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The impact of the Safe Delivery Application on knowledge and skills managing postpartum haemorrhage in a low resource setting: a cluster randomized controlled trial in West Wollega region, Ethiopia
Christiansen, A. H., Sørensen, B. L., Boas, I. M., Bedesa, T., Fekede, W., Nielsen, H. S., Lund, S.
Reproductive health. 2023;20(1):91
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Abstract
BACKGROUND Postpartum haemorrhage is one of the leading causes of maternal mortality in low-income countries. Improving health workers' competencies in obstetric emergencies in low-income settings, has been recognized as an important factor in preventing maternal mortality and morbidity. mHealth interventions in maternal and newborn health care has shown the potential to improve health service delivery. Strong study designs such as randomized controlled trials are missing to estimate the effectiveness of the mHealth interventions. METHODS Between August 2013 and August 2014, 70 health facilities in West Wollega Region, Ethiopia were included and randomized to intervention or control in a cluster randomized controlled trial. At intervention facilities birth attendants were provided with a smartphone with the SDA installed. Of 176 midwives and "health extension workers," 130 completed at 12 months follow-up. At baseline and after 6- and 12-months participants were assessed. Knowledge was tested by a Key Feature Questionnaire, skills by an Objective Structured Assessment of Technical Skills in a structured role-play scenario. RESULTS Baseline skills scores were low and comparable with a median of 12/100 in the intervention and the control group. After 6 months skills had doubled in the intervention group (adjusted mean difference 29.6; 95% CI 24.2-35.1 compared to 1·8; 95% CI - 2.7 to 6.3 in the control group). At 12 months skills had further improved in the intervention group (adjusted mean difference 13.3; 95% CI 8.3-18.3 compared to 3.1; 95% CI - 1.0 to 7.3 in the control group). Knowledge scores also significantly improved in the intervention group compared to the control (adjusted mean difference after 12 months 8.5; 95% CI 2.0-15.0). CONCLUSION The Safe Delivery App more than doubled clinical skills for managing postpartum haemorrhage among birth attendants making it an attractive tool to reduce maternal mortality. TRIAL REGISTRATION Clinicaltrial.gov Identifier NCT01945931. September 5, 2013. Maternal mortality caused by postpartum haemorrhage is a major public health concern in many low-income countries. Having access to skilled health care professionals during pregnancy and childbirth can prevent maternal deaths related to postpartum haemorrhage. mHealth interventions like the Safe Delivery App (SDA), a smartphone application, has shown the potential to improve the quality of care in emergency situations related to childbirth in low-income health system settings.This study examines the SDA as a training/education tool for improving health workers’ competencies and performances in managing postpartum haemorrhage. The SDA contained animated instruction videos on how to prevent and treat postpartum haemorrhage and a list of essential drugs and basic equipment.In Ethiopia, 70 health facilities and 176 birth attendants were included in a randomized controlled trial. The intervention group received a smartphone with the SDA installed and half a day of introduction to the use of the app. Birth attendants’ skills and knowledge in managing postpartum haemorrhage in the control and the intervention group were tested at baseline, 6 and 12 months after intervention.Our study found that the SDA is an effective tool to improve and sustain birth attendants’ knowledge and skills in the management of postpartum haemorrhage in a rural, low-resource health system setting in Ethiopia, which confirms findings in other non-randomized studies examining the SDA on the management of postpartum haemorrhage. eng
PICO Summary
Population
Midwives and health extension workers attending deliveries in 70 health facilities in Ethiopia (n= 176).
Intervention
Smartphone application ‘Safe Delivery App’ (SDA), (35 facilities, n= 87).
Comparison
No provision of the SDA (35 facilities, n= 89).
