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This paper investigates least squares spectral analysis as a tool to analyze non-stationary signals from pass-by noise measurements in water. The spectral analysis involves successive least squares fitting of a finite Fourier series to approximate the observation in a piecewise manner. The least squares spectral analysis is used to search the signals for first- and second-order periodicity as well as the presence of fundamental periodicity. A first-order analysis reveals line components in the signals, whereas a second-order analysis reveals periodic amplitude modulations. Analysis with a higher-order finite Fourier series reveals harmonic structures in the signals. The main contribution of this paper is the model of a magnitude-squared cosine wave which can be used to analyze second-order periodicity. The developed short-time least squares spectral analysis is illustrated on noise radiated from a rigid inflatable boat in shallow water.

Background/Aims: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. Methods: Race/ethnicity-based expected frequencies of height 2 test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). Results: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (–2.97 vs. –2.56 SD) and to their mid-parental heights (–2.47 vs. –1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (–0.86 vs. –0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (–1.12 vs. –0.08 SD). Male predominance did not differ by race for any or all indications. Conclusion: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.

SummaryContext Girls with Turner Syndrome (TS) treated or not treated with growth hormone (GH) are prone to overweight. Therefore, we hypothesize that puberty induction in TS is associated with weight gain. Methods We analyzed weight changes (BMI-SDS) between onset of GH treatment and near adult height (NAH) in 887 girls with TS enrolled in KIGS (Pfizer International Growth Database). Puberty was induced with estrogens in 646 (72·8%) girls with TS. Results Weight status did not change significantly between GH treatment start and 1 year later (mean difference −0·02 BMI-SDS), but increased significantly (P < 0·001) until NAH (+0·40 BMI-SDS). The BMI-SDS increased +0·21 until start of puberty (P < 0·001). Girls with spontaneous and induced puberty showed similar BMI-SDS changes. Puberty induction at ≥12 years was associated with a significant (P < 0·001) less increase of BMI-SDS (+0·7 BMI-SDS) between baseline and NAH compared to puberty induction at

Objectives The aim of this randomized controlled study was to evaluate the long term effectiveness of a reduced shrinkage stress resin composite in Class II restorations. The material was compared intra-individually with a microhybrid resin composite. Materials and methods Each of 50 patients with at least one pair of two similar sized Class II cavities participated (22 female, 28 male, mean age 43 years, range 18–64). Each participant received in each pair, in a randomized way, one Class II restoration performed with a reduced shrinkage stress resin composite (InTen-S) and the other restoration with a microhybrid resin composite restoration (Point 4). Both restorations were placed with an etch-and-rinse bonding system and an oblique layering technique. A total of 106 restorations, 33 premolar and 73 molars, were placed. The restorations were evaluated blindly each year using modified USPHS criteria. The overall performance of the experimental restorations was tested after intra-individual comparison using the Friedmans two-way analysis of variance test. The hypothesis was rejected at the 5% level. Results At 15 years, 91 restorations were evaluated. The drop out frequency was 15 restorations (5 male, 3 female participants; 2 premolar and 13 molar restorations). Except for 2 participants, who reported slight symptoms during a few weeks after placement, no post-operative sensitivity was observed at the recalls. The overall success rate at 15 years was 77%. Twenty-one non acceptable restorations were observed during the 15 years follow up, 10 InTen-S (21.7%) and 11 Point 4 (24.4%) restorations (p > 0.05). Annual failure rates for the resin composites were 1.5% and 1.6%, respectively. The main reasons for failure were secondary caries (8) and resin composite fracture (7). The differences between premolar vs. molar restorations and between restorations in male vs. female participants were not significant. Significant differences were observed between 2-surface vs. 3-surface restorations. Significance During the 15-year follow up, the reduced shrinkage stress resin composite showed a good clinical durability in Class II cavities, but not significantly better than the control microhybrid resin composite. Secondary caries and material fracture were the main reasons of failure.

