Integrative transcriptomics and proteomics analyses to reveal the therapeutic effect and mechanism of Buxue Yimu Pills in medical-induced incomplete abortion rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medical abortions using mifepristone and misoprostol have been approved in many countries for early pregnancy loss. Despite its high success rate, this medication regimen can result in incomplete abortion, which is responsible for endometrial damage, prolonged uterine bleeding, abdominal pain, etc. Buxue Yimu Pills (BYP) is a famous Chinese medicine prescription that is widely used in the field of gynecology and obstetrics for treating patients with postpartum complications. However, the therapeutic effect and mechanism of BYP remain to be explored. AIM OF THE STUDY: This study aimed to clarify the therapeutic effect and mechanism of action of BYP in postpartum complications using mifepristone and misoprostol-induced incomplete abortion in rats. MATERIALS AND METHODS: Experimental medical-induced incomplete abortion model rats were constructed using mifepristone and misoprostol, and further treated with saline or BYP by intragastric administration. Detailed information regarding the changes in mRNA and protein levels in the uterine tissues of rats regulated by BYP was illustrated by RNA sequencing (RNA-seq) analysis and quantitative proteomics analysis. The differentially expressed genes and proteins were further subjected to Gene Ontology (GO) and pathway enrichment analyses and further verified using quantitative Real-time PCR (qRT-PCR) analysis and western blot assay. RESULTS: BYP administration markedly alleviated the increase in serum prostaglandin F2α (PGF2α) and expression of PGF2α receptor (PGF2αR) in uterine tissues and inhibited the decrease in serum chorionic gonadotrophin (CG). Compared with the model group, 674 genes were upregulated and 344 genes were downregulated by BYP administration; 108 proteins were upregulated and 48 proteins were downregulated by BYP administration. qRT-PCR analysis of the uterine tissues showed that BYP treatment reversed the variation tendency of genes, including Mmp7, Mmp14, Timp2, Col6a4, Jak2, Wnt7a, and Mylk compared with the model group. Western blot analysis showed that BYP administration affected PKCδ, Collagen VI, MMP7, TIMP2, MLCK, and p-MLC protein levels. CONCLUSION: BYP administration facilitated uterine recovery in medical-induced incomplete abortion rats, and this therapeutic effect involved various targets and biological processes, including the TIMP2/MMP7 and MLCK/p-MLC signaling pathways, etc.

Evaluating women's acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians: a mixed methods study.

BACKGROUND: Studies evaluating task sharing in postabortion care have mainly focused on women in first trimester and many lack a qualitative component. We aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences in Uganda. METHODS: Our mixed methods study combined 1140 structured interview data from a randomized controlled equivalence trial and in-depth interviews (n = 28) among women managed with misoprostol for second trimester incomplete abortion at 14 public health facilities in Uganda. Acceptability, our main outcome, was measured at the 14-day follow-up visit using a structured questionnaire as a composite variable of: 1) treatment experience (as expected/ better than expected/ worse than expected), and 2) satisfaction - if patient would recommend the treatment to a friend or choose the method again. We used generalized mixed effects models to obtain the risk difference in acceptable post abortion care between midwife and physician groups. We used inductive content analysis for qualitative data. RESULTS: From 14th August 2018 to 16th November 2021, we assessed 7190 women for eligibility and randomized 1191 (593 to midwife and 598 to physician). We successfully followed up 1140 women and 1071 (94%) found the treatment acceptable. The adjusted risk difference was 1.2% (95% CI, - 1.2 to 3.6%) between the two groups, and within our predefined equivalence range of - 5 to + 5%. Treatment success and feeling calm and safe after treatment enhanced acceptability while experience of side effects and worrying bleeding patterns reduced satisfaction. CONCLUSIONS: Misoprostol treatment of uncomplicated second trimester incomplete abortion was equally and highly acceptable to women when care was provided by midwives compared with physicians. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to postabortion care services. TRIAL REGISTRATION: ClinicalTrials.gov NCT03622073.

Approximately 9.6% of abortion-related deaths occur in Sub-Saharan Africa. These deaths can be prevented if unintended pregnancies are avoided, women can access safe abortions within the expectations of the country's laws, and post abortion care (PAC) services are provided equitably. Previous research shows that women with abortion complications in the first trimester of pregnancy can be treated with misoprostol by either midwives or physicians. This sharing of tasks between the midwives and physicians is safe, effective, and acceptable. However, there is a gap in evidence on task sharing in the second trimester. To check practicability of task sharing in second trimester, we aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients' lived treatment experiences. Our study therefore combined quantitative and qualitative approaches. Women's acceptability of misoprostol treatment for incomplete second trimester abortion was found to be equally acceptable when provided by midwives compared with physicians. Treatment success, feeling calm and safe after treatment increased acceptability, while experience of side effects and worrying bleeding patterns reduced satisfaction. Counselling of women may address some of these problems since it provides reassurance and reduces anxiety. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient's access to PAC services.