Outcome
The total scores in skills and knowledge tests for management of postpartum haemorrhage were the outcomes of this cluster randomised controlled trial. A total of 130 (74%) health workers completed the 6 and 12 months follow up, 65 in each arm, and were included in the analysis. Baseline skills scores were low and comparable with a median of 12/100 in the intervention and the control group. After 6 months skills had doubled in the intervention group (adjusted mean difference 29.6; 95% CI [24.2, 35.1] compared to 1.8; 95% CI [-2.7, 6.3] in the control group). At 12 months skills had further improved in the intervention group (adjusted mean difference 13.3; 95% CI [8.3, 18.3] compared to 3.1; 95% CI [-1.0, 7.3] in the control group). Knowledge scores also significantly improved in the intervention group compared to the control (adjusted mean difference after 12 months 8.5; 95% CI [2.0, 15.0]).
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Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery
Pacheco LD, Clifton RG, Saade GR, Weiner SJ, Parry S, Thorp JM Jr, Longo M, Salazar A, Dalton W, Tita ATN, et al
The New England journal of medicine. 2023;388(15):1365-1375
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Abstract
BACKGROUND Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).
PICO Summary
Population
Patients undergoing caesarean delivery at 31 U.S. hospitals (n= 11,000).
Intervention
Tranexamic acid (n= 5,529).
Comparison
Placebo (n= 5,471).
Outcome
The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days postpartum, whichever came first. A primary-outcome event occurred in 201 of 5,525 participants (3.6%) in the tranexamic acid group and in 233 of 5,470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% CI [0.74, 1.07]). Estimated intraoperative blood loss of more than 1 litre occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI [0.79, 1.05]). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI [0.82, 0.97]); the change in the haemoglobin level was -1.8 g per decilitre and -1.9 g per decilitre, respectively (mean difference, -0.1 g per decilitre; 95% CI [-0.2, -0.1]); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI [1.02, 1.61]). The frequencies of thromboembolic events and other adverse events were similar in the two groups.
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Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage
Gallos I, Devall A, Martin J, Middleton L, Beeson L, Galadanci H, Alwy Al-Beity F, Qureshi Z, Hofmeyr GJ, Moran N, et al
The New England journal of medicine. 2023
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Abstract
BACKGROUND Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).
PICO Summary
Population
Patients undergoing vaginal delivery enrolled in the E-MOTIVE cluster-randomised trial in 80 hospitals across Kenya, Nigeria, South Africa and Tanzania (n= 210,132).
Intervention
Multicomponent clinical intervention, including a calibrated blood-collection drape for early detection of postpartum haemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy, (intervention group, 40 hospitals).
Comparison
Usual care, estimating blood loss visually and using various interventions for postpartum haemorrhage in accordance with local or national guidelines, (usual-care group, 40 hospitals).
Outcome
The primary outcome was a composite of severe postpartum haemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval (CI), [0.32, 0.50]). Postpartum haemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI [1.41, 1.76]), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI [3.88, 6.28]).
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Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial
Ragni, M. V., Rothenberger, S. D., Feldman, R., Nance, D., Leavitt, A. D., Malec, L., Kulkarni, R., Sidonio, R., Jr., Kraut, E., Lasky, J., et al
The Lancet. Haematology. 2023
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Abstract
BACKGROUND Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. METHODS VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. FINDINGS Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). INTERPRETATION These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. FUNDING National Heart Lung Blood Institute (National Institutes of Health).
PICO Summary
Population
Patients aged 13-45 years with mild or moderate von Willebrand disease and heavy menstrual bleeding, enrolled in the VWDMin randomised crossover trial in 13 haemophilia treatment centres in the USA (n= 36).
Intervention
Recombinant von Willebrand factor (VWF) then tranexamic acid (n= 17).
Comparison
Tranexamic acid then recombinant VWF (n= 19).
Outcome
The trial was stopped early due to slow recruitment. Median follow-up was 23.97 weeks (IQR= 21.81, 28.14). The primary outcome was a 40-point reduction in pictorial blood assessment chart (PBAC) score by day 5 after two cycles of treatment. The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146; 95% CI [117, 199] vs. 213; [152, 298]; adjusted mean treatment difference 46; 95% CI [2, 90]). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs. zero during recombinant VWF treatment) and other bleeding (four [6%] vs. two [3%]).