Aim: The aim of this study was to evaluate the response to recombinant growth hormone (GH) treatment in short children with CHARGE syndrome. Patients: We identified 51 children (28 boys and 23 girls) in KIGS (Pfizer International Growth Database). The median chronological age was 7.6 years at the start of GH therapy and 13.2 years at the latest visit. Evaluation for GH deficiency (n = 33) was based on the following: peak GH level 7.3 μg/l and IGF-I level -2.01 standard deviation score (SDS). Sixteen subjects (9 boys) were followed longitudinally for 2 years. Results: Birth length (median SDS, -0.47) and weight (-0.97) were slightly reduced. At the start of GH therapy, height was -3.6 SDS, BMI -0.7 SDS, and the GH dose was 0.26 mg/kg/week. At the latest visit after 2.7 years of GH therapy, height had increased to -2.2 SDS and BMI to -0.5 SDS. In the longitudinal group, height increased from -3.72 SDS at the start of GH therapy to -2.92 SDS after 1 year to -2.37 SDS after 2 years of therapy (start - 2 years: p < 0.05), height velocity increased from -1.69 to 2.98 to 0.95 SDS, and BMI and GH dose (mg/kg/week) remained almost unchanged. Conclusions: Our data show a positive effect of conventional doses of GH on short-term growth velocity for the longitudinal as well as for the total group, without any safety issues.

Background: Children receiving stimulants for attention deficit hyperactivity disorder (ADHD) frequently present to pediatric endocrinology clinics for evaluation and treatment of growth disorders. The worldwide prevalence of stimulant use in children with ADHD also receiving recombinant human growth hormone (rhGH) and the impact on response to rhGH are unknown. Methods: Data on children enrolled in the KIGS® (Pfizer International Growth Study) registry were evaluated for the associated diagnosis of ADHD prior to initiation of Genotropin® rhGH. Concomitant stimulant medications and auxological information were captured. Response to rhGH was evaluated using established growth prediction models. Results: The prevalence of ADHD in KIGS was 2.3% (1,748/75,251), with stimulants used in 1.8% (1,326/75,251). Children with idiopathic growth hormone deficiency (IGHD) who received stimulants grew significantly less (1.1 cm) in the first year of rhGH therapy than expected for rhGH-treated non-ADHD IGHD children. After one year of rhGH, idiopathic short stature (ISS) children with ADHD were significantly shorter [0.74 cm (with stimulants) and 0.69 cm (without stimulants)] than non-ADHD ISS children. Conclusions: We demonstrated an impaired response to rhGH in IGHD and ISS children with ADHD. Our findings suggest that the ADHD phenotype, alone or in conjunction with stimulant therapy, may impair the short-term growth response to rhGH.

Background Response to growth hormone (GH) therapy may vary between individual patients. Therefore the use of GH in children should be closely monitored to avoid over, under, or ineffective treatment regimens. The treatment response can be evaluated using growth prediction models. In an effort to improve the accuracy of these prediction models, Ranke et al. (J Clin Endocrinol Metab 95(3):1229–37) proposed a novel ‘data-driven’ approach based on a quantitative analysis of a large cohort of patients from the Pfizer International Growth Database (KIGS) treated with Genotropin (human growth hormone). This model allows physicians to predict and evaluate the level of growth response and responsiveness for their patients so they can adapt treatment accordingly. By comparing the actually observed and the predicted growth response the ability of an individual to respond to GH (responsiveness) can be estimated and further treatment can be adapted accordingly Objective To determine the potential population level reduction in the amount of GH used and impact on height outcome of using this data-driven approach to guide treatment decisions, compared to conventional, ‘experience-based’ GH treatment in prepubertal patients with growth hormone deficiency (GHD) or Turner syndrome (TS). Methods A model was developed to study the height outcome and the total amount of GH used in the presence or absence of data-driven treatment decisions. The proportion of patients for whom height outcome could be improved or GH use could be reduced (i.e. for low compliance, high or low responder) was estimated using the KIGS cohort. The analysis assumed that this segmentation allows physicians to tailor dosage to the individual patient’s needs or even to discontinue therapy when it is not effective. The analysis used a 4-year time horizon, with Germany as an example country, but results are extendable to other countries. Only the total amount of GH used was included, and effects were defined as the height outcome after 4 years. Results The analysis estimated that an evidence-driven approach may reduce the total amount of GH utilized by 7.0 % over 4 years for the treatment of short stature in prepubertal patients with GHD and TS in Germany. Despite the reduction in drug use the average growth outcomes remained unaffected with the new treatment approach. Univariate and probabilistic sensitivity analyses showed that the results are robust. Conclusions Our analysis showed that using a data-driven approach to guide treatment decisions for children with GHD or TS is estimated to result in efficiencies in the amount of GH used, without reducing the average growth in the population.

