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11.
Tao Zhang Hua Cheng Zhenyu Pan Jie Mi Yuzhu Dong Ying Zhang Dan Sun Qian Du Xiaoliang Cheng Yalin Dong 《Basic & clinical pharmacology & toxicology》2020,126(1):75-85
A vancomycin steady‐state trough concentration (Cmin) of 15‐20 mg/L is recommended for achieving a ratio of the 24‐hour area under the curve to the minimum inhibitory concentration (AUC0‐24/MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between Cmin and AUC0‐24/MIC in paediatric patients. Population‐based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between Cmin and the calculated AUC0‐24/MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body‐weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, Cmin ranges of 5.0‐5.9 and 9.0‐12.9 mg/L were associated with AUC0‐24/MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a Cmin of 5.0‐5.9 mg/L and AUC0‐24/MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved Cmin of 9.0‐12.9 mg/L and AUC0‐24/MIC ≥400 in 2.0‐ and 1.6‐fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin Cmin values of 5.0‐12.9 mg/L were strongly predictive of achieving AUC0‐24/MIC ≥400, and rational dosing regimens of 10‐15 mg/kg q6h were required in paediatric patients, depending on the pathogen. 相似文献
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E Bellacchio R Stallone T Palladino S Mastroianno L Zelante M Sacco V Trischitta M Carella 《Clinical genetics》2013,83(1):83-87
Delvecchio M, Ludovico O, Bellacchio E, Stallone R, Palladino T, Mastroianno S, Zelante L, Sacco M, Trischitta V, Carella M. MODY type 2 P59S GCK mutant: founder effect in South of Italy. Mutations in the glucokinase (GCK) gene are the most frequent cause of maturity onset diabetes of the young (MODY) in Italy. We evaluated GCK mutations in 32 unrelated patients younger than 18 years who had been diagnosed with MODY. Eleven different GCK heterozygous mutations were identified in 22 (68.7%) of the 32 probands. Nine mutations were missense and two were nonsense. Three of these mutations (E17X, P59S and E372X) have not been described previously and were shown to be associated with hyperglycaemia. Several prediction methods suggested that the E17X and E372X mutations result in a premature truncated protein and that the P59S mutation is pathogenic. This idea was further supported by evidence suggesting that Proline 59 is a highly conserved amino acid residue and that the P59S mutation does not appear to be present in non‐diabetic controls and in sequence variant databases. Furthermore, this mutation was found in six (27.3%) of the patients from the same geographical area, Gargano, pointing to the existence of a founder effect, which was confirmed by microsatellite analysis. 相似文献
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R. Wu J. Zhang J. Sun M. Zhou J. S. Wu N. Li X. Li K. H. Luke M.‐C. Poon V. S. Blanchette N. L. Young 《Haemophilia》2014,20(6):794-799
It is important to assess the health‐related quality of life outcomes of boys in China, but there are no tools validated for this purpose. The objective of the study was to assess the validity of the Simplified Chinese version of the CHO‐KLAT2.0. We recruited 60 boys with either haemophilia A (HA) or haemophilia B (HB) and their parents from four regions in China, and assessed the validity of CHO‐KLAT compared to the PedsQL. All participants complete the CHO‐KLAT a second time 1–2 weeks later to assess reliability. The boys ranged in age from 7 to 18 (mean = 12.4; SD = 3.03) years. The severity distribution was: mild (9), moderate (10) and severe (41). On‐demand therapy was received by 26 boys, while 18 received low‐dose prophylaxis (HA: 10 IU kg?1 2–3 times week?1, and HB: 20 IU kg?1 1 time week?1). The mean CHO‐KLAT scores were 63.7 (SD = 10.6) for child‐report and 58.3 (SD = 11.4) for parent‐report. Validity was supported by a correlation of 0.67 (P < 0.0001) with the PedsQL for child‐report and 0.64 (P < 0.0001) for parent‐report. The test–retest reliability was 0.88 (95% CI: 0.82–0.94) for child‐report, and 0.90 (95% CI: 0.86–0.95) for parent‐report. Inter‐rater reliability was 0.46 (95% CI: 0.26–0.66). CHO‐KLAT scores were 11 points higher among patients who had been on prophylaxis 3 times per week for ≥24 weeks. These results confirm the reliability and validity of the Chinese version of the CHO‐KLAT. This measure is suitable for use in prospective clinical trials in boys with haemophilia in China. 相似文献
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Frank S. Pidcock 《Developmental neurorehabilitation》2013,16(4):298-302
Purpose: To review the use of therapeutic botulinum toxin type A (BoNT-A) treatments in uncommon neurogenetic syndromes.Method: A retrospective questionnaire and interview study of a selected case series to assess the efficacy and safety following initial BoNT-A treatment (50–400 units per subject) was conducted to determine the response of families to treatment. Twelve male and six female subjects with ages from 2–19 years were included. The reasons for treatments were based on both patient-related and caregiver-related objectives. Satisfaction with achievement of stated goals was assessed by follow-up interviews.Results: Beneficial effects were reported in 56%, some effects in 22% and no to minimal effects in 22%. The duration of effect ranged from 10 days to 12 months with an average of 3.16 months. Ten families would repeat the injections as needed, four would not and four were not sure. Unanticipated effects of BoNT-A treatments were reported by some families. Adverse effects did not occur with the doses that were used.Conclusions: The results suggest that obtaining family input may be useful when treating spasticity in unusual circumstances. The use of BTX-A in uncommon neurogenetic syndromes was supported by the majority of families interviewed. 相似文献
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