Small volume resuscitation with 20% albumin in intensive care: physiological effects : The SWIPE randomised clinical trial.

PURPOSE: We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4-5% albumin. METHODS: We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK. RESULTS: The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4-5% albumin group [median difference - 600 ml, 95% confidence interval (CI) - 800 to - 400; P < 0.001]. The 20% albumin group had lower cumulative fluid balance at 48 h (mean difference - 576 ml, 95% CI - 1033 to - 119; P = 0.01). Peak albumin levels were higher but sodium and chloride levels lower in the 20% albumin group. Median (interquartile range) duration of mechanical ventilation was 12.0 h (7.6, 33.1) in the 20% albumin group and 15.3 h (7.7, 58.1) in the 4-5% albumin group (P = 0.13); the proportion of patients commenced on renal replacement therapy after randomization was 3.3% and 4.2% (P = 0.67), respectively, and the proportion discharged alive from ICU was 97.4% and 91.1% (P = 0.02). CONCLUSIONS: Resuscitation with 20% albumin decreased resuscitation fluid requirements, minimized positive early fluid balance and was not associated with any evidence of harm compared with 4-5% albumin. These findings support the safety of further exploration of resuscitation with 20% albumin in larger randomised trials. TRIAL REGISTRATION: http://www.anzctr.org.au . Identifier ACTRN12615000349549.

A novel inexpensive electrochemical sensor for pyrazinoic acid as a potential tool for the identification of pyrazinamide-resistant Mycobacterium tuberculosis.

Introduction: Tuberculosis (TB) is a significant cause of morbidity and mortality worldwide. The patient compliance with the long treatment regimens is essential for successful eradication. Pyrazinamide (PZA) shortens these regimens from 9 to 6 months, and therefore, improves treatment completion rates. Although PZA is a first-line medication for the treatment of TB, no simple or reliable assay to determine PZA resistance is yet available. In the presence of PZA, only susceptible Mycobacterium tuberculosis strains release pyrazinoic acid (POA). Therefore, the measurement and quantification of released POA is an indicator of PZA resistance. Methods: Two electrochemical sensors were constructed and tested with alternative working electrodes in conjunction with a portable potentiostat to measure the current produced when a potential difference of 2 V is applied to varying concentrations of POA in controlled solutions. Results: The large (13.2 mm) electrochemical sensor was able to detect POA at a minimum concentration of 40 µM to a statistically significant level (P = 0.0190). Similar graphical trends were obtained when testing the electrochemical sensor in the supernatant of a negative microscopic observation drug susceptibility assay culture, irrespective of the presence of PZA. Conclusion: Inexpensive and reusable electrochemical sensors with a portable potentiostat are a promising tool for the detection of POA, a biomarker of PZA susceptible M. Tuberculosis.

Placental Features of Late-Onset Adverse Pregnancy Outcome.

OBJECTIVE: Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement. METHODS: Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium). RESULTS: Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10-12) vessels/mm2 vs. normal outcome 13 (12-15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19-50) nM vs. 12 (6-24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11-50) vs. 55 (24-102) mIU/mg, p = 0.007) and human placental lactogen (11 (6-14) vs. 27 (9-50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13-29) vs. 5 (2-15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue. CONCLUSION: These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may improve its prediction.

Irritable bowel syndrome: a comparison of subtypes.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is traditionally divided into subtypes depending on the bowel habit abnormality, but there is little clarity in the literature about whether these subtypes differ symptomatically or psychologically. Furthermore, there are conflicting reports on the relationship between symptom severity and psychological status. The aim of this study was to address these issues in a large cohort of patients defined by bowel habit. METHODS: One thousand IBS patients were divided into diarrhea (IBS-D), constipation (IBS-C), and mixed (IBS-M) bowel habit subtypes and completed a series of validated questionnaires capturing symptom severity, non-colonic symptomatology (somatization), quality of life, and anxiety or depression levels. Comparisons were made using SPSS version 20. RESULTS: There were no significant differences between the three subtypes with respect to symptom severity, abdominal pain intensity, non-colonic symptomatology, quality of life, and anxiety or depression scores (all Ps > 0.05). In addition, there was only a small but statistically significant correlation between IBS symptom severity and both anxiety or depression, as well as quality of life (highest r = 0.34), while the relationship between somatization and disease severity was moderate (r = 0.42). CONCLUSION: This study suggests that there are no differences in the symptom profiles and anxiety or depression scores between different subtypes of IBS. In addition, anxiety and depression do not appear to be strongly associated with symptom severity, although this does not exclude the possible interplay between these and other psychological drivers of severity, such as poor coping skills.