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Randomized Controlled Trial Comparing Ferrous Sulfate and Iron Sucrose in Iron Deficiency Anemia in Pregnancy
Chauhan N, Dogra P, Sharma R, Kant S, Soni M
Cureus. 2023;15(2):e34858
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Editor's Choice
Abstract
INTRODUCTION Anemia among pregnant women is one of the major health concerns for healthcare workers. The management becomes a concern in the pregnancy where the question arises of which is better the intravenous iron sucrose or the oral ferrous sulfate tablets. To answer this, a randomized control trial comparing both the treatment options in a tertiary care government hospital was set up in the hilly terrains of India. This study discusses the effectiveness and practical aspect of using both, which seems to be the better out of both, and why. METHODS The study was conducted as a parallel-group, open-label randomized controlled trial (RCT) in the Department of Obstetrics and Gynecology of a tertiary care government hospital in India, with approximately 4,000 delivery loads annually. Ethical clearance was obtained from the institute's ethics committee (IEC), and the trial was registered with the Clinical Trial Registry of India (REF/2022/06/055013). Two hundred sixty-eight pregnant women between 18 and 45 years of age with moderate iron deficiency anemia (IDA) (hemoglobin (Hb) 7-9g/dl, microcytic-hypochromic, and serum ferritin <30ng/ml) were included in the study. Patients were randomly divided into two groups: group 1 with 134 patients to receive intravenous iron sucrose and group 2 with 134 patients to receive oral ferrous sulfate tablets. RESULTS The intravenous iron sucrose is superior in terms of tolerability and correction of iron deficiency anemia during pregnancy. CONCLUSION It yields a quicker rise in Hb and serum ferritin with no major side effects. In the difficult terrain of Himachal Pradesh, this makes IV iron sucrose a better option for anemic pregnant women who do not have easy access to health facilities resulting in a large number of them reaching hospitals with moderate to severe anemia at a later gestation.
PICO Summary
Population
Pregnant women with moderate iron deficiency anaemia (n= 268).
Intervention
Intravenous iron sucrose (n= 134).
Comparison
Oral ferrous sulfate tablets (n= 134).
Outcome
All women were followed up at four weeks after drug administration and at 36 weeks of gestation to check for the rise in serum ferritin and haemoglobin (Hb). The mean Hb after four weeks of therapy was 11.76 ± 1.29g/dl and 10.84 ± 0.67g/dl in the intravenous iron sucrose and oral ferrous sulfate group, respectively. The Hb at four weeks post-treatment was significantly higher in the intravenous group compared to the oral group. The mean Hb (g/dl) at 36 weeks of gestation was 12 ± 1.1g/dl and 11.28 ± 0.59g/dl in the intravenous iron sucrose and oral ferrous sulfate groups, respectively. The difference between the two groups was statistically significant. The rise in haemoglobin was 3.48g/dl and was significantly high in the intravenous iron sucrose group compared to the oral ferrous sulfate group which was 2.39g/dl after four weeks of treatment. The rise was 3.6g/dl and 2.82g/dl in the intravenous iron sucrose and oral ferrous sulfate group, respectively, at 36 weeks of gestation, and the difference was significant.