Treatment with growth hormone (GH) has become standard practice for replacement in GH-deficient children or pharmacotherapy in a variety of disorders with short stature. However, even today, the reported adult heights achieved often remain below the normal range. In addition, the treatment is expensive and may be associated with long-term risks. Thus, a discussion of the factors relevant for achieving an optimal individual outcome in terms of growth, costs, and risks is required. In the present review, the heterogenous approaches of treatment with GH are discussed, considering the parameters available for an evaluation of the short- and long-term outcomes at different stages of treatment. This discourse introduces the potential of the newly emerging prediction algorithms in comparison to other more conventional approaches for the planning and evaluation of the response to GH. In rare disorders such as those with short stature, treatment decisions cannot easily be deduced from personal experience. An interactive approach utilizing the derived experience from large cohorts for the evaluation of the individual patient and the required decision-making may facilitate the use of GH. Such an approach should also lead to avoiding unnecessary long-term treatment in unresponsive individuals.

Background/Aims: The study aim was to develop and validate models for long-term prediction of growth in prepubertal children with idiopathic growth hormone deficiency (GHD) or Turner syndrome (TS) for optimal, cost-effective growth hormone (GH) therapy. Methods: Height was predicted by sequential application of annual prediction algorithms for height velocity in cohorts of GHD (n = 664) and TS (n = 607) as documented within KIGS (Pfizer International Growth Database). As height prediction models also require an estimate of weight, new algorithms for weight increase during the first to fourth prepubertal years on GH were developed. Results: When height was predicted from the start of GH treatment, the predicted and observed mean (SD) gain over 4 years was 30.4 (3.4) cm and 30.1 (4.9) cm, respectively, in GHD patients, and 27.2 (2.2) cm and 26.6 (3.5) cm, respectively, in TS patients. For all 4 years, gains of weight SD scores (SDS) were accurately described as a function of weight SDS and observed gain in height SDS (R2 > 0.89). Conclusion: In GHD and TS patients treated with GH, an accurate prepubertal long-term prediction of height development in groups is possible. Based on this, an optimal individual height outcome could be simulated.

Background/Aims: The aim was to describe the factors determining total pubertal growth (TPG) in adolescents with growth hormone deficiency (GHD), Turner syndrome (TS), who were small for gestational age (SGA) or had idiopathic short stature (ISS). Methods: The patients were documented within KIGS (Pfizer International Growth Database). TPG was defined as growth from puberty onset – spontaneous (>B1 or testes >3 ml) or induced with sex steroids to adult height in idiopathic GHD (n = 639; males 399), TS (n = 463), SGA (n = 59; males 35), and ISS (n = 130; males 87). Algorithms to predict TPG at puberty onset were developed by multiple linear regression analysis. Results: In GHD (males, females) and TS TPG could be explained with the same four predictors: (1) age (years) at puberty onset (neg.), (2) age – bone age at puberty onset (pos.), (3) height – midparental height (SDS) at puberty onset (neg.), and (4) mean dose of growth hormone (GH) during puberty (pos.). The algorithms explained 66, 65 and 68%, respectively, of the variability with total errors of 4.5, 3.8 and 2.9 cm, in spontaneous and induced TPG. Conclusions: TPG is determined by the same factors at puberty onset in adolescents with GHD, TS, SGA or ISS treated with GH. Thus, TPG depends mostly on the outcomes achieved at the end of prepubertal growth and less so on the dose of GH.

Background: Growth hormone (GH) therapy successfully increases height prognosis in children with GH deficiency (GHD); however, adult height data are still limited. Aim: This study investigated near-adult height (NAH) in patients with idiopathic GHD (i.e. those with a GH peak Methods: All patients were registered in the Pfizer International Growth Study Database (KIGS). Median (10th to 90th percentile) values are given and measurements were expressed as standard deviation scores (SDS). Parental-adjusted height was determined. Results: GH therapy was started at a median age of 9.2 (range 4.9–12) years in patients with isolated GHD (n = 1,619, 60% males) and at 7.7 (range 2.8–12.2) years in those with MPHD (n = 554, 65% males; p < 0.001) at a median dose of 0.20 mg/kg/week. Height SDS at onset of therapy was –3.1 (range –4.5 to –2.1) and –3.8 (range –5.7 to –2.3), respectively (p < 0.001). The maximum GH peak and insulin-like growth factor I SDS were significantly (p < 0.05) lower in patients with MPHD than in those with isolated GHD. Both groups showed a significant (p < 0.05) increase in height SDS at 1 year that continued until the onset of puberty. Parental-adjusted height at the start of puberty was –0.1 (range –1.6 to 1.1) in patients with isolated GHD and –0.4 (range –1.9 to 1.2) in those with MPHD. Parental-adjusted NAH SDS in patients with isolated GHD was 0.0 (range –1.5 to 1.2) and slightly, but significantly, higher than NAH (–0.3, range –2.1 to 1.2; p < 0.001) in patients with MPHD. In patients with isolated GHD, total change in height SDS while receiving GH therapy was 1.6 (range 0.5–3.2), and the change in height SDS at puberty was 0.1 (range –0.7 to 1). The respective values were 2.6 (range 0.9–4.6) and 0.2 (range –1 to 1.3) in patients with MPHD. Parental-adjusted NAH was slightly lower in girls than in boys with isolated GHD, but no gender difference was observed in patients with MPHD. Multivariate analysis in patients with GHD and MPHD showed that higher birth weight, taller parents, greater height at onset, first-year responsiveness, and predicted height velocity were the most important predictors of NAH. Conclusions: 89% of patients with isolated GHD and 81% of those with MPHD reached an NAH within their genetic potential while receiving GH therapy. Most of the height gain occurred during prepubertal years.

