Tranexamic acid through intravenous,intramuscular and oral routes: an individual participant data meta‐analysis of pharmacokinetic studies in healthy volunteers

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.     

Additional bedtime H2‐receptor antagonist for the control of nocturnal gastric acid breakthrough: A Cochrane systematic review

OBJECTIVES: To assess the effectiveness and safety of additional bedtime H₂‐receptor antagonists (H₂RAs) in suppressing nocturnal gastric acid breakthrough (NAB) via a systematic review. METHODS: Eligible trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2004), MEDLINE (January 1966–June 2004), EMBASE (January 1980–June 2004) and CINAHL (January 1982–June 2004). Additional hand‐searching was conducted on the proceedings of correlated conferences, eight important Chinese journals and references of all included trials. All randomized controlled trials evaluating H₂RAs for the control of NAB were eligible for inclusion. The systematic review was conducted using methods recommended by The Cochrane Collaboration. RESULTS: Only two randomized crossover studies, comprising 32 participants, met the inclusion criteria. Because the design, dosage and duration of the treatments were different between the studies, it was not possible to conduct meta‐analysis. There were no consistent conclusions found between the two included studies in evaluating H₂RAs for the control of NAB. CONCLUSIONS: No implications for practice at this stage can be concluded. Appropriately designed large‐scale randomized controlled trials with long‐term follow up are needed to determine the effects of additional bedtime H₂RAs in suppressing NAB.     

DMARD combination therapy in rheumatoid arthritis: 5‐year follow‐up results in a daily practice setting

Aim: To evaluate the overall effect of disease modifying anti‐rheumatic drug (DMARD) combination therapy in daily practice. Methods: In a retrospective study, 161 consecutive files of patients who attended regular follow‐up sessions, seen from 1998, were analysed. Their data were extracted at baseline, 6 months, 1, 2, 3, 4 and 5 years. American College of Rheumatology ACR70 criteria was chosen for the evaluation of the global result. DMARD combination was methotrexate (7.5–15 mg weekly) and chloroquine (150 mg daily), with low‐dose prednisolone (less than 10 mg daily). In cases of remission, methotrexate was gradually tapered, then prednisolone. Chloroquine was discontinued after 1 year if no recurrence occurred at low‐dose (150 mg every other day). In cases of recurrence at any stage, the treatment scheme was stepped back. Results: The data of 161 patients were analysed. One hundred and six were rheumatoid factor positive (RF+) (66%). ACR 70 for all patients at 6 months follow‐up was 72.5% (95% CI = 7.0); at 1 year, 75.8% (95% CI = 6.7); at 2 years, 72.2% (95% CI = 7.2); at 3 years, 78.9% (95% CI = 6.6); at 4 years, 78.4% (95% CI = 6.9); and at 5 years, 70.6% (95% CI = 8.5). Conclusion: The classical DMARD combination therapy, when used with adequate low‐dose prednisolone, gave an ACR70 response from 71–79%. The efficacy of the treatment did not fade over time. RF– patients did better than RF+ patients, but the difference was not statistically significant.     

Per‐oral transgastric abdominal surgery

Laparoscopic surgery has several advantages over traditional surgery because it has been shown to be less invasive. The next logical step in the evolution of minimally invasive surgery may be to eliminate all abdominal incisions. The natural orifices provide a port of entry via the gastrointestinal tract to the peritoneal cavity. This approach would require the creation of a perforation, which is considered to be a major complication of endoscopy with significant morbidity and mortality. However, there are several recent studies that have described the technical feasibility and safety of a per‐oral transgastric approach to the peritoneal cavity using conventional endoscopes. Theoretically, this approach could reduce postoperative abdominal wall pain, wound infection, hernia formation, and adhesions. This article aims to summarize the current status of transgastric surgery, currently referred to as natural orifice transluminal endoscopic surgery (NOTES), and to address some of its future challenges.     

DEVELOPMENT OF INDICATORS TO MEASURE

This paper describes a study to capture the key roles and activities of nephrology nurses across different countries in Europe. The concept of the study and the need to clarify the activities of the nephrology nurse arose as part of a larger study to develop the European Practice Database (EPD) (1). The Research Board (EDTNA/ERCA) needed to identify key questions that would detect significant differences in the role and responsibilities of nephrology nurses in different countries and monitor the evolution over time of nephrology nursing practice in Europe. It was therefore appropriate to devise a separate small study to generate evidence based questions for the EPD and confirm the reliability and usefulness of the information captured.     

Sex‐related Disparity in Surgical Mortality among Pediatric Patients

Background. It has been reported that gender differences in cardiovascular outcomes found in adults also are present in children who undergo surgical repair for congenital heart disease. Methods. California statewide hospital discharge data 1989–99 were used to study outcomes in children <18 years undergoing cardiac surgery. Hospital discharge data were linked to death registry data to study postdischarge death within 30 days of discharge. We used logistic regression to evaluate the effect of gender on mortality controlling for age, race and ethnicity, type of insurance, household income, date and month of surgery, type of admission, hospital case volume, and various types of procedures. Results. There were 25 402 cardiac surgery cases with 1505 in‐hospital deaths (mortality rate of 5.92%). An additional 37 deaths occurred within 30 days after hospital discharge. Crude mortality rates for males (5.99%) and females (5.84%) were not significantly different. However, fewer neonates were female and females underwent a higher proportion of low‐risk procedures than males. Logistic regression revealed that females, compared with males, had a significantly higher odds ratio (OR) for in‐hospital mortality (OR = 1.18, P < .01) and overall (up to 30 days post discharge) mortality (OR = 1.18, P < .01). The risk‐adjusted length of hospital stay was similar between females and males while charges per hospital day were slightly higher in females than males. The prevalence of Down syndrome, pulmonary hypertension, and failure to thrive were higher in females. Conclusions. Female gender is associated with an 18% higher in‐hospital and 30‐day postdischarge mortality as compared with male gender. There was no difference in length of hospital stay between males and females. The mechanism by which female gender acts as a risk factor requires further investigation.