) in a Western European population of men with mild-to-severe ED.Patients were randomized according to baseline severity of ED in a ratio of 3 : 1 to receive either tadalafil 20 mg or placebo for 12 weeks. Primary efficacy endpoints were mean changes from baseline to endpoint (12 weeks) in the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and percentages of 'Yes' responses to Sexual Encounter Profile (SEP) diary Question 2 ('Were you able to insert your penis into your partner's vagina?') and Question 3 ('Did your erection last long enough for you to have successful intercourse?'). Secondary endpoints included mean changes from baseline to endpoint in IIEF Intercourse Satisfaction and Overall Satisfaction domains, selected questions of the IIEF, and the percentage of 'Yes' responses to Global Assessment Questions (GAQ) at the last visit. Other analyses included the percentage of patients in each treatment group at endpoint with IIEF EF domain scores in the normal range (26), the frequency of intercourse attempts and mean per-patient intercourse success rate at various times after dosing.The mean age of the patients was 53 years and 80% had a history of ED ofor = 1 year. The mean baseline EF domain score was 13.5, with 40.5% of patients in the severe category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4 for placebo (P0.001). In addition, 73.9% of sexual intercourse attempts were successful (SEP-Q3) in tadalafil-treated patients, compared with 29.9% in placebo-treated patients during the period after baseline (P0.001). Tadalafil significantly improved the mean IIEF intercourse satisfaction (5.1, tadalafil; 1.1, placebo) and overall satisfaction domain scores (3.9, tadalafil; 0.5, placebo), P0.001. GAQs used to assess the overall effect of the treatment indicated that tadalafil was superior to placebo (P0.001) in improving erections (82.1%, tadalafil; 23.1%, placebo) and sexual activity (78.6% and 17.3%). The most common treatment-emergent adverse events more frequent (2%) with tadalafil than placebo were headache, dyspepsia, flushing, back pain, pain in limb and myalgia. These adverse events were mostly mild to moderate.Tadalafil improved erectile function and was well tolerated when taken by men from Western Europe with mild-to-severe ED.

Background Tadalafil 40 mg orally once daily, was shown to be well-tolerated and efficacious for pulmonary arterial hypertension in a 16-week, double-blind, placebo (PBO)-controlled trial. Inclusion criteria included the option for background bosentan. Analyses of tadalafil in treatment-naive patients and as add-on to bosentan were pre-specified. Objectives were to provide safety and efficacy data for both groups. Methods Groups analyzed included: treatment-naive + PBO; treatment-naive + tadalafil; background bosentan + PBO; and background bosentan + tadalafil. Patients randomized to tadalafil or PBO ( N = 405) were analyzed by bosentan use (yes = 216, no=189). Treatment differences in 6-minute walk distance (6MWD, PBO-adjusted), functional class (FC), clinical worsening (CW) and adverse events were assessed. Hazard ratios (HRs) with 95% confidence intervals (CIs) are presented for FC and CW. Results At Week 16, PBO-adjusted 6MWD increases were 44 m (CI: 20 to 69 m; n = 37) for tadalafil 40 mg in treatment-naive patients and 23 m (CI: −2 to 48 m; n = 42) for tadalafil 40 mg add-on to bosentan. The 6MWD for treatment-naive and background bosentan PBO patients decreased by 3 m and increased by 19 m, respectively, at Week 16 compared with baseline. Two (5%) treatment-naive patients had CW with tadalafil 40 mg vs 8 (22%) with PBO (HR = 3.3, CI: 1.1 to 10.0). Two (5%) background bosentan patients had CW with tadalafil 40 mg add-on vs 5 (11%) for PBO add-on (HR = 1.9, CI: 0.4 to 10.2). Adverse events for tadalafil monotherapy and as add-on were similar. Conclusion Tadalafil 40 mg was well-tolerated and provided clinical benefit in patients as monotherapy. It was also well-tolerated when added to background bosentan, but data are insufficient to conclude additional benefit.