Information about the expected growth response of children to GH therapy is currently inadequate.The aim of the study was to compare observed and expected growth in response to GH in prepubertal children and to propose how these parameters can be used to optimize GH therapy. Indices considered were observed growth, observed growth relative to reference data [height sd score (Ht SDS), change in (Delta) Ht SDS, height velocity (HV)], and observed growth relative to growth predicted from prediction models [Studentized residual (SR)]. Design/Setting/Patients/Intervention: Growth data from KIGS-Pfizer International Growth Database-on prepubertal children aged 1-13 yr with severe GH deficiency (GHD; maxGH5 microg/liter; n = 2129), with less-severe GHD (maxGH of 5-10 microg/liter; n = 3075), and with Turner syndrome (n = 2350), and short children born small for gestational age (n = 993) were analyzed before and during 2 yr of GH treatment.For each patient group, growth responses during the first 2 yr of GH treatment were established. The relationships of HV and DeltaHt SDS with SR were determined.Reference data were generated for assessing adequate individual responses. Responses to GH in terms of HV and DeltaHt SDS were greatest in children with severe GHD. HV and DeltaHt SDS were highly correlated with SR during only the first year of GH treatment (R approximately 0.7; P0.001).Decisions on GH therapy regimens should be made using both traditional (HV or DeltaHt SDS) and prediction model-derived (SR) indices of growth response.

Background/Aims: There is limited information about adult height (AH) outcomes and the factors influencing outcomes of growth hormone (GH) therapy in short children born small for gestational age (SGA). Methods: AH (SDS) and Δheight (SDS) from GH start to AH were analyzed in 161 SGA children who had reached AH (55 with Silver-Russell syndrome, SRS). Results: SGA patients treated to AH were started on GH (median) 0.25 mg/kg/week at an age of 7.8 years with a height of –3.8 SDS. AH after 7.7 years was –2.2 SDS and –1.1 SDS below mid-parental height (MPH). AH (SDS) was explained by: height (SDS) at GH start (+), Δheight (SDS) 1st year on GH (+), years on GH (+), maternal height (SDS) (+), length (SDS) at birth (+), and the diagnosis of SRS (–) (explained variability 70%; error 0.6 SD). Gain in height (SDS) was explained by: Δheight (SDS) 1st year on GH (+), years on GH (+), height – MPH (SDS) at GH start (–) (explained variability 60%; error 0.7 SD). Conclusions: Algorithms for AH outcomes provides useful information about the potential of long-term growth on GH in short children born SGA.

Aim: To assess final height in children with growth hormone deficiency (GHD) treated with human recombinant growth hormone (GH). Methods: Final height data for 401 Swedish children with idiopathic GHD and treated with GH, included in KIGS (Pfizer International Growth Database) between 1987 and spring 2006, were analysed retrospectively. Data were grouped according to sex, age and severity of GHD. Height at entry into KIGS, at the onset of puberty and near final height were analysed between groups. Results: Groups were heterogeneous for GHD, which ranged from partial to severe. For all groups, mean final height corrected for mid-parental height was within the normal Swedish height range. In patients with severe GHD, mean final height was almost identical to mean normal Swedish height. About 16% of patients showed disproportionality (short legs) at final height and were significantly shorter than other patients. The parents of these children also demonstrated short stature. Conclusion: Children with idiopathic GHD receiving GH replacement therapy can achieve a final height that as a group is within the normal range and all achieve a height within their genetic potential.

