Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed size. METHODS: Women with PPH 1000-1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused. RESULTS: Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3-1.7), P =0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th-75th centile) of 1 (0-4.5) unit of allogeneic blood products and had an additional 300 (100-350) ml blood loss whereas those who received placebo also received 3 (0-6) units of allogeneic blood products and had 700 (200-1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group. CONCLUSIONS: Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre -1 , but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis. TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 , last accessed 5 July 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-005511-11 , last accessed 5 July 2017).

Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study.

BACKGROUND: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. Based on data from trauma studies, empirical infusions of fresh frozen plasma (FFP) are often given during severe PPH if coagulation tests are unavailable. This study observed a cohort of women with moderate/severe PPH in whom FFP infusion was guided by the use of viscoelastometric point-of-care testing (VE-POCT) and clinical assessment. METHODS: Women were enrolled into this observational study when blood loss was measured or suspected to be about 1000 mL. If Fibtem A5 determined by Rotem ® thromboelastometry remained >15 mm, or bleeding stopped, FFP was withheld. If Fibtem A5 was ≤15 mm and bleeding ongoing, women were randomized into an interventional study as previously reported. Clinical and laboratory outcomes were recorded. RESULTS: The study recruited 605 women and 98% had FFP withheld. The median (25 th -75 th centile) total blood loss was 1500 (1300-2000) mL with 300 (50-545) mL occurring after enrolment. Total blood loss was >2500 mL in 40/605 (6.6%) women. RBCs were transfused in 141/605 (23.3%) patients and 11 (1.8%) received ≥4 units. At least one invasive procedure was performed in 283/605 (46.8%) women. Level 3 care was required for 10/605 (1.7%) women. No women developed clinically significant haemostatic impairment. CONCLUSIONS: Restrictive use of FFP guided by clinical assessment of bleeding and VE-POCT is feasible and did not result in clinically significant haemostatic impairment. Studies should compare the clinical and cost effectiveness of empirical FFP infusions, according to current guidelines, with targeted use of FFP based on VE-POCT. CLINICAL TRIAL REGISTRATION: ISRCTN46295339 ( http://www.isrctn.com/ISRCTN46295339 ) (accessed July 24, 2017), EudraCT 2012-005511-11 ( https://www.clinicaltrialsregister.eu/ctr-search?query=2011-005511-11 ) (accessed July 24, 2017).

Fissure Seal or Fluoride Varnish? A Randomized Trial of Relative Effectiveness.

Fissure sealant (FS) and fluoride varnish (FV) are effective in preventing dental caries when compared with a no-treatment control. However, the relative clinical effectiveness of these interventions is uncertain. The objective of the study was to compare the clinical effectiveness of FS and FV in preventing dental caries in first permanent molars (FPMs) in 6- to 7-y-olds. The study design was a randomized clinical trial, with 2 parallel arms. The setting was a targeted-population program that used mobile dental clinics in schools located within areas of high social and economic deprivation in South Wales. A total of 1,016 children were randomized 1:1 to receive either FS or FV. Resin-based FS was applied to caries-free FPMs and maintained at 6-mo intervals. FV was applied at baseline and at 6-mo intervals for 3 y. The main outcome measures were the proportion of children developing caries into dentine (D4-6MFT) on any 1 of up to 4 treated FPMs after 36 mo. At 36 mo, 835 (82%) children remained: 417 in the FS arm and 418 in the FV arm. A smaller proportion of children who received FV ( n = 73, 17.5%) versus FS ( n = 82, 19.6%) developed caries into dentine on at least 1 FPM (odds ratio [OR] = 0.84; 95% CI, 0.59 to 1.21; P = 0.35), a nonstatistically significant difference between FS and FV treatments. The results were similar when the number of newly decayed teeth (OR = 0.86; 95% CI, 0.60 to 1.22) and tooth surfaces (OR = 0.85; 95% CI, 0.59 to 1.21) were examined. In a community oral health program, semiannual application of FV resulted in caries prevention that was not significantly different from that obtained by applying and maintaining FS after 36 mo (EudraCT: 2010-023476-23; ISRCTN: ISRCTN17029222).