Steroids are widely dispersed throughout the biosphere where they fulfil a plethora of roles as bioregulators in both plants and animals. Indeed the simplest organism yet discovered to be utilizing them is a water mold which deploys a pheromone, oogoniol, which is a steroid. Within the animal kingdom, true hormonal use of the oestrogens appears to be restricted to the phyla Arthropoda and Chordata whereas their elaboration appears to have originated as early as ≈400 million years ago with the phyla Mollusca and Echinodermata which developed the cytochrome P450arom necessary to convert androstenedione to oestrone and testosterone to oestradiol. Until relatively recently it was assumed that, in the human, the endocrine oestrogens were largely if not exclusively involved in reproductive physiology. They were known to be responsible, with other agents, for the complex signalling and signal transduction which prepares the female organism for the key events of ovulation, blastocyst implantation, maternal adaptation to pregnancy and lactation—all of which, being central to the survival of the species, are highly conserved. However, the last half century has seen a major expansion in our understanding of the range of oestrogenic activity in physiology. The physico-chemical characteristics of the oestrogens and their receptors provide a signal and signal transduction system of high utility which has found a role in many systems unrelated to reproduction.

A pilot study of 107 women aged 60-69 years recently suggested that the measurement of broadband ultrasound attenuation (BUA) provides a superior cost effective pre-screen referral method for bone mineral density (BMD) measurement by DXA (dual-energy X-ray absorptiometry) than can be achieved by clinical criteria (CC). The aim of this study was to compare the accuracy and cost effectiveness of BUA and clinical criteria in a younger cohort. 599 women aged 50-54 years (52.18 \pm 1.35) had previously been measured by DXA at lumbar spine and right femoral neck, along with BUA measurement of the right calcaneus. Each subject had also completed an extensive clinical and social questionnaire to ascertain those who would have met one or more of the six general clinical criteria adopted by our Centre. Each subject was classified by DXA using the WHO criteria as normal, osteopenic or osteoporotic, defined at lumbar spine or femoral neck. Sensitivity, specificity and accuracy were calculated for BUA and the clinical criteria, noting that analysis was undertaken with and without the oestrogen deficiency clinical criterion (CC1)c "Any oestrogen deficient woman who would want to be treated or would want to continue treatment if found to be osteopenic or osteoporotic". The accuracy for identifying osteoporotic subjects was 72.8% for BUA (at the point of matched sensitivity and specificity, 75 dB MHz^{-1}), 30.7% for CC(1-6) and 64.3% for CC(2-6). When osteopenic subjects were incorporated, the accuracies were 63.8% for BUA (at the point of matched sensitivity and specificity, 82 dB MHz^{-1}), 60.3% for CC(1-6) and 55.7% for CC(2-6). The minimum cost per osteoporotic subject correctly identified was £573.50 by DXA alone, £325 by BUA, £458 by CC(1-6) and £416 by CC(2-6). When osteopenic subjects were incorporated, the costs were £87, £83.50, £78 and £74, respectively. The overall cost, dependent upon the prevalence of osteoporosis (or osteopenia) within the population, more accurately indicates the feasibility of a population-based screening programme. For the identification of either osteoporotic or osteopenic subjects from the general population by DXA, the prevalence-compensated cost (cost per subject correctly identified multiplied by prevalence) is £45, irrespective of age cohort. If CC(2-6) were adopted for the identification of osteoporotic subjects alone, the prevalence-compensated cost would be £32 and £42 for the 50-54 and 60-69 aged cohorts, respectively. For BUA, the prevalence-compensated cost falls to £25 and £43 for the 50-54 and 60-69 aged cohorts, respectively. If osteoporotic or osteopenic subjects were to be identified in the 50-54 aged cohort, both CC(2-6) (£38) and BUA (£43) perform similarly to DXA alone. BUA appears to provide a valuable population pre-screen for the identification of osteoporotic subjects, less so for osteopenic. It is suggested that if both osteopenic and osteoporotic women are to be identified for clinical management incorporating DXA, then neither BUA nor clinical criteria are satisfactory referral methods. An unanswered question from this study, however, is whether ultrasound has an independent role in the assessment of fracture risk for perimenopausal women who do not have the benefit of referral for DXA.