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Maternal anaemia and the risk of postpartum haemorrhage: a cohort analysis of data from the WOMAN-2 trial
The Lancet. Global health. 2023
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Editor's Choice
Abstract
BACKGROUND Worldwide, more than half a billion women of reproductive age are anaemic. Each year, about 70 000 women who give birth die from postpartum haemorrhage. Almost all deaths are in low-income or middle-income countries. We examined the association between anaemia and the risk of postpartum haemorrhage. METHODS We did a prospective cohort analysis of data from the World Maternal Antifibrinolytic-2 (WOMAN-2) trial. This trial enrols women with moderate or severe anaemia giving birth vaginally in hospitals in Pakistan, Nigeria, Tanzania, and Zambia. Hospitals in each country where anaemia in pregnancy is common were identified from a network established during previous obstetric trials. Women who were younger than 18 years without permission provided by a guardian, had a known tranexamic acid allergy, or developed postpartum haemorrhage before the umbilical cord was cut or clamped were excluded from the study. Prebirth haemoglobin, the exposure, was measured after hospital arrival and just before giving birth. Postpartum haemorrhage, the outcome, was defined in three ways: (1) clinical postpartum haemorrhage (estimated blood loss ≥500 mL or any blood loss sufficient to compromise haemodynamic stability); (2) WHO-defined postpartum haemorrhage (estimated blood loss of at least 500 mL); and (3) calculated postpartum haemorrhage (calculated estimated blood loss of ≥1000 mL). Calculated postpartum haemorrhage was estimated from the peripartum change in haemoglobin concentration and bodyweight. We used multivariable logistic regression to examine the association between haemoglobin and postpartum haemorrhage, adjusting for confounding factors. FINDINGS Of the 10 620 women recruited to the WOMAN-2 trial between Aug 24, 2019, and Nov 1, 2022, 10 561 (99·4%) had complete outcome data. 8751 (82·9%) of 10 561 women were recruited from hospitals in Pakistan, 837 (7·9%) from hospitals in Nigeria, 525 (5·0%) from hospitals in Tanzania, and 448 (4·2%) from hospitals in Zambia. The mean age was 27·1 years (SD 5·5) and mean prebirth haemoglobin was 80·7 g/L (11·8). Mean estimated blood loss was 301 mL (SD 183) for the 8791 (83·2%) women with moderate anaemia and 340 mL (288) for the 1770 (16·8%) women with severe anaemia. 742 (7·0%) women had clinical postpartum haemorrhage. The risk of clinical postpartum haemorrhage was 6·2% in women with moderate anaemia and 11·2% in women with severe anaemia. A 10 g/L reduction in prebirth haemoglobin increased the odds of clinical postpartum haemorrhage (adjusted odds ratio [aOR] 1·29 [95% CI 1·21-1·38]), WHO-defined postpartum haemorrhage (aOR 1·25 [1·16-1·36]), and calculated postpartum haemorrhage (aOR 1·23 [1·14-1·32]). 14 women died and 68 either died or had a near miss. Severe anaemia was associated with seven times higher odds of death or near miss (OR 7·25 [95% CI 4·45-11·80]) than was moderate anaemia. INTERPRETATION Anaemia is strongly associated with postpartum haemorrhage and the risk of death or near miss. Attention should be given to the prevention and treatment of anaemia in women of reproductive age. FUNDING The WOMAN-2 trial is funded by Wellcome and the Bill & Melinda Gates Foundation.
PICO Summary
Population
Women with moderate or severe anaemia giving birth vaginally in hospitals, enrolled in the WOMAN-2 trial in Pakistan, Nigeria, Tanzania, and Zambia (n= 10,620).
Intervention
This prospective cohort analysis of data from the WOMAN-2 trial examined the association between anaemia and the risk of postpartum haemorrhage.