Context: GH therapy is an accepted measure to increase adult height in young prepubertal patients suffering from growth failure related to chronic kidney disease (CKD). The impact of GH therapy on final height (FH) in CKD patients of pubertal age is unclear.Objective: This study set out to analyze near-FH in a cohort of GH-treated CKD patients.Design, Settings, and Patients: Of 240 evaluable patients in the Pfizer International Growth Database (KIGS) with CKD, 39% were prepubertal and 61% were pubertal at baseline; 45% were on conservative treatment for CKD, 28% were on dialysis, and 27% were in the period after renal transplantation.Main Outcome Measures: Near-FH, relation to pubertal stage, and factors predictive of growth response were the main outcome measures.Results: Mean height sd scores increased continuously during GH treatment until near-FH by 1.2 and 1.6 in boys and girls, respectively. Mean near-FH differed significantly from prepubertal patients showing severely delayed puberty (−3.6), late pubertal patients (−2.9), early pubertal patients (−2.2), and prepubertal patients with normal onset of puberty (−2.0). The initial degree of stunting, degree of bone age retardation, duration of GH therapy, time spent on conservative treatment/dialysis, pubertal delay (>2 sd), gender, and age at start of GH treatment were significant predictors of growth response to GH therapy, explaining between 33 and 61% of the overall variability.Conclusions: Long-term GH therapy of CKD patients in prepubertal and pubertal age results in an increased adult height, but response is diminished in patients on dialysis and/or with severely delayed puberty.

The aim of this study was to evaluate in an intraindividual comparison the durability of a polyacid-modified resin composite/resin composite open sandwich restoration in a 9 years follow-up. A polyacid-modified resin composite (PMRC; compomer, Dyract) was placed as an intermediate layer and covered with resin composite (RC, Prisma TPH). A direct RC restoration was used as control.Each of 57 patients, received at least one pair of Class II restorations, one open sandwich and one resin composite control. In total 75 pairs of Class II restorations, 68 premolars and 82 molars, all in occlusion, were placed by two dentists. Most of the cavities were surrounded by enamel. The restorations were evaluated at baseline, 6, 12, 24, 36 months and 9 years by slightly modified USPHS criteria. Survival of restorations grouped on the two different techniques was determined using Kaplan-Meier survival curves.After 9 years, 14 of 135 evaluated restorations were estimated as unacceptable, 6 in the sandwich group and 8 in the control group. Over all annual failure rate during the 9-year period was 1.1%. The survival rate was not significant different between the two techniques (p=0.604). Reasons of failure were: secondary caries (8), fracture of tooth (1), fracture of restoration (2), endodontic treatment (3).Both restorative techniques showed good durability during the 9-year period. No clinical advantage was observed for the sandwich technique.

The aim of this study was to evaluate in vivo the interfacial adaptation of class II resin composite restorations with and without a flowable liner. In 24 premolars scheduled to be extracted after 1 month, 48 box-shaped, enamel-bordered class II cavities were prepared and restored with a flowable liner (FRC, Tetric Flow/Tetric Ceram/Syntac Single-Component) or without (TRC), cured with three different curing modes: soft start and 500- or 700-mW/cm2 continuous irradiation. Interfacial adaptation was evaluated by quantitative scanning electron microscopic analysis using replica method. Gap-free adaptation in the cervical enamel (CE) was observed for FRC and TRC in 96.2 and 90.2%, for the dentin (D) in 63.6 and 64.9%, and for occlusal enamel (OE) in 99.7 and 99.5%, respectively. The difference between the two restorations was not statistically significant (ns). Significant better adaptation was observed for OE than CE and D (p