Oestrogen has a wide variety of roles beyond its involvement in the control and modulation of human fertility. The relative oestrogen deficiency experienced by women following the menopause leads to a wide range of symptoms and conditions, from the vasomotor effects of the climacteric to an increased risk of cardiovascular disease, bladder dysfunction, osteoporosis, and possibly Alzheimer's disease. Most of these can be improved or at least modified by hormone replacement therapy (HRT). Unfortunately, acceptance of HRT is poor, mainly due to the return to cyclic or unscheduled bleeding and the fear of breast cancer. Selective oestrogen receptor modulators (SERMs) are thus being developed with the goal of eliminating these unwanted effects on breast and endometrium, while maintaining the benefits to the skeletal and cardiovascular systems. Raloxifene has received approval in the USA for osteoporosis prevention and others, such as Idoxifene and Droloxifene, are now in clinical trial. Unfortunately, they are not effective at treating the peri-menopausal vasomotor symptoms, and their effect on the central nervous system remains as yet unknown. However, Raloxifene is a major step towards the ideal goal of full receptor engagement in the non-reproductive tissues with concomitant nonengagement of the reproductive sites.

Public health initiatives aimed at changing the nation's diet rely on simple messages to persuade people to eat more from certain food groups and less from others. The underlying rationale of this strategy is that control is located firmly in the hands of the individual who can ‘choose’ health by following the guidelines. The research reported in this article found high levels of public awareness of nutritional guidelines, and a sense of personal control over health. However, accounts of other health-related agendas showed that being in control may mean choosing to become fitter or slimmer. Within these pursuits, nutritional concerns were prioritized only in so far as they were seen to serve the attainament of a desired body shape. Health professionals need to be aware that nutritional guidelines may be competing with other mediating factors along the chosen route to health.

Memory for pairs of unfamiliar children's faces was investigated in 29 children and adolescents suffering from left (LTLE) or right (RTLE) temporal-lobe epilepsy, before and after temporal-lobe surgery. Both immediate and delayed memory were tested. Before surgery, RTLE subjects performed worse than either LTLE subjects or normal children. After surgery, RTLE subjects improved significantly. Overall (after surgery), there was no significant LTLE-RTLE difference, but on delayed memory, the RTLE group was worse than the LTLE group. The results suggest specialization for facial memory in the right hemisphere of young patients, as in adults, despite early brain damage.

A well-conducted study initiation is critical to conducting clinical research trials in compliance with protocols and FDA regulations. This article will review those areas of a study initiation which can greatly impact compliance, offering tools that have proven useful in reducing protocol deviations and gaining better patient compliance.

To explore treatment patterns and resource utilization and cost for subjects with pulmonary arterial hypertension (PAH).Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization.In the final sample of PAH patients treated with bosentan (n=251) or sildenafil (n=455), average age was 57 years, 86% of patients were commercially insured, and 52% of patients were male. Gender distribution varied significantly across subgroups, with a lower proportion of males in the bosentan (30%) subgroup compared with the sildenafil group (64%) (p0.001). Average baseline Charlson comorbidity score was 2.4. Average numbers of fills per month were 0.8 and 0.4 for bosentan and sildenafil patients, respectively (p0.001). Over 80% of patients received only one PAH treatment in the first 90 days following the index date, with 28% of bosentan and 13% of sildenafil patients receiving combination therapy (p0.001). Over one-third of bosentan patients and one-quarter of sildenafil patients experienced a dose increase in the follow-up period (p=0.009). Sixteen percent of sildenafil patients experienced a dose decrease in the follow-up period, while a smaller proportion of patients receiving bosentan (4%) experienced a dose decrease (p0.001). On average, number of PAH-related per subject per month (PSPM) inpatient stays and emergency department visits and PSPM length of inpatient stays were statistically similar between the subgroups. PAH-related PSPM healthcare costs were high for both subgroups, with average monthly costs of $5,332 and $3,632 among bosentan and sildenafil patients, respectively (p=0.003). Differences in total costs were driven mainly by differences in pharmacy expenditures.Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, such as the potential for coding errors and lack of information on whether a drug was taken as prescribed. Furthermore, PAH severity (WHO functional class) was not assessed.

