| 1. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 2. |
- Das, Anirban, et al.
(författare)
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Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium.
- 2023
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Ingår i: Cancer discovery. - 2159-8290.
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Tidskriftsartikel (refereegranskat)abstract
- Immune-checkpoint inhibition (ICI) is effective for replication-repair deficient, high-grade gliomas (RRD-HGG). Clinical/biologic impact of immune-directed approaches after failing ICI-monotherapy are unknown. We performed an international study on 75 patients treated with anti-PD1; 20 are progression-free (median follow-up: 3.7-years). After 2nd-progression/recurrence (n=55), continuing ICI-based salvage prolonged survival to 11.6-months (n=38; p<0.001), particularly for those with extreme mutation burden (p=0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and immune-microenvironment. Response to re-irradiation was explained by an absence of deleterious post-radiation indel signatures (ID8). Increased CTLA4-expression over time, and subsequent CTLA4-inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to reinvigoration of peripheral immune and radiological responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/ synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology.
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| 3. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Growth hormone dose-dependent pubertal growth : a randomized trial in short children with low growth hormone secretion
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:3, s. 158-170
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency.Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height.Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS.Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.
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| 4. |
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| 5. |
- Chaplin, John, 1955, et al.
(författare)
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Improvements in Behaviour and Self-Esteem following Growth Hormone Treatment in Short Prepubertal Children
- 2011
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 75:4, s. 291-303
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children. Methods: 99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3-11 years, randomized to fixed or individual GH doses and their parents completed questionnaires (Child Behaviour Checklist, Birleson Depression Self-Report Scale, Abbreviated Parent-Teacher Questionnaire, I Think I Am, Well-Being Visual-Analogue Scales for Short-Stature Children) at baseline (BL) and after 3, 12, and 24 months. Results: At BL, children showed higher levels of internalizing behaviour (p < 0.001), lower levels of externalizing behaviour (p < 0.006) and self-esteem (p < 0.001) compared to reference values. During GH treatment, behavioural measures (p < 0.001) and depression (p < 0.01) changed towards the mean of the population within the first 3 months and remained improved to 24 months. Self-esteem improved at all time points (p < 0.001), and in all subgroups, as did well-being dimensions stability and mood (p < 0.05). Multiple regression analysis showed that greater improvements were related to lower BL value, height gain, higher maximal GH value, being older, and being male. Conclusion: On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment.
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| 6. |
- Chaplin, John, 1955, et al.
(författare)
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When Do Short Children Realize They Are Short? : Prepubertal Short Children's Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment
- 2012
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 77:4, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. Methods: Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children's and parents' responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. Results: Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother's height, parental sense of the child's tallness and age explained more variance in children's sense of tallness (34%) than measured height (0%). Conclusion: Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.
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| 7. |
- Holmgren, Anton, et al.
(författare)
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Detailed analyzes of the relation between childhood BMIand gain in height during puberty, separated into different Components
- 2016
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Ingår i: International Journal of Obesity. - 0307-0565 .- 1476-5497.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: We have previously found that childhood BMI is inversely related to pubertal height gain: overweight/obese children of both genders have less specific pubertal height gain. The QEPS-model (describing total growth in height as a combination of four mathematical functions), can be used for calculation of estimates of pubertal growth. Growth in height during puberty can be described as a combination of continuous ongoing growth, Q(ES), and a specific pubertal growth function, P. Objectives: To investigate the importance of when overweight/obesity starts during childhood in relation to subsequent growth in height during puberty; and to study the relationship between childhood BMI and pubertal growth functions from the QEPS-model in greater detail than previously presented. Material/Methods: The longitudinally followed GrowUpGothenburg 1990 birth cohort, with growth data from birth until adult height was analyzed, using the QEPS-model. Individual BMI-SDS values, from 3.5–8.0 years of age (n = 1901) were calculated for linear and subgroup analyses (normal /underweight, NwUw, overweight/obese, OwOb), based on the IOTF 2012 reference2. Relationships between childhood-BMI and total pubertal height gain were considered according to P-function and Q(ES)-function. Results: We found no significant difference in pubertal height gain depending on when in childhood the BMI-SDS peaked, in either sex. In general, the total pubertal growth in girls depended more on the continuous Q(ES)-function than P-function and this balance was shifted towards less P-function with higher BMI-SDS, especially for Ob girls (figure, left). NwUw boys had pubertal gain mostly from the P-function, for the Ow boys the pattern was more mixed and for Ob boys all had less P- than Q(ES)-function (figure, right). Conclusion: The results of the present study have shown that the reduced pubertal gain in height for OwOb children is not related to when during childhood the BMI peaked. For both genders, the pubertal gain shifted to less specific pubertal growth (P) and relatively more continuous growth (Q(ES)) with higher BMI-SDS.
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| 8. |
- Holmgren, Anton, et al.
(författare)
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Insight into human pubertal growth by applying the QEPS growth model.