The introduction of the 2 neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has offered new options for the prevention and treatment of influenza. This article summarizes a Swedish consensus guidance document on the rational use of antiviral drugs in the management of influenza virus infections. Vaccination remains the cornerstone for influenza prophylaxis. Target groups for the annual vaccination programme are the 'at-risk' individuals, i.e. elderly patients ( > or = 65 y) and patients with chronic pulmonary disease or cardiovascular disease or other chronic diseases predisposing for a complicated course of influenza. Antiviral drugs are not a substitute for influenza vaccination, but could be used as adjuncts. Currently, 3 drugs have been approved for the treatment of influenza, including zanamivir and oseltamivir and the M2 inhibitor amantadin. Amantadin has come to very limited use, has recently been withdrawn from the Swedish market and is available only on a named patient basis. Compared with amantadin, the NAIs have clear advantages because of their broader anti-influenza activity against both type A and B, improved safety profiles and low potential for inducing drug resistance. The NAls are therefore recommended as first options in the treatment of influenza. Oseltamivir can be taken orally, whereas zanamivir is for oral inhalation. Limited in vitro and in vivo data suggest that oseltamivir is less potent against influenza B, whereas zanamivir seems equally effective against influenza A and B. In influenza-positive healthy adults and children, treated within 48 h after symptom onset, the NAIs shorten the duration of illness by about 1 d. No significant effect on the duration of symptoms has been documented in treated at-risk patients with influenza. Owing to their limited therapeutic benefit, general use of the NAIs in the treatment of influenza is not recommended, but they can be advocated on an individualized basis for patients with severe influenza who can start therapy within 48 h of the onset of symptoms. Zanamivir is the preferred choice in a confirmed influenza B epidemic. For prevention of influenza, 2 drugs are approved, oseltamivir in adults above 12 y old and amantadin in people above 10 y old. The 70-90% protective efficacy of oseltamivir for household postexposure prophylaxis and for seasonal prophylaxis is comparable to that reported for amantadin. Oseltamivir is the preferred drug for prophylactic use. Chemoprophylaxis is targeted at high-risk groups and should be considered on a case-by-case basis depending on the circumstances and the population requiring protection. A broader preventive use of oseltamivir can be advocated in at-risk groups during seasons when there is a poor antigenic match between the epidemic strains and the vaccine strains. Oseltamivir prophylaxis is otherwise recommended for patients unable to be vaccinated and for families exposed to influenza which include a member of the at-risk groups. In high-risk hospital units and in institutions caring for the elderly, oseltamivir prophylaxis, in combination with vaccination, can be recommended as measures to control an influenza outbreak.

Recombinant human (rh) growth hormone (GH) raises the glomerular filtration rate (GFR) in healthy individuals. Concern has been raised that long-term rhGH treatment in short children with chronic kidney disease (CKD) may accelerate the progression of CKD via induction of glomerular hyperfiltration. We compared the decline in GFR in children with CKD enrolled in two large clinical studies with (KIGS registry) and without (ESCAPE trial) concomitant rhGH treatment and followed for up to 10 years. Estimated GFR (eGFR) was determined at yearly intervals. The annual decline in eGFR was analyzed cross-sectionally for up to 10 years and longitudinally for 5 years. In the KIGS registry 367 patients with CKD stages II–IV (mean age 8.0 years; 72 % boys; mean eGFR 38.4 ml/min/1.73 m2) were treated with 0.33 mg rhGH/kg per week for at least 1 year. In the ESCAPE trial 274 non-rhGH-treated patients with CKD stages II–IV (mean age 11.6 years; 61 % boys; mean GFR 47.3 ml/min/1.73 m2) were followed for at least 1 year. At the 5-year follow-up, the mean loss of eGFR in the KIGS children receiving continuous rhGH treatment (n = 97) did not differ significantly from that in the controls (n = 113) in the ESCAPE trial (−5.8 vs. −8.6 ml/5 years, respectively; p = 0.17). Absolute height and eGFR at baseline were significant correlates of the annual eGFR loss (model R 2 =0.121). Long-term rhGH-treatment does not accelerate the decline in GFR in short children with CKD. Height and baseline eGFR are significant predictors of the loss of GFR in CKD patients.

Many children with idiopathic short stature (ISS) remain short as adults. Height can be improved permanently by growth hormone (GH) treatment, as in children with Turner syndrome or born small for gestational age. Although GH treatment for ISS is an approved indication in the United States, there is ongoing controversy in Europe about approving GH treatment for this indication as well as determining the optimal mode of treatment. In addition to data from randomized controlled trials, data from pharmacoepidemiological surveys such as the Pfizer International Growth Study Database (KIGS) have provided substantial information about the short-term and long-term effects of GH on growth and adult height in children with ISS. Based on published articles and a recent survey from KIGS on 454 patients who have reached adult height, we attempted to categorize those children with ISS who have the greatest chances of achieving a normal adult height, or at least gain the most height following GH treatment. This analysis provides a rational basis for discussion about the most efficacious and cost-effective uses of GH treatment in children with ISS.