To evaluate short- and long-term safety and efficacy of duloxetine in women with predominant stress urinary incontinence (SUI).The study was a 6-week, double-blind, randomised, parallel, placebo-controlled study followed by an uncontrolled open-label extension (OLE) run in 342 study centres in 16 European countries. Women with predominant SUI were randomly assigned to placebo (n = 1380) or duloxetine 40 mg twice daily (n = 1378) for 6 weeks. Completers of the acute phase were enrolled in the OLE, which had a minimum duration of 6 weeks and ended, based on the approval status of duloxetine in the participating country.The primary outcome measure was the change in incontinence episode frequency (IEF) over 6 weeks. Secondary outcome measures were the long-term maintenance of effect on IEF and Patient Global Impression of Improvement (PGI-I), the short- and long-term impact on quality of life using the King's Health Questionnaire (KHQ), and the long-term safety of duloxetine.After 6 weeks, the decrease in weekly IEF was significantly greater with duloxetine treatment compared to placebo (-50.0 vs. -29.9%; p0.001). The percentage of responders (defined asor =50% decrease in IEF) was significantly higher with duloxetine treatment than with placebo (50.6 vs. 31.2%; p0.001). Duloxetine treatment was associated with improvements in weekly pad use (-31.4%), PGI-I ratings (63.6%), and KHQ score (-6.25) compared to placebo (-12.5%, 48.5% and -3.13, respectively, all p0.001). Treatment-emergent adverse events were significantly more common during duloxetine treatment (48.3%) than placebo (33.3%), (p0.001). Of the 2290 patients continuing into the OLE, 1165 (42.2%) completed the available duration, and 592 (21.5%) discontinued because of an adverse event (percentages relative to total randomised patients). Long-term efficacy in the OLE was assessed over a 72-week period and was maintained over that time. However, the results should be interpreted within the context that better responding patients are more likely to remain on duloxetine, while patients responding poorly are more likely to discontinue over time.Duloxetine seems to be an efficacious treatment with an acceptable safety profile for women with SUI. Achieved improvement is maintained over the longer term in those women who remain on therapy.

Pulmonary arterial hypertension (PAH) is a rare, progressive lung disorder that impairs performance of daily activities and quality of life (QoL), leading to right heart failure and death. Treatment options include prostanoids, endothelin antagonists, and phosphodiesterase type 5 inhibitors (e.g., tadalafil). Currently there is no cure for PAH, but tadalafil has improved exercise capacity in these patients.To explore the effect of tadalafil on health-related quality of life (HRQoL) measures.The Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) clinical trial examined the efficacy and tolerability of tadalafil for the treatment of PAH. The impact of tadalafil on HRQoL and exercise capacity, as measured by 6-minute walk test (6MW test), was also examined. Change from baseline to last non-missing post-baseline was examined for the SF-36, EQ-5D, and 6MW test, along with the relationship between HRQoL and 6MW test performance.Tadalafil 40 mg showed significant improvement over placebo for six of eight SF-36 domains, and EQ-5D index scores. Also, the tadalafil 40-mg group showed significant improvement over placebo on the 6MW test (p0.001), but no clear relationship was found between 6MW test performance and HRQoL.Results suggest that tadalafil 40 mg may significantly improve HRQoL and exercise capacity for PAH patients. Limitations of this study include its relatively short nature limited to 16 weeks and the relative heterogeneity of the study population.