Comparison
Outcome
Postpartum haemorrhage was defined in three ways: clinical postpartum haemorrhage; WHO-defined postpartum haemorrhage; and calculated postpartum haemorrhage. There was complete outcome data for 10,561 participants. Mean estimated blood loss was 301 mL (SD= 183) for the 8,791 (83.2%) women with moderate anaemia and 340 mL (288) for the 1,770 (16.8%) women with severe anaemia. 742 (7.0%) women had clinical postpartum haemorrhage. The risk of clinical postpartum haemorrhage was 6.2% in women with moderate anaemia and 11.2% in women with severe anaemia. A 10 g/L reduction in prebirth haemoglobin increased the odds of clinical postpartum haemorrhage (adjusted odds ratio (aOR)= 1.29; 95% CI [1.21, 1.38]), WHO-defined postpartum haemorrhage (aOR= 1.25; 95% CI [1.16, 1.36]), and calculated postpartum haemorrhage (aOR= 1.23; 95% CI [1.14, 1.32]). 14 women died and 68 either died or had a near miss. Severe anaemia was associated with seven times higher odds of death or near miss (OR= 7.25; 95% CI [4.45, 11.80]) than was moderate anaemia.
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LIBERTY Randomized Withdrawal Study: Relugolix Combination Therapy for Heavy Menstrual Bleeding Associated With Uterine Fibroids
Al-Hendy, A., Venturella, R., Arjona Ferreira, J. C., Li, Y., Soulban, G., Wagman, R. B., Lukes, A. S.
American journal of obstetrics and gynecology. 2023
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Editor's Choice
Abstract
BACKGROUND In the pivotal LIBERTY 1 and 2 trials and long-term extension (LTE) study, once-daily relugolix combination therapy (relugolix CT: relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) reduced menstrual blood loss (MBL) volume and pain in women with uterine fibroids (UF). Relugolix CT was well tolerated, with preservation of bone mineral density (BMD) through 52 weeks. OBJECTIVE To report the 2-year relugolix CT efficacy and safety results of the phase 3 LIBERTY randomized withdrawal study (RWS). STUDY DESIGN Women with UF-associated heavy menstrual bleeding (HMB) who completed the 24-week LIBERTY 1 or 2 trials followed by the 28-week LTE study (up to 52 weeks total treatment), and who met responder criteria (MBL volume <80 mL and ≥50% reduction from pivotal study baseline at week 48 (Week 24 of LTE) were randomized 1:1 to blinded treatment with relugolix CT or placebo for 52 weeks (total treatment period:104 weeks). For women who had a relapse of HMB during the study (MBL volume ≥80 mL), open-label relugolix CT was offered. Primary endpoint was the proportion of women who maintained MBL volume <80 mL through week 76 (Week 24 of RWS). Secondary endpoints included time to MBL volume ≥80 mL, proportion of women who maintained a MBL volume of <80 mL through week 104 (over the 52-week randomized treatment period), the proportion of women achieving or maintaining amenorrhea at week 76/end-of-treatment and change in UFS-Qol BPD and symptom severity scores. Analyses were performed in the modified intent-to-treat (mITT) population including all randomized women who received ≥1 dose of study drug. RESULTS Of the 229 randomized women (relugolix CT:115, placebo:114), 228 received study drug and 175 (76.7%) completed the RWS. Through week 76, 78.4% of women on relugolix CT maintained MBL volume <80 mL vs 15.1% in the placebo group difference of 63.4% [95%CI:52.9%-73.9%];p < 0.0001). At week 104, 69.8% of women on relugolix CT maintained MBL volume <80 mL vs 11.8% in the placebo group (difference of 58.0% [95%CI:47.0%-69.1%];p<0.0001 ). Through week 104, 88.3% of women on placebo relapsed with HMB (median time to relapse of 5.9 weeks). Among the 89 women in the placebo group who relapsed and received open-label rescue treatment, 87 women responded to relugolix CT, with an MBL volume <80 mL. The proportion of women who achieved or maintained amenorrhea were 57.4% vs 13.3% at week 76 (difference of 44.1% [95%CI:33.10%-55.1];p<0.0001) and 58.3% vs 10.6% at week 104 (difference 47.6% [95%CI:37.0%-58.3%];nominal p<0.0001) for relugolix CT and the placebo group, respectively. Relugolix CT was generally well tolerated; no new safety signals were identified, and the adverse event profile over the second year was consistent with that reported through the first year of treatment. BMD remained stable in women who received relugolix CT from week 52 to week 104. In women continuously treated with relugolix CT up to 2 years, BMD was generally preserved. CONCLUSIONS After 2 years of treatment with relugolix CT, there was evidence of durability of effect in maintaining low MBL volume in women with symptomatic UF. Most women had return of HMB and associated symptoms after treatment cessation, which improved upon retreatment with relugolix CT. Relugolix CT was well tolerated, the adverse event profile remained consistent and mean BMD was generally preserved through 2 years of treatment.