Vaccination of children - summary and conclusions from a systematic reviewThe full review can be found in Acta Paediatrica 2010; 99: s461

It has become common practice to apply GH treatment in short Turner syndrome patients with the objective of promoting growth. The variability in response and the high costs of this treatment demand the individualization and optimization of therapy. Based on 686 prepubertal Turner patients from the Kabi International Growth Study (KIGS; Pharmacia & Upjohn, Inc. International Growth Database), we undertook a multiple regression analysis of height velocity (centimeters per yr) by using various parameters of potential relevance. Derived prediction models for the first 4 yr of GH treatment were validated with 76 additional KIGS patients and 81 patients from Tuebingen, Germany. Among the 6 predictors identified, the most influential variable for first year growth response was the natural log (ln) of the weekly GH dose. The first year growth response was also correlated with age and distance between height and target height (SD score; both negative) and body weight SD, number of GH injections per week, and oxandrolone treatment given additionally (positive). The first year model explains 46% of the variability, with 1 SD of 1.26 cm. For the second to fourth years, 5 predictors were identified: height velocity during previous years, weekly GH dose (ln), weight SD, oxandrolone therapy (all positive), and age (negative). These models explained 32%, 29%, and 30% of the variability, respectively, with SD scores of 1.1, 1.0, and 1.0 cm, respectively. When the models were applied to the other cohorts, no significant difference was noted between observed and predicted responses. Although the parameters used in our models do not entirely explain the variability in the growth response in Turner syndrome, the parameters themselves were clinically relevant to our present understanding and proved to be of high precision. Some of the tested markers, such as karyotype, do not contribute to the growth response. These variables make the models practical and suitable for planning beneficial and cost-effective therapy.

A mathematical model for predicting the growth response in patients with Turner syndrome who received growth hormone (GH) therapy was developed by analysing data from KIGS, the Pharmacia & Upjohn International Growth Database. A model for year 1 of GH therapy explained 46% of the variability of the growth response, with GH dose being the most important of the predictors of height velocity. In years 2-4 of therapy, height velocity during the previous year was the most important predictor, suggesting that an individual's initial response to GH may determine the height outcome of treatment. Additional predictors of height velocity in years 1-4 of GH therapy included age (negative), weight SDS and additional treatment with oxandrolone. The predictions in all 4 years were highly accurate, as indicated by the low error SDs. However, relatively low predictive power (R) during years 2-4 of treatment suggests the models are missing other parameters that would explain more of the variability of the growth response. These growth prediction models could help clinicians to design individualized treatment regimens, provide realistic expectations of therapy outcomes, and adjust treatment on the basis of detected differences between observed and predicted height velocities.

A total of 195 children (117 males and 78 females) with idiopathic growth hormone deficiency (IGHD), treated with growth hormone (GH) for at least 1 year before puberty onset and who had completed tre

GEA 857 [2-(4-chlorophenyl)-1,1-dimethylethyl 2-amino-3-methylbutanoate], a structural analogue of the 5-HT uptake blocker alaproclate, was tested for its ability to modify tremor and salivation induced by muscarinic agonists (oxotremorine, arecoline) and acetylcholinesterase inhibitors (physostigmine, THA) in the male rat. These agents were employed at submaximal doses. GEA 857, similarly to alaproclate (Ogren et al. 1985a & b), produced a dose-dependent, statistically significant (in the 5-20 mg/kg dose range) enhancement of the tremor response induced by all four cholinergic stimulants. However, unlike alaproclate, GEA 857 failed to enhance salivation in a consistent manner. GEA 857 itself did not produce tremor in the absence of the muscarinic agonists or the acetylcholinesterase inhibitors. The potentiation of oxotremorine tremor by GEA 857 could be fully blocked by atropine (1 mg/kg intraperitoneally). Unlike alaproclate, GEA 857 failed to affect 5-HT uptake or 5-HT metabolism in the 10-20 mg/kg dose range. However, similarly to the action of alaproclate, the potentiating effect of GEA 857 on muscarinic responses could be explained neither by actions on serotonergic mechanisms nor by actions on muscarinic receptor mechanisms in the striatum. Evidence is presented suggesting that the ability of GEA 857 to enhance responses evoked by muscarinic agonists involves inhibitory properties of GEA 857 at certain membranal Ca2+-dependent K+ channels, the blockade of which can potentiate or prolong muscarinic cholinergic actions.