OBJECTIVE: The objective of this review was to determine, from a systematic assessment of published data, the cost effectiveness of the neuraminidase inhibitor antiviral medication oseltamivir in comparison with usual care (i.e. over-the-counter medication such as analgesics and antipyretics for symptomatic relief) for the treatment of influenza. How the findings of each of the studies considered related to the methods used for each analysis and the assumptions made were specifically reviewed.RESULTS: The online search found 80 individual articles, 66 of which did not meet the pre-defined screening criteria. The 14 studies remaining reported cost, cost-effectiveness and cost-utility analyses for oseltamivir treatment in various groups: healthy adults and adolescents, children, elderly, and individuals at increased risk.CONCLUSION: Despite the range of values assumed for key probabilities such as the diagnostic certainty of influenza among people presenting with influenza-like illness, and how much work time is lost due to illness in healthy adults, base-case analyses consistently showed oseltamivir treatment to be cost effective or even cost saving for the four population groups studied, a conclusion that is in-line with previous reviews on this topic. However, clarity was frequently lacking in the published data in terms of various model assumptions and results, particularly with regards to the exact distributions of the constituting elements of savings and of quality-adjusted life years gained.

Background— Treatment options for pulmonary arterial hypertension target the prostacyclin, endothelin, or nitric oxide pathways. Tadalafil, a phosphodiesterase type-5 inhibitor, increases cGMP, the final mediator in the nitric oxide pathway. Methods and Results— In this 16-week, double-blind, placebo-controlled study, 405 patients with pulmonary arterial hypertension (idiopathic or associated), either treatment-naive or on background therapy with the endothelin receptor antagonist bosentan, were randomized to placebo or tadalafil 2.5, 10, 20, or 40 mg orally once daily. The primary end point was the change from baseline to week 16 in the distance walked in 6 minutes. Changes in World Health Organization functional class, clinical worsening, and health-related quality of life were also assessed. Patients completing the 16-week study could enter a long-term extension study. Tadalafil increased the distance walked in 6 minutes in a dose-dependent manner; only the 40-mg dose met the prespecified level of statistical significance ( P P =0.041), incidence of clinical worsening (68% relative risk reduction; P =0.038), and health-related quality of life. The changes in World Health Organization functional class were not statistically significant. The most common treatment-related adverse events reported with tadalafil were headache, myalgia, and flushing. Conclusions— In patients with pulmonary arterial hypertension, tadalafil 40 mg was well tolerated and improved exercise capacity and quality of life measures and reduced clinical worsening.

Seasonal influenza is a prevalent and highly contagious acute respiratory disease that, year on year, results in increased morbidity and mortality on a global scale. Because of the widespread and debilitating nature of the disease, annual influenza epidemics result in substantial workplace absenteeism, and the associated cost of lost productivity is a significant component of the substantial financial burden of the disease to society. The objective of this review was to identify studies that had attempted to quantify the impact of influenza upon otherwise healthy adults in terms of working days lost associated with an episode of influenza.Studies were included if they reported estimates of working days lost due to clinical, physician and/or self-diagnosis in adult patients or their dependants, or where this figure could be estimated from the data. Searches were conducted in MEDLINE, EMBASE, BIOSIS and the Cochrane Collaboration for articles published since 1995 in English, French or German. Of the 289 papers identified in the search, 28 (9.7%) met the inclusion criteria. The studies, involving study sites in North America, Western Europe, Asia and Australia, were categorized into three groups: (i) those reporting influenza diagnoses confirmed by laboratory testing, i.e. studies where influenza was the unambiguous cause of the working days lost (n = 7 studies reported in ten publications); (ii) those where influenza was confirmed by a physician without an accompanying laboratory test (n = 4 studies); and (iii) those where influenza was self-reported by study participants (n = 14 studies). Qualitative reporting of results was performed because of the large degree of heterogeneity observed between studies, potentially complicating the interpretation of any meta-analysis.The results from studies involving a laboratory-confirmed influenza diagnosis suggested that the mean number of working days lost ranged between 1.5 and 4.9 days per episode. Those papers that detailed working days lost per episode following physician diagnosis of influenza reported a range of 3.7-5.9 days per episode. Finally, estimates from papers reporting working days lost per episode of self-reported influenza ranged from1 day to 4.3 days per episode.Influenza imposes a significant burden on society, and this review highlights the significant economic impact it causes, i.e. the loss of productivity caused by both absenteeism and by staff functioning at reduced capacity even after they have returned to work. A number of prophylaxis and treatment options exist for influenza and should be given serious consideration in an attempt to reduce the economic burden on society.