PICO Summary
Population
Women with uterine fibroid-associated heavy menstrual bleeding who completed the 24-week LIBERTY 1 or 2 trials (n= 229).
Intervention
Relugolix combination therapy (CT), (n= 115).
Comparison
Placebo (n= 114).
Outcome
The LIBERTY randomized withdrawal study was conducted to evaluate the 2-year relugolix CT efficacy and safety results. Relugolix CT was generally well tolerated; no new safety signals were identified, and the adverse event profile over the second year was consistent with that reported through the first year of treatment. Bone mineral density (BMD) remained stable in women who received relugolix CT from week 52 to week 104. In women continuously treated with relugolix CT up to 2 years, BMD was generally preserved.
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Placental Transfusion Strategies in Preterm Infants in Low- and Middle-Income Countries: A Systematic Review and Network Meta-Analysis
Ramaswamy VV, Bandyopadhyay T, Abiramalatha T, Shaik NB, Pullattayil SAk, Jasani B, Hegde V, Trevisanuto D, Weiner GM
Neonatology. 2022;:1-16
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Abstract
INTRODUCTION Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). METHODS Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. RESULTS Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30-60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78-1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01-1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). CONCLUSIONS In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival.
PICO Summary
Population
Preterm newborns in low- and middle-income countries (9 studies).
Intervention
Delayed cord clamping (DCC) for various time intervals.
Comparison
DCC until cord pulsations stop. Umbilical cord milking. Immediate cord clamping (ICC).
Outcome
Network meta-analysis of 9 randomised controlled trials could not rule out benefit or harm for survival from DCC 30-60s compared to ICC: relative risk (RR), (95% credible interval) 0.96 (0.78 to 1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01 to 1.22), very low certainty. Differences were not detected in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60s and 120s might improve the haematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty).
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9.
Intravenous oxytocin regimens in patients undergoing cesarean delivery: a systematic review and network meta-analysis of cluster-based groups
Tantry TP, Karanth H, Anniyappa S, Shetty PK, Upadya M, Shenoy SP, Kadam D
Journal of anesthesia. 2022
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Editor's Choice
Abstract
Information on evaluations of different oxytocin regimens used to prevent post-partum hemorrhage during cesarean delivery is scarce, and there is a lack of statistically pooled results for comparative doses. In this review, we aimed to analyze the effectiveness of different oxytocin regimens used and rank them accordingly. We performed a meta-analysis of randomized controlled trials (RCTs) reporting the incidence of additional uterotonic (AUT) use or amount of blood loss during cesarean delivery, where different oxytocin regimens were compared. Cluster analysis was used to define different clusters of oxytocin therapy based on the identified variable regimens. During the frequentist network meta-analysis, all clusters were compared to bolus clusters of dose range 3-5 IU. Data from 33 RCTs (6741 patients) to 26 RCTs (5422 patients) were assessed for AUT use and blood loss, respectively. Pairwise meta-analysis revealed a significant reduction in the use of AUTs or blood loss was recorded for bolus-infusion combination regimens. The network meta-analysis found that combined bolus-infusion regimens of (i) 3-5 IU and 0.25-1 IU/min or (ii) 3-5 IU and < 0.25 IU/min had statistically significant results for lowest consumption of AUTs (Ranks 1 and 2, respectively); whereas with the latter's use, the lowest blood loss (Rank 2) was observed. In contrast, the dose range, > 5 IU regimen was associated with higher side effects (lowest rank). During cesarean delivery, a significant reduction in the use of AUTs or blood loss (Rank 2) was recorded for bolus-infusion combination regimens. High doses did not have enough evidence to draw meaningful conclusions.
