Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions

Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.     

PK/PD modeling of aminoglycoside nephrotoxicity

Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.     

Aminoglycoside nephrotoxicity: modeling,simulation, and control

The main constraints on the administration of aminoglycosides are the risks of nephrotoxicity and ototoxicity, which can lead to acute, renal, vestibular, and auditory toxicities. In the present study we focused on nephrotoxicity. No reliable predictor of nephrotoxicity has been found to date. We have developed a deterministic model which describes the pharmacokinetic behavior of aminoglycosides (with a two-compartment model), the kinetics of aminoglycoside accumulation in the renal cortex, the effects of aminoglycosides on renal cells, the resulting effects on renal function by tubuloglomerular feedback, and the resulting effects on serum creatinine concentrations. The pharmacokinetic parameter values were estimated by use of the NPEM program. The estimated pharmacodynamic parameter values were obtained after minimization of the least-squares objective function between the measured and the calculated serum creatinine concentrations. A simulation program assessed the influences of the dosage regimens on the occurrence of nephrotoxicity. We have also demonstrated the relevancy of modeling of the circadian rhythm of the renal function. We have shown the ability of the model to fit with 49 observed serum creatinine concentrations for a group of eight patients treated for endocarditis by comparison with 49 calculated serum creatinine concentrations (r(2) = 0.988; P < 0.001). We have found that for the same daily dose, the nephrotoxicity observed with a thrice-daily administration schedule appears more rapidly, induces a greater decrease in renal function, and is more prolonged than those that occur with less frequent administration schedules (for example, once-daily administration). Moreover, for once-daily administration, we have demonstrated that the time of day of administration can influence the incidence of aminoglycoside nephrotoxicity. The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1:30 p.m. Clinical application of this model might make it possible to adjust aminoglycoside dosage regimens by taking into account both the efficacies and toxicities of the drugs.     

Effects of Repetitive Loading on Bone Mass and Geometry in Young Male Tennis Players: A Quantitative Study Using MRI

Pre‐ and early puberty seem to be the most opportune times for exercise to improve bone strength in girls, but few studies have addressed this issue in boys. This study investigated the site‐, surface‐, and maturity‐specific exercise‐induced changes in bone mass and geometry in young boys. The osteogenic effects of loading were analyzed by comparing the playing and nonplaying humeri of 43 male pre‐, peri‐, and postpubertal competitive tennis players 10–19 yr of age. Total bone area, medullary area, and cortical area were determined at the mid (40–50%) and distal humerus (60–70%) of both arms using MRI. Humeral bone mass (BMC) was derived from a whole body DXA scan. In prepubertal boys, BMC was 17% greater in the playing compared with nonplaying arm (p < 0.001), which was accompanied by a 12–21% greater cortical area, because of greater periosteal expansion than medullary expansion at the midhumerus and periosteal expansion associated with medullary contraction at the distal humerus. Compared with prepuberty, the side‐to‐side differences in BMC (27%) and cortical area (20–33%) were greater in peripuberty (p < 0.01). No differences were found between peri‐ and postpuberty despite longer playing history in the postpubertal players. The osteogenic response to loading was greater in peri‐ compared with prepubertal boys, which is in contrast with our previous findings in girls and may be caused by differences in training history. This suggests that the window of opportunity to improve bone mass and size through exercise may be longer in boys than in girls.     

Correlations between Beck's suicidal ideation scale, suicidal risk assessment scale RSD and Hamilton's depression rating scale

INTRODUCTION: Most of the people who will attempt suicide, talk about it beforehand. Therefore, recognition of suicidal risk is not absolutely impossible. Beck's suicidal ideation scale and Ducher's suicidal risk assessment scale (RSD) are common tools to help practicians in this way. AIM OF THE STUDY: These scales and the Hamilton's depression scale were included in an international multicentric, phase IV, double-blind study, according to two parallel groups who had been administered a fixed dose of fluvoxamin or fluoxetin for six weeks. This allowed examination of the correlations between these scales and the relations, which could possibly exist between suicidal risk, depression and anxiety. RESULTS: (a) Relationships between the Beck's suicidal ideation scale, the suicidal risk assessment scale RSD and Hamilton's depression before treatment. Before treatment, the analysis was conducted with 108 male and female depressive outpatients, aged 18 or over. Results revealed a significant positive correlation (with a Pearson's correlation coefficient r equal to 0.69 and risk p<0.0001) between Beck's suicidal ideation scale and the suicidal risk assessment scale RSD. These scales correlate less consistently with Hamilton's depression (Beck/Hamilton's depression: r=0.34; p=0.0004-RSD/Hamilton's depression: r=0.35; p=0.0002). We observed that the clinical anxiety scale by Snaith is also strongly correlated to these two suicidal risk assessment scales (Beck/CAS: r=0.48; p<0.0001-RSD/CAS: r=0.35; p=0.0005). Besides, the item "suicide" of Hamilton's depression scale accounts for more than a third of the variability of Beck's suicidal ideation scale and the suicidal risk assessment scale RSD. According to these results, the suicidal risk evaluated by these two scales seems to be significantly correlated with anxiety as much as with depression. On the other hand, the Clinical Global Impression is fairly significantly correlated with Beck's suicidal ideation scale (r=0.22; p=0.02), unlike the suicidal risk assessment scale RSD (r=0.42; p<0.0001) and Hamilton's depression scale (r=0.58; p<0.0001); (b) Relationships between Beck's suicidal ideation scale, the suicidal risk assessment scale RSD and Hamilton's depression under treatment. The follow-up under treatment (fluvoxamin or fluoxetin) during six weeks revealed the significantly better sensitivity of the RSD in comparison with Beck's suicidal ideation scale and Hamilton's depression scale, showing the significantly faster improvement in the RSD (p<0.0001). There was no significant difference between the evolution of Beck's suicidal ideation scale and Hamilton's depression scale. So, under treatment with fluvoxamin or fluoxetin, the improvement in suicidal risk appears to be as rapid as the improvement in depression. If we look at the treatment prescribed, only the suicidal risk assessment scale RSD revealed a significant difference between the two molecules, with more rapid improvement with fluvoxamin (p=0.015) from D14. CONCLUSION: In conclusion, the results of this study hypothesize that the suicidal risk, as assessed by Beck's suicidal ideation scale and the suicidal risk assessment scale RSD, appears to be consistently correlated with both the level of anxiety and depression. The study also suggests that all antidepressants may not be equally effective on suicidal risk.     

Mechanical loading with or without weight-bearing activity: influence on bone strength index in elite female adolescent athletes engaged in water polo, gymnastics, and track-and-field

Bone health is considered not to benefit from water-based sports because of their weight-supported nature, but available evidence primarily relies on DXA technology. Our purpose was to investigate musculoskeletal health in the upper and lower body in well-trained adolescent female athletes using pQCT and compare these athletes with less-active, age- and sex-matched peers. Bone mineral content, volumetric cortical and trabecular BMD, total and cortical area, and bone strength index were assessed at the distal and proximal tibia and radius in four groups of adolescent females (mean age, 14.9?years) including water polo players (n?=?30), gymnasts (n?=?25), track-and-field athletes (n?=?34), and nonactive controls (n?=?28). Water polo players did not show any benefit in bone strength index or muscle size in the lower leg when compared with controls. In contrast, gymnasts showed 60.1?% and 53.4?% greater bone strength index at the distal and proximal tibia, respectively, than nonactive females (p?相似文献