In two recent case-control studies premature greying of the hair was associated with a lowering of bone mineral density (BMD) and osteopenia, suggesting that this might be a clinically useful risk marker for osteoporosis. We report a further re-examination of this proposal in 52 prematurely grey-haired women from East Yorkshire who responded to an advertisement inviting them for bone densitometry. Thirty-five had no clinical or drug history that could influence bone density. All were Caucasian with a mean age of 52.8 years. In the group as a whole the mean BMD values at the lumbar spine and femoral neck were no different from those of a young adult, but there was a trend toward a greater than average BMD than that of the local age-matched population (p = 0.097 and 0.218, respectively). Twenty women were premenopausal, with an average age of 45.3 years. Mean BMD values at the lumbar spine and femoral neck in this group were no different from those of young adults. There was, however, a trend toward a BMD greater than that of the local age-matched population at the femoral neck (p = 0.117). Fifteen women were postmenopausal with an average age of 62.9 years and an average age at menopause of 51.1 years. Mean BMD values at both the lumbar spine and femoral neck in this group were lower than those of young adults, but no different from those of the local age-matched population. In conclusion, our group of prematurely grey-haired women had average BMD for their age, and we are therefore unable to support the proposed clinical usefulness of premature greying as a risk marker for osteoporosis.

A prospective study of 199 patients over a two year period, 1 Jun 90 to 31 May 92 at the Louise Margaret Maternity Wing, Cambridge Military Hospital, Aldershot was undertaken to audit the uptake of an offer of conservative management of prolonged pregnancy to women at 42 weeks gestation. The labour outcomes of patients opting for conservative or induction management plans were recorded and the increased workload introduced to the Ultrasound Unit measured. Of the 91/199 (45.7%) patients who chose to be managed conservatively, 20 (22.0%) developed an abnormal result of a test of fetal surveillance, 16 (17.6%) were electively delivered because of an abnormal result. There were no significant differences in labour performance or neonatal outcome between those women opting for conservative management or induction of labour. 201 new ultrasound scans were booked, 129 were performed (0.4 scans/week/1000 deliveries).

This study has shown that surgery for hypertelorism or vertical orbital dystopia gives very satisfying results overall to the patients and their families and leads to a modest but highly significant objective improvement in appearance after surgery, as perceived by panels of laymen or hospital staff not known to the patients. The complexities of the methodology of panel assessments of appearance are discussed. The results of this study confirm the need to go beyond our traditional methods of assessing surgical outcome simply within our specialty.

Two intermolecular cross-linking amino acids, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), are promising markers in urine of collagen resorption because their levels in urine should reflect only collagen resorption and, unlike hydroxyproline, should not be influenced by degradation of either newly synthesized collagen molecules or noncollagenous proteins. Changes with age in the urinary excretion of HP and LP were studied in 24 h collections of urine from a group of 22 male and 27 female healthy subjects aged from 2 to 70 years. The pyridinolines were quantitated, utilizing their natural fluorescence, after resolution by reversed-phase HPLC. Levels of both pyridinolines were higher in children than in adults, but in adults no evidence of age or sex variations were observed except in the 20-30 year age group. Mean values of HP/Cr and LP/Cr in 37 adults (21-70 years) were 27.2 +/- 1.9 and 8.8 +/- 0.8 mumols/mol, respectively; in the 12 children (2-15 years) the mean values were 14.4 and 12.4 times higher than the respective adult values. Making certain assumptions, the mean amount of bone resorbed in normal adults was tentatively estimated at 1.9 g per 24 h. The finding that differences between children and adults in these relatively specific markers were greater than with hydroxyproline suggests that hydroxyproline values may considerably underestimate the actual amount of bone turnover occurring in growing children or overestimate the adult turnover rate.