PICO Summary
Population
Patients undergoing cesarean delivery (37 studies, n= >7,000).
Intervention
Different intravenous oxytocin regimens (bolus, infusion, or a combination).
Comparison
Outcome
During the frequentist network meta-analysis, all clusters were compared to bolus clusters of dose range 3-5 IU. Data from 33 randomised controlled trials (RCTs), (6,741 patients) to 26 RCTs (5,422 patients) were assessed for additional uterotonic (AUT) use and blood loss, respectively. Pairwise meta-analysis revealed a significant reduction in the use of AUTs or blood loss was recorded for bolus-infusion combination regimens. The network meta-analysis found that combined bolus-infusion regimens of (i) 3-5 IU and 0.25-1 IU/min or (ii) 3-5 IU and < 0.25 IU/min had statistically significant results for lowest consumption of AUTs (Ranks 1 and 2, respectively); whereas with the latter's use, the lowest blood loss (Rank 2) was observed. In contrast, the dose range, > 5 IU regimen was associated with higher side effects (lowest rank). During cesarean delivery, a significant reduction in the use of AUTs or blood loss (Rank 2) was recorded for bolus-infusion combination regimens.
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10.
Tranexamic Acid for Prevention of Hemorrhage in Elective Repeat Cesarean Delivery - A Randomized Study
Ogunkua OT, Duryea EL, Nelson DB, Eddins MM, Klucsarits SE, McIntire DD, Leveno KJ
American journal of obstetrics & gynecology MFM. 2022;:100573
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Editor's Choice
Abstract
BACKGROUND The American College of Obstetricians and Gynecologists states that data is insufficient to recommend Tranexamic acid (TXA) prophylaxis for postpartum hemorrhage. OBJECTIVE This study's objective was to evaluate if prophylactic TXA reduces calculated blood loss versus placebo in women undergoing elective repeat cesarean delivery. STUDY DESIGN A double-blind, randomized, placebo-controlled trial, examining calculated blood loss with prophylactic doses of 1-gram of TXA given before skin incision and after placental delivery and standard uterotonics in women with singleton pregnancies at least 37 weeks' gestation, presenting for their second or third cesarean delivery under neuraxial anesthesia. The primary outcome was calculated blood loss at 24 hours. The calculation was based on the participant's height, weight, and the difference in hematocrit before the start of surgery and 24 hours after delivery. Prespecified secondary outcomes were quantification of maternal coagulation activity during the perioperative course. A sample size of 50 women per group was planned (N=100), based on a meta-analysis of mean reduction in blood loss after TXA. RESULTS 723 women were screened, and 110 women were randomized as follows: 55 to TXA and 55 to placebo. The primary outcome of mean calculated blood for TXA (2274 ± 469 mL) and the placebo group (2407 ± 388 mL), p > 0.05. In the secondary outcomes, D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL versus 4.3 ± 2.4 µg/mL), p < 0.001. CONCLUSIONS Prophylactic tranexamic acid did not decrease mean calculated blood loss. Significantly less participants had calculated blood loss greater than 2000 mL in the tranexamic acid group compared to the placebo group with lower levels of D-dimer at 24 hours.
PICO Summary
Population
Women undergoing elective repeat caesarean delivery (n= 110).
Intervention
Prophylactic doses of tranexamic acid (TXA) before skin incision and after placental delivery (n= 55).
Comparison
Standard uterotonics (n= 55).
Outcome
The mean calculated blood loss for TXA was 2,274 ± 469 mL, and for standard uterotonics was 2407 ± 388 mL. D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL vs. 4.3 ± 2.4 µg/mL).