Intracapsular pressure in children with septic arthritis of the hip.

Elevated intracapsular pressure in the hip causes occlusion of the retinacular vessels and may result in avascular necrosis of the proximal femoral epiphysis (ANPFE) and growth disturbances. Our goal is to study intraarticular pressure in children with septic arthritis of the hip and its potential correlation with body weight, systemic blood pressure and the volume of synovial fluid aspirated from the joint. Thirteen septic arthritis of the hip were studied. Inclusion criteria: pain, limping, fever, leukocytosis, elevated C-reactive protein and ultrasonographic effusion >5 mm. Traumatic, inflammatory, rheumatic or tumoral origin were excluded. Mean age was 3.7 years. Girls were 58%. Mean time to articular drainage was 15 h. Arthrocentesis was performed. An STIC self-calibrating monitoring system with an error of ±1 mmHg was used. Measurements were taken: intracapsular pressure, volume of fluid aspirated, systolic and diastolic pressures and weight. Follow-up was 6.3 years. Descriptive and nonparametric tests were performed: U Mann-Whitney and Kruskal-Wallis. Statistical significance was P <0.05. Mean intracapsular pressure was 50.5 mmHg; fluid aspirated was 2.9 ml; systolic and diastolic pressures were 107.5 and 44.3 mmHg, respectively; weight was 16.2 kg. Intracapsular pressure exceeded 30 mmHg in eight children (61.5%) and was lower than 50 mmHg in 73%. Variables studied had no significance on intracapsular pressure. Complications: coxa magna in three patients (23%) and Harris lines in three (23%). Surgical drainage of septic arthritis of hip must be performed urgently, within the first 24 hours, to reduce the time with high intracapsular pressure and to avoid risk of ANPFE.

Conversion from Prograf to Advagraf in adolescents with stable liver transplants: comparative pharmacokinetics and 1-year follow-up.

The recommended dose of Advagraf for conversion from Prograf is considered to be 1:1 on a milligram basis. However, the long-term equivalence of Prograf and Advagraf has been questioned. The relative bioavailability of Advagraf and Prograf was evaluated in a single-center, open-label study of Prograf-to-Advagraf conversion in 20 patients, ranging in age from 12 to 18 years, who had a stable liver transplant and were receiving Prograf. After the supervised administration of Prograf for 7 days, the patients were converted to Advagraf. On days 7 and 14, serial blood samples were obtained for tacrolimus determinations. The pharmacokinetic parameters were calculated with a noncompartmental approach, and the relative bioavailability of both formulations was calculated according to standard statistical methods. Polymorphisms in cytochrome P450 3A5 (rs776746), adenosine triphosphate-binding cassette B1 (rs1045642), POR*28 (rs1057868), and POR (rs2868177) were determined with standard methods. The clinical and analytical data from a 1-year follow-up period were collected for all patients 30, 90, 180, and 360 days after conversion. The mean ratios for Cmax and AUC0-24 were 96.9 (90% confidence interval = 85.37-110.19) and 100.1 (90% confidence interval = 90.8-112.1), respectively. No relationship was found between the patients' genotypes and the pharmacokinetic tacrolimus values. During the follow-up, biochemical parameters (aspartate aminotransferase, alanine aminotransferase, bilirubin, cystatin C, and creatinine) did not change significantly; 3 patients presented with relevant clinical events, but no event was considered to be related to tacrolimus. A decrease in tacrolimus blood levels and an increase in dose/level ratios were observed 3 and 6 months after conversion, but they returned to basal levels by month 12. In conclusion, conversion from Prograf to Advagraf with a 1:1 dose equivalence is appropriate as an initial guideline. Our 1-year follow-up showed a transient decrease in tacrolimus levels, so closer monitoring of tacrolimus levels may be required after conversion.

Overuse of PPIs in patients at admission, during treatment, and at discharge in a tertiary Spanish hospital.

BACKGROUND: The first generic PPI was introduced in Spain in 2001, and since then their prescriptions have increased steadily by about 200%. AIM: To evaluate the frequency of use and the appropriateness of indications of PPIs in hospitalised patients, and possible factors predicting their use. We also evaluated relevant PPI-drug interactions and serious adverse drug reactions (SADRs). METHODS: This was a cross-sectional, prescription-indication drug-utilisation study in hospitalised patients with follow-up until discharge. Sampling was random and stratified by services, and was calculated to obtain an error in the precision of prescription of ±4% with a 95% confidence interval with maximum variability (50%). RESULTS: 328 patients were included; 28.65% were prescribed a PPI at admission, 82.62% were prescribed a PPI during hospitalisation, and 54.75% at discharge, with inappropriate indications in 74.47%, 61.25% and 80.24% respectively. The OR of being discharged with PPIs was 3.01(95% CI:2.17-4.18, p=0.000). The inappropriate indication most frequently seen at admission and at discharge was antiplatelet therapy. During hospitalisation it was prophylaxis for stress ulcer in patients at low risk. PPI prescription at admission remained at discharge in 75.90% of cases, 73.02% without an acceptable indication. Being >64 years old, taking >4 drugs, co-medication (NSAIDs, antiaggregation and anticoagulation), certain hospital departments and length of stay >15 days predicted 83.7% of prescriptions at discharge. Four relevant PPI-drug interactions were found, and 2 resulted in SADRs, thus the incidence per 1, 000 patients was 2.66 (Poisson 95% CI:0.62-7.23). CONCLUSIONS: There was a very high frequency of overuse of PPIs in inpatients and outpatients. Hospitalisation did not represent an opportunity for better prescription of PPIs.

Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram.

We investigate the impact of sex and genotype on citalopram disposition in 35 healthy volunteers who received an oral dose of 20mg citalopram within a single-dose bioequivalence study. CYP2C19*2 and *3, and CYP2D6*4 mutations were determined by Real-Time PCR. The influence of sex and genotype was analyzed by a linear mixed model for repeated measures, including formulation, period, sequence, sex, CYP2C19 and CYP2D6 as fixed effects and subject nested sequence*sex*CYP2C19*CYP2D6 as the random one. Pharmacokinetic parameters were log-transformed and AUC(infinity) and C(max) adjusted to the administered dose/weight. The model yields a statistical significance in AUC(infinity) and CL/F for CYP2C19 and CYP2D6. Gender, formulation, sequence or period effects were not statistically significant. AUC(infinity) of CYP2C19*1/*2 and CYP2C19*2/*2 carriers is 44% and 118% higher than wild type, respectively; CYP2D6 volunteers carrying 1/4 have an AUC 23% higher than wild type. Our data also suggest that the influence of CYP2D6 on AUC(infinity) is very low when it is in association with CYP2C19*1/*1 while its influence is more apparent in association with CYP2C19*1/*2. In conclusion, we demonstrate the influence of CYP2C19 and CYP2D6 in the disposition of citalopram, and we suggest that the influence of CYP2D6 is more probable in volunteers with at least one defective allele of CYP2C19.