The effect of warming glucose-free 0.5% bupivacaine to 37°C before injection for spinal anesthesia was studied in 20 patients having total knee replacement. Twenty additional patients having spinal anesthesia for the same procedure were given glucose-free 0.5% bupivacaine at room temperature (approximately 20°C). Onset, maximum cephalad spread, quality of sensory anesthesia, and duration and degree of motor blockade were the same in both groups. However, the duration of sensory anesthesia was significantly prolonged in patients who received bupivacaine at 37°C. The mechanism by which warming bupivacaine prolongs the duration of sensory spinal anesthesia is uncertain. However, a decrease in the dissociation constant (pKa) of bupivacaine owing to increasing the temperature to 37°C may account for some of this effect.

For many diabetics in end-stage renal failure, the initial therapy they receive will be continuous ambulatory peritoneal dialysis (CAPD) together with i.p. insulin. To date, all published protocols rely on empirical dosages based upon predialysis insulin requirements. A practical regimen for the institution of i.p. insulin administration during CAPD is described. The only endpoints used to determine insulin dosage were fasting plasma glucose 5 to 10 mmol/L and 2 h postprandial plasma glucose 8 to 15 mmol/L. An initial protocol related to body weight, dextrose content, volume, and timing of dialysate was based on a retrospective analysis of the results in our first 10 patients. Subsequently, a prospective assessment in an additional 22 patients confirmed the effectiveness of the regimen. The following protocol is recommended for the institution of i.p. insulin therapy in patients undergoing CAPD: Preprandial exchanges 1.36% dextrose-0.175 U/L dialysate/kg body weight 3.86% dextrose-0.25 U/L/kg Overnight exchanges 1.36% dextrose-0.1 U/L/kg 3.86% dextrose-0.15 U/L/kg Further adjustment of insulin dosage is then made on the basis of four hourly plasma glucose profiles. Self-monitoring of capillary blood glucose is recommended.

Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.

Early outcome results for 10 cases of modified hemispherectomy are presented. All patients had a history of infantile hemiplegia and intractable epilepsy. Pre- and postoperative measures for seizures and motor and cognitive and behavioural functioning are described. Early results are encouraging with no mortality and a low rate of complications. There was a complete cessation of seizures in seven patients and a considerable reduction in seizure frequency in two. Motor functioning was largely unaffected. Behaviour problems tended to improve at the cessation of seizures. IQ scores did not deteriorate as a consequence of operation and some patients showed considerable gains in IQ with the passage of time. Details of cognitive functioning are described.

During puberty the effects of adrenal androgens upon skeletal maturation are obscured by the influence of gonadal steroids. Suppression of gonadarche with an analogue of luteinizing hormone releasing hormone (LHRHa) affords an opportunity to examine the onset and progression of adrenarche in the absence of pubertal levels of gonadal steroids in a controlled fashion and to explore the relationship between adrenal androgens and the rate of epiphyseal maturation. In 29 children with central precocious puberty, gonadarche was suppressed with LHRHa administration for 1-4 yr. During LHRHa exposure, dehydroepiandrosterone sulfate (DHAS) levels, as an index of adrenal maturation, were constant or increased in an age-expected manner. The change in bone age for change in chronologic age decreased from 1.7 +/- 0.1 to 0.49 +/- 0.05 (P = 0.00005), indicating that the LHRHa-induced return to a prepubertal gonadal steroid environment was associated with a slowing of skeletal maturation. DHAS levels were correlated with the rate of skeletal advancement before (r = 0.57, P = 0.001) and during 12 to 48 mo of exposure to LHRHa (r = 0.52, P = 0.003). A negative correlation of DHAS values with subsequent increases in predicted mature height was observed (r = -0.49, P = 0.007). Thus, in children with central precocious puberty, adrenarche progressed normally during LHRHa suppression of gonadarche. In children with the onset of progression of adrenarche during maintenance of a prepubertal gonadal steroid milieu, there was less evidence than in preadrenarchal children of a restraint upon skeletal maturation. These data suggest that adrenal androgens contribute importantly to epiphyseal advancement during childhood.

