Background: Visual estimation of blood loss following delivery often under-reports actual bleed volume. To improve accuracy, quantitative blood loss measurement was introduced for all births in the 12 hospitals providing maternity care in Wales. This intervention was incorporated into a quality improvement programme (Obstetric Bleeding Strategy for Wales, OBS Cymru). We report the incidence of postpartum haemorrhage in Wales over a 1year period using quantitative measurement. Methods: This prospective, consecutive cohort included all 31,341 women giving birth in Wales in 2017. Standardised training was cascaded to maternity staff in all 12 hospitals in Wales. The training comprised mockscenarios, a video and team drills. Uptake of quantitative blood loss measurement was audited at each centre. Data on postpartum haemorrhage of > 1000 mL were collected and analysed according to mode of delivery. Data on blood loss for all maternities was from the NHS Wales Informatics Service. Results: Biannual audit data demonstrated an increase in quantitative measurement from 52.1 to 87.8% (P < 0.001). The incidence (95% confidence intervals, CI) of postpartum haemorrhage of > 1000 mL, > 1500 mL and > 2000 mL was 8.6% (8.3 to 8.9), 3.3% (3.1 to 3.5) and 1.3% (1.2 to 1.4), respectively compared to 5%, 2% and 0.8% in the year before OBS Cymru. The incidence (95% CI) of bleeds of > 1000 mL was similar across the 12 hospitals despite widely varied size, staffing levels and case mix, median (25th to 75th centile) 8.6% (7.8-9.6). The incidence of PPH varied with mode of delivery and was mean (95% CI) 4.9% (4.6-5.2) for unassisted vaginal deliveries, 18.4 (17.1-19.8) for instrumental vaginal deliveries, 8.5 (7.7-9.4) for elective caesarean section and 19.8 (18.6-21.0) for non-elective caesarean sections. Conclusions: Quantitative measurement of blood loss is feasible in all hospitals providing maternity care and is associated with detection of higher rates of postpartum haemorrhage. These results have implications for the definition of abnormal blood loss after childbirth and for management and research of postpartum haemorrhage.

Background Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH (> 2500 mL) and the need for red cell transfusion. Methods A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 (n = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH (> 2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data. Results Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH > 1000 mL, whilst ROTEM use for PPH > 1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year (P = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), (P = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year (P = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) (P = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment. Conclusions The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.

BackgroundPostpartum haemorrhage (PPH) contributes to substantial maternal morbidity. Research into PPH has led to improvements in care which have been incorporated into the Obstetric Bleeding Strategy for Wales.InterventionA national quality improvement team supported local teams in implementing multiple interventions including risk assessment, objective measurement of blood loss, multiprofessional assessment (at the bedside at 1000 mL blood loss) and point-of-care (POC) testing of coagulation to guide blood product resuscitation during PPH. The project was rolled out to all 12 obstetric units in 2017. The interventions were reinforced by an All Wales Guideline, PPH proforma and standardised training. A national database, biannual audits, and patient and staff surveys reported process and outcome measures.ResultsProcess measures: during 2017, there was an increase in the percentage of maternities with documented risk assessment (0%–76%), objective measurement of blood loss (52%–88%) and POC testing for coagulation for PPH ≥1500 mL (38%–59%). Maternity staff survey indicated that 94% were aware of the project and 87% stated that it had changed their unit’s management of PPH. Interim outcome measures: the incidence (95% CI) of PPH ≥2500 mL per 1000 maternities in 2017 was 6.03 (5.23–6.95). The annual number of women receiving any red blood cell transfusion, level 3 intensive care admission and hysterectomy for PPH was 19.7 (18.2 to 21.3), 0.702 (0.464 to 1.06) and 0.255 (0.129 to 0.504) per 1000 maternities, respectively.ConclusionsA high level of project awareness across Welsh maternity units has been achieved. Measurement of blood loss was reported to be the most important early change in practice, while PPH documentation and POC testing continue to be embedded. Combining qualitative and quantitative measures to inform implementation has improved project delivery and allowed teams to adapt to local contexts.

Bio-isosteric replacement is a frequently used tool in medicinal chemistry. While the pharmacological activity is not influenced by the exchange of substituents, the solid-state characteristics and formation of different crystal forms may well be altered dramatically, jeopardizing the processability and safety of the drug compound. In this study we investigate a series of triphenylimidazole (TPI) derivatives as model compounds with the bio-isosteric exchange of only one halogen position (F, Cl, Br, I). Crystallization from two industrially used solvents (methanol and acetonitrile) reveals solvate formation of all TPIs, for which the basic hydrogen bonded motif does not change. The three-dimensional packing depends on the size of the substituent and changes from fluoroto chloro-and bromo-substitution but remains the same for the larger iodo-substituent. From acetonitrile, only F-TPI and Cl-TPI form an isomorphic channel solvate, which in both cases desolvates reversibly to an isomorphic crystal form. Due to the halogen atom lining of the channels, bromine and iodine are too large to generate a stable packing. This study illustrates the importance of understanding the influence of bio-isosteric substitution on the solid state, in order to best utilize this common tool.

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