Are prophylactic antibiotics necessary with clean intermittent catheterization? A randomized controlled trial

Background/Purpose

Clean intermittent catheterization has been an established practice for more than 3 decades. The validity of antibiotic prophylaxis has been questioned although not tested.

Methods

Eighty-five patients were recruited into a randomized controlled trial. The randomization involved the placement into 1 of 2 groups: (A) continuing antibiotics or (B) discontinuing antibiotics. The trial would last 4 months with the outcome being a confirmed urinary tract infection. All groups were matched for age, sex, and pathology.

Results

The incidence of urinary tract infections was significantly increased in the group who continued to use antibiotics (n = 20) when compared with the group who discontinued prophylaxis (n = 3). The common infecting organism was Escherichia coli.

Conclusions

The use of prophylactic antibiotics for children who intermittently catheterize may not be necessary. The use of prophylactic antibiotics may result in increased rates of infection because of the development of resistant organisms.     

Estimation of glomerular filtration rate in paediatric cancer patients using 51CR-EDTA population pharmacokinetics

Estimation of glomerular filtration rate (GFR) using the clearance of chromium 51 EDTA ((51)Cr-EDTA) (or other radiolabelled isotopes) is reliable, but invasive and not always practicable. Mathematical models have been devised for estimating GFR using readily obtainable patient characteristics. Unfortunately, these models were developed using various patient populations and may not provide the optimal prediction of GFR in children with cancer. The current study uses population pharmacokinetics to determine the relationship between (51)Cr-EDTA clearance, and patient covariates in 50 paediatric cancer patients. These models were validated using a separate group of 43 children and were compared with previously published models of renal function. Body size was the major determinant of (51)Cr-EDTA clearance and inclusion of weight or surface area reduced the residual variability between individuals (coefficient of variation) from 61 to 32%. Serum creatinine was the only other parameter that significantly improved the model. Mean percentage error values of -5.0 and -1.1% were observed for models including weight alone or weight and creatinine, respectively, with precision estimates of 21.7 and 20.0%. These simple additive models provide a more rationale approach than the use of complex formulae, involving additional parameters, to predict renal function.     

Chemotherapy individualization

The current practice of dosing patients with anticancer drugs based on body size, leads to a large degree of inter-patient variation in clinical outcome following standard doses of chemotherapy. Some patients may fail to respond to treatment, whilst others experience unacceptable side effects. Recent studies have identified more rational approaches to drug dosing, based on patient characteristics such as renal function, pharmacogenetic factors, and drug metabolizing activity. These can be used together with therapeutic drug monitoring and adaptive dosing to achieve a targeted systemic drug exposure in each patient, which may lead to more consistent clinical outcomes in patients receiving comparable chemotherapy dosing regimens. The purpose of this review is to present some approaches to chemotherapy individualization, examples of how this might be applied, and speculation as to how recent advances in pharmacogenetics may lead to further dose-optimization.Whilst it is hoped that the design of new agents, targeted to specific genes involved in oncogenesis, will lead to increased success in the treatment of cancer patients, it is essential that the drugs currently available are used to their maximum potential.     

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.     

Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion

PURPOSE: The pharmacokinetics and metabolism of cyclophosphamide (CPA) when given as a 1-h and a 24-h infusion to children were compared. METHODS: Thirteen children with a variety of different malignancies received an identical dose of cyclophosphamide as a 1- and 24-h infusion. In each case the concentration of CPA and its principal metabolites were measured by a thin-layer-chromatography-photographic-densitometry technique. RESULTS: Cyclophosphamide clearance was greater during the 24-h infusion, following time-dependent increases in the metabolism of the drug (autoinduction) (median 5.1 vs 3.1 l/h/m2: P = 0.037). Autoinduction was seen in five children (38%), producing a median end of infusion concentration of 49% (range 28-89%) of the maximum and was not accompanied by an increase in the production of the principal inactive metabolites carboxyphosphamide and dechloroethylcyclophosphamide. CONCLUSIONS: These results suggest potential benefits of prolonging the infusion of CPA in clinical practice.     