Serum fructosamines and glycosylated haemoglobin have been examined in groups of patients with (n = 27) and without (n = 39) diabetes mellitus and chronic renal failure, or undergoing renal replacement therapy. Elevated values of fructosamines were found in nondiabetic haemodialysis patients as compared to the other non-diabetic patients. The relationship between fructosamines and glycosylated haemoglobin appeared to be attenuated by uraemia. Successful pancreatic transplantation returned fructosamine and glycosylated haemoglobin values to normal.

The gonadotropin-releasing hormone-like agonist D-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. Since accelerated statural growth and bone maturation are clinical features of precocity not well controlled by conventional therapies, we examined the effects of prolonged LHRHa therapy for 18 consecutive months on growth and skeletal maturation in nine girls with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin pulsations and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- S.E.M.) of 9.35 +/- 0.64 cm per year during the 19 months before treatment to 4.58 +/- 0.60 cm per year during treatment (P less than 0.001). Bone age advanced a mean of 9.4 +/- 2.3 months during treatment. These changes resulted in a mean increase of 3.3 cm in predicted height (P less than 0.01). Complete suppression of the pituitary-gonadal axis can be maintained by LHRHa therapy, resulting in slowing of excessively rapid growth and skeletal maturation and in increased predicted adult height in girls with precocious puberty.

We have investigated the effect of the administration of small doses of intraperitoneal insulin (mean 2.7 ± 1.45 u/L) on the hyperlipidemia associated with continuous ambulatory peritoneal dialysis (CAPD) in nine non-diabetic patients. Despite significant lowering of both fasting (6.21 ± 0.9 → 4.2 ± 0.5 mmoI/L) and postprandial (9.74 ± 1.1 → 7.4 ± 1.06 mmol/L) blood glucose levels, we saw no effect on serum total cholesterol, triglycerides or B lipoproteins.

During puberty the effect of adrenal androgens on skeletal maturation and growth is obscured by the influence of gonadal steroids. Suppression of gonadarche with an LHRHa affords an opportunity to explore the association between adrenarche, skeletal development and adult stature. In 16 girls with central precocious puberty (CPP), gonadarche was suppressed by LHRHa administration for 12 to 36 months. During treatment dehydroepiandrosterone sulfate (DS) levels, an index of adrenarche, were constant or increased in an age expected fashion. Rate of bone maturation (ΔBA) for change in chronologic advancement (ΔCA) decreased as shown by ΔBA/ΔCA < 1 in all subjects. DS levels were positively correlated with ΔBA/ΔCA (R = 0.07, p < 0.002). Statural growth also decreased but less than bone maturation so that predicted mature height (Bayley and Pinneau) was increased in all but one subject. A significant negative linear regression of DS levels with increase in predicted height was observed (R = 0.70, P < 0.003). Conclusions: 1) In girls with CPP, adrenarche progressed during LHRHa suppression of gonadarche. 2) In preadrenarchal girls, LHRHa administration was associated with a more striking slowing of bone maturation with relatively lesser effects on height velocity. In those girls with the onset or progression of adrenarche in the absence of gonadal steroids, therapy was associated with less evidence of restraint on bone maturation. 3) These data are compatible with a direct effect of adrenal androgens upon skeletal maturation and growth.