- 2017
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Ingår i: BMC pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:107
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Tidskriftsartikel (refereegranskat)abstract
- Computerized mathematical models describing absolute and relative individual growth during puberty in both cm and standard deviation (SD)-scores are lacking. The present study aimed to fill this gap, by applying the QEPS-model that delineates mathematically the specific pubertal functions of the total growth curve.Study population used was the individual growth curves of the longitudinally followed cohort GrowUp1974 Gothenburg (n = 2280). The QEPS-model describes total height as (T)otal-function: a combination of four shape-invariant growth functions, modified by time-scale and height-scale parameters: a (Q)uadratic-function for the continuous growth from fetal life to adulthood; a negative (E)xponential-function adds the rapid, declining fetal/infancy growth; a (P)ubertal-function the specific pubertal growth spurt; a (S)top-function the declining growth until adult height. A constructed variable, MathSelect, was developed for assessing data-quality. CIs and SD-scores for growth estimates were calculated for each individual. QEPS-model estimates used for pubertal growth; from the T-function: onset of puberty as minimal height velocity (AgeT ONSET ); mid-puberty as peak height velocity (AgeT PHV ); end of puberty as height velocity decreased to 1 cm/year (AgeT END ); duration of different intervals and gain (AgeT ONSET-END and Tpubgain); from the P-function: onset of puberty, estimated as growth at 1% or 5% (AgeP1 , AgeP5); mid-puberty as 50% (AgeP50) and PHV (AgeP PHV ); end of pubertal growth at 95 or 99% (AgeP95, AgeP99); duration of different intervals and pubertal gain (Ppubgain; P max ); from the QES-function: gain (QESpubgain) . RESULTS: Application of these mathematical estimates for onset, middle and end of puberty of P-function, QES-function, and T-function during puberty showed: the later the onset of puberty, the greater the adult height; pubertal gain due to the P-function growth was independent of age at onset of puberty; boys had higher total gain during puberty due to P-function growth than to QES-function growth; for girls it was reversed.QEPS is the first growth model to provide individualized estimates of both the specific pubertal growth function and the total growth during puberty, with accompanying SD-scores and Cis for each individual. These QEPS-derived estimates enable more in-depth analysis of different aspects of pubertal growth than previously possible.
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| 9. |
- Holmgren, Anton, et al.
(författare)
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Pubertal height gain is inversely related to peak BMI in childhood.
- 2017
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Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 81:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood BMI may influence subsequent growth in height as well as the timing of puberty. The aim of the present study was to investigate associations between BMI in childhood and subsequent height gain/pubertal growth.MethodsLongitudinal growth data were used (GrowUp1990 Gothenburg cohort, n=1901). The QEPS growth-model was used to characterize height gain in relation to the highest BMISDS value between 3.5 and 8 years of age. Children were defined as overweight/obese (OwOb) or normal weight/underweight (NwUw), using the 2012 International Obesity Task Force criteria.ResultsA negative association between childhood BMISDS and pubertal height gain was observed. Already at birth, OwOb children were heavier than NwUw children, and had a greater height velocity during childhood. Onset of puberty was 3.5/3.0 months earlier in OwOb girls/boys, and they had 2.3/3.1 cm less pubertal height gain from the QEPS-models specific P-function than NwUw children. Adult height was not related to childhood BMI.ConclusionWe found that pubertal height gain was inversely related to peak BMI in childhood. Higher childhood BMISDS was associated with more growth before onset of puberty, earlier puberty and less pubertal height gain, resulting in similar adult heights for OwOb and NwUw children.
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| 10. |
- Holmgren, Anton, et al.
(författare)
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The Specific Pubertal Height Gain is Higher in Boys as Well as in Children with Lower BMISDS
- 2016
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Ingår i: Hormone Research in Paediatrics. - 1663-2818 .- 1663-2826.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Growth in height during puberty can be described by the QEPS-model as a combination of continuous basal growth, QES, and a specific pubertal growth function, P. Objective and hypotheses: To study the relationship between childhood BMISDS and the prepubertal gain and pubertal gain related to growth functions from the QEPS-model. Method: The longitudinally followed GrowUpGothenburg 1990 birth cohort, was analyzed, by the QEPS-model. Individual maximal BMISDS values, from 3.5–8.0 years of age (n=1901) were calculated for linear and subgroup analyses, underweight (blue cross), normal (blue open circles), overweight (red open circles), obese (red circles). Results: For girls (Figure left), total pubertal gain (Tpubgain) depended more on QESgain during puberty. For boys, total pubertal gain depended more on specific Pgain (Figure right). With higher BMISDS this balance was shifted towards less Pgain for both girls and boys. Before puberty, children with higher BMISDS were taller, expressed as higher QESgain, with a linear correlation over the whole BMI–range (P<0.001for both girls/ boys). Conclusion: During puberty, girls grew more due to the QES than the P functions, with opposite findings in boys. For both boys and girls, there were less Pgain and more QES- gain with higher childhood BMISDS. Before puberty, children with higher BMISDS were taller.
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