What information and the extent of information research participants need in informed consent forms: a multi-country survey.

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

OBJECTIVE: To review available data on tranexamic acid (TXA) plasma concentration needed to inhibit fibrinolysis and the time to achieve this concentration when giving TXA by different routes in humans. To identify ongoing trials assessing alternatives to intravenous TXA administration. METHODS: We updated two previous systematic reviews by searching MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to July 2021. We also searched the WHO International Clinical Trials Registry Platform for ongoing trials to July 2021. Titles and abstracts were screened for relevant trials. Two reviewers independently reviewed and agreed the trials to be included. RESULTS: Plasma TXA concentrations over 10 mg/L provide near maximal inhibition of fibrinolysis, with concentrations over 5 mg/L providing partial inhibition. Oral TXA tablets take about 1 h to reach a plasma concentration of 5 mg/L in postpartum women. Studies in healthy volunteers and shocked trauma patients show that intramuscular TXA achieves a plasma level of over 10 mg/L within 15 min. One trial is ongoing to determine the pharmacokinetics of intramuscular and oral solution TXA in pregnant women. CONCLUSION: Intramuscular TXA in healthy volunteers and shocked trauma patients reaches therapeutic concentration rapidly. Oral TXA tablets take too long to reach the minimum therapeutic concentration in postpartum women.

Plasma Concentrations of Tranexamic Acid in Postpartum Women After Oral Administration.

OBJECTIVE: To evaluate the pharmacokinetics of tranexamic acid after oral administration to postpartum women. METHODS: We conducted a single-center pharmacokinetic study at Teaching Hospital-Jaffna, Sri Lanka, on 12 healthy postpartum women who delivered vaginally. After oral administration of 2 g of immediate-release tranexamic acid 1 hour after delivery, pharmacokinetic parameters were measured on plasma samples at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours. Plasma tranexamic acid concentrations were determined by high-performance liquid chromatography. The outcome measures were maximum observed plasma concentration, time to maximum plasma concentration, time to reach effective plasma concentration, time period effective serum concentration lasted, area under the curve for drug concentration, and half-life of tranexamic acid. RESULTS: The mean maximum observed plasma concentration was 10.06 micrograms/mL (range 8.56-12.22 micrograms/mL). The mean time to maximum plasma concentration was 2.92 hours (range 2.5-3.5 hours). Mean time taken to reach the effective plasma concentration of 5 micrograms/mL and the mean time this concentration lasted were 0.87 hours and 6.73 hours, respectively. Duration for which plasma tranexamic acid concentration remained greater than 5 micrograms/mL was 5.86 hours. Half-life was 1.65 hours. Area under the curve for drug concentration was 49.16 micrograms.h/mL (range 43.75-52.69 micrograms.h/mL). CONCLUSION: Clinically effective plasma concentrations of tranexamic acid in postpartum women may be achieved within 1 hour of oral administration. Given the promising pharmacokinetic properties, we recommend additional studies with larger sample sizes to investigate the potential of oral tranexamic acid for the treatment or prophylaxis of postpartum hemorrhage.

Euglycaemic ketoacidosis in a non-diabetic primigravida following an appendicectomy.

Pregnancy creates significant alterations in energy metabolism which itself is a physiological adaptation to provide continuous flow of energy metabolites to the foetus. The state of insulin resistance created by hormonal changes in pregnancy enables free flow of glucose to the foetus and allows its absorption through facilitated diffusion. As glucose is preferentially available for the foetus, maternal fasting glucose level would be less than that of a non-pregnant state and in contrast plasma ketones and free fatty acids levels are elevated, resulting in a state of accelerated starvation. These metabolic alterations place a pregnant woman at a higher risk of developing euglycaemic ketoacidosis when allowed to fast for prolonged periods due to medical, surgical and psychological reasons. We report a rare case of euglycaemic ketoacidosis causing severe increased anion gap metabolic acidosis in a non-diabetic mother following surgery for appendicitis at a gestation of 27 weeks.