Intraventricular haemorrhage in the preterm infant without hyaline membrane disease

The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) ('IVH only') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of 'IVH only' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks' gestation. Infants with 'IVH only' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from 'IVH only' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with 'IVH only' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the 'IVH only' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.     

超长段尿道狭窄术后勃起功能的评估

目的 探讨自体组织替代治疗超长段尿道狭窄对勃起功能的影响.方法 回顾性分析2007年1月至2009年1月采用不同自体组织补片(阴囊纵隔、包皮内板、口腔黏膜)Onlay术式替代治疗超长段男性尿道狭窄患者的临床资料,并随访患者ⅡEF-5评分、QOL评分及最大尿流率,并与术前相应情况进行分析.结果 根据研究标准收集23份有效数据.患者术前及术后3、6、12个月QOL评分分别为5.22±0.75、1.22±1.40、1.82±1.17、2.07±0.46,最大尿流率分别为(3.93±3.62)、(22.46±4.65)、(23.81±6.22)、(21.52±7.44)ml/s,术后不同时期均较术前明显改善(P＜0.01).术前及术后3、6、12个月ⅡEF-5评分分别为14.47±9.55、14.70±5.32、14.26±3.29和14.58±3.62,组间比较差异无统计学意义(P＞0.05).9例狭窄部位累及至后尿道者术后3、6、12个月ⅡEF-5评分分别为11.67±2.59、12.35±1.83、13.19±1.67,14例单纯前尿道狭窄者分别为17.79±6.42、16.57±4.78、16.01±3.85,2组间比较差异均有统计学意义(P＜0.05).狭窄累及后尿道患者多元线性回归分析中,年龄、受伤时间及尿道狭窄段长度与替代术后ⅡEF-5评分呈多元线性相关.结论 自体组织替代治疗男性超长段尿道狭窄对勃起功能影响不明显;狭窄段累及后尿道时可能对患者勃起功能产生一定影响.患者年龄和受伤时间对勃起功能有协同影响作用.

Abstract：

Objective To investigate the effect of substitutive reconstruction of long urethral stricture on male erectile function. Methods From January 2007 to January 2009, 23 patients with anterior or posterior long urethral stricture were accepted for a variety of onlay substitutive procedures, including lingual mucosa, perputial skin, and mid-scrotal skin. During the follow-up, data from the International Index of Erectile Function-5 (ⅡEF-5) questionnaire and the Quality of Life (QOL) questionnaire as well as maximal flow rate were recorded. All data were compared with those obtained before surgery. Results Significant improvement in QOL (1.22 ± 1.40, 1.82 ± 1. 17,2.07± 0.46) and maximal flow rate (22.46± 4.65, 23.81 ± 6.22, 21.52 ±7.44 ) could be observed 3, 6 and 12 months after surgery compared with those before surgery (5. 22 ± 0. 75, 3. 93 ± 3. 62)(P＜0.01). No significant differences in the responses to the ⅡEF-5 questionnaire were observed among all patients during the follow-up (P＞0. 05). At the 3, 6 and 12 months after procedure,scores of ⅡEF-5 in patients with anterior urethral stricture ( 17.79 ± 6.42, 16. 57 ± 4. 78, 16.01 ±3.85) were significantly higher than those with posterior urethral stricture (11.67 ± 2.59, 12.35 ±1.83,13. 19±1.67, P＜0.05). In patients with posterior urethral stricture, the multiple linear regression showed that age, time interval of injury and length of stricture were related to the ⅡEF-5score (P＜0.05). Conclusions Substitutive reconstruction for treating the long urethral stricture has little effect on male erectile function. But the location of stricture, especially extended to posterior urethra, may have impact on the erectile function.