To study the durability of a recently developed low-shrinkage resin composite, suggested to counter the stress formation in direct resin composite restorations.Each of 50 patients received one or two pair(s) of Class II restorations. The first restoration in the pair was a low-shrinkage resin composite (InTen-S) and the second a hybrid resin composite restoration (Point 4). Both restorations were placed with an etch-and-rinse bonding system and an oblique layering technique. A total of 106 restorations, 33 premolar and 73 molars, were placed. The restorations were evaluated annually.At 5 years, 97 restorations were evaluated. Two participants reported slight postoperative sensitivity symptoms for a few weeks after placement. Twelve non acceptable restorations were observed during the 5 years, five InTen-S (10.4%) and 7 Point 4 (14.3%) (not significant). Secondary caries was the main reason for failure (8) followed by composite fracture (2) and tooth fracture (2).The low-shrinkage resin composite showed good durability, but not significantly better than the control resin composite in Class II cavities. Most failures occurred at the last part of the study. Secondary caries was the main reason for failure.

The degree of conversion (DC), of a universal hybrid resin composite cured with LED curing units with low and high power densities and a 510 mW/cm2 quartz tungsten halogen unit, was investigated with Fourier Transform Raman spectroscopy. Three curing depths (0, 2, 4mm) and 0 and 7 mm light guide tip - resin composite (LT - RC) distances were tested. The DC of the LED units varied between 52.3% - 59.8% at the top surface and 46.4% - 57.0% at 4 mm depth. The DC of specimen cured with a 0 mm LT- RC distance at 4 mm depth varied between 50.8% - 57.0% and with 7 mm distance between 46.4% - 55.4%. The low power density LED unit showed a significantly lower DC for both distances at all depth levels compared to the other curing units (p0.05). Significant differences between the other curing units were only found at the 4 mm depth level cured from 7 mm distance (p0.05). The reduction in DC by increasing LT- RC distance was less than 10% for all curing units. It can be concluded that the improved LED curing units could cure the studied resin composite to the same DC as the control unit.

To evaluate the durability of a new open sandwich restoration with, as shown in a previous scanning electron microscope study, improved interfacial adaptation. A polyacid-modified resin-based composite (PMRC; compomer) was placed as an intermediate layer and covered with resin composite (RC). A direct RC restoration was used as control.Of 57 patients, each received at least one pair of Class II restorations, one PMRC/RC open sandwich and one RC control. In total, 75 pairs of Class II restorations, 68 premolars and 82 molars, all in occlusion, were placed by two dentists. Most of the cavities were surrounded by enamel. The restorations were evaluated at baseline, 6, 12, 24 and 36 months by a slightly modified USPHS criteria.Five of 148 restorations evaluated during 3 years were rated as unacceptable. Two, one in each group, because of endodontic treatment and one RC restoration was replaced because of tooth fracture. Secondary caries was observed contiguous to one restoration in each group at the 36-month recall. Except for the two patients with pulpitis, none of the others reported postoperative sensitivity. No significant differences were seen between the restoration techniques. For marginal adaptation a significant change occurred between baseline and 6 months in both groups. For marginal discoloration, a significant change was observed at 6 months in the sandwich group and at 36 months in the RC group. Color match of the resin composite material changed significantly in both groups at 36 months. It was concluded that both techniques showed good durability during the 3-year follow up.

Background Mathematical models can be developed to predict growth in short children treated with growth hormone (GH). These models can serve to optimize and individualize treatment in terms of height outcomes and costs. The aims of this study were to compile existing prediction models for short children born SGA (SGA), to develop new models and to validate the algorithms. Methods Existing models to predict height velocity (HV) for the first two and the fourth prepubertal years and during total pubertal growth (TPG) on GH were applied to SGA children from the KIGS (Pfizer International Growth Database) - 1st year: N = 2340; 2nd year: N = 1358; 4th year: N = 182; TPG: N = 59. A new prediction model was developed for the 3rd prepubertal year based upon 317 children by means of the all-possible regression approach, using Mallow's C(p) criterion. Results The comparison between the observed and predicted height velocity showed no significant difference when the existing prediction models were applied to new cohorts. A model for predicting HV during the 3rd year explained 33% of the variability with an error SD of 1.0 cm/year. The predictors were (in order of importance): HV previous year; chronological age; weight SDS; mid-parent height SDS and GH dose. Conclusions Models to predict growth to GH from prepubertal years to adult height are available for short children born SGA. The models utilize easily accessible predictors and are accurate. The overall explained variability in SGA is relatively low, due to the heterogeneity of the disorder. The models can be used to provide patients with a realistic expectation of treatment, and may help to identify compliance problems or other underlying causes of treatment failure.