Comparison of the effectiveness and safety of treatment of incomplete second trimester abortion with misoprostol provided by midwives and physicians: a randomised, controlled, equivalence trial in Uganda.

BACKGROUND: To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of treatment for incomplete second trimester abortion with misoprostol, comparing care provision by midwives with that provided by physicians in Uganda. METHODS: Our multicentre, randomised, controlled, equivalence trial undertaken in 14 health facilities in Uganda recruited women with incomplete abortion of uterine size 13-18 weeks. We randomly assigned (1:1) women to clinical assessment and treatment by either midwife or physician. The randomisation sequence was computer generated, in blocks of four to 12, and stratified for study site. Participants received sublingual misoprostol (400 µg once every 3 h for up to five doses). The study was not concealed from the health-care providers and study participants. Primary outcome was complete abortion within 24 h that did not require surgical evacuation. Analysis was per-protocol and intention to treat; the intention-to-treat population consisted of women who were randomised, received at least one dose of misoprostol, and reported primary outcome data, and the per-protocol population excluded women with unexplained discontinuation of treatment. We used generalised mixed-effects models to obtain the risk difference. The predefined equivalence range was -5% to 5%. The trial was registered at ClinicalTrials.gov, NCT03622073. FINDINGS: Between Aug 14, 2018, and Nov 16, 2021, 1191 eligible women were randomly assigned to each group (593 women to the midwife group and 598 to the physician group). 1164 women were included in the per-protocol analysis, and 530 (92%) of 577 women in the midwife group and 553 (94%) of 587 women in the physician group had a complete abortion within 24 h. The model-based risk difference for the midwife versus physician group was -2·3% (95% CI -4·4 to -0·3), and within our predefined equivalence range (-5% to 5%). Two women in the midwife group received blood transfusion. INTERPRETATION: Clinical assessment and treatment of second trimester incomplete abortion with misoprostol provided by midwives was equally effective and safe as when provided by physicians. In low-income settings, inclusion of midwives in the medical management of uncomplicated second trimester incomplete abortion has potential to increase women's access to safe post-abortion care. FUNDING: Swedish Research Council and THRiVE-2.

"I'll just deal with this on my own": a qualitative exploration of experiences with self-managed abortion in the United States.

BACKGROUND: A growing body of evidence indicates that some people seek options to terminate a pregnancy without medical assistance, but experiences doing so have largely been documented only among people accessing a clinic-based abortion. We aim to describe self-managed abortion (SMA) experiences of people recruited outside of clinics, including their motivations for SMA, pregnancy confirmation and decision-making processes, method choices, and clinical outcomes. METHODS: In 2017, we conducted 14 in-depth interviews with self-identified females of reproductive age who recently reported in an online survey administered to Ipsos' KnowledgePanel that, since 2000, they had attempted SMA while living in the United States. We asked participants about their reproductive histories, experiences seeking reproductive health care, and SMA experiences. We used an iterative process to develop codes and analyzed transcripts using thematic content analysis methods. RESULTS: Motivations and perceptions of effectiveness varied by whether participants had confirmed the pregnancy prior to SMA. Participants who confirmed their pregnancies chose SMA because it was convenient, accessible, and private. Those who did not test for pregnancy were motivated by a preference for autonomy and felt empowered by the ability to try something on their own before seeking facility-based care. Participants prioritized methods that were safe and available, though not always effective. Most used herbs or over-the-counter medications; none used self-sourced abortion medications, mifepristone and/or misoprostol. Five participants obtained facility-based abortions and one participant decided to continue the pregnancy after attempting SMA. The remaining eight reported being no longer pregnant after SMA. None of the participants sought care for  SMA complications; one participant saw a provider to confirm abortion completion. CONCLUSIONS: There are many types of SMA experiences. In addition to those who pursue SMA as a last resort (after facing barriers to facility-based care) or as a first resort (because they prefer homeopathic remedies), our findings show that some individuals view SMA as a potential interim step worth trying after suspecting pregnancy and before accessing facility-based care. These people in particular would benefit from a medication abortion product available over the counter, online, or in the form of a missed-period pill.

Some people in the United States (US) attempt to end a pregnancy on their own without medical supervision. What we know about this experience comes from studies focused on people who go to clinics. In this study, we conducted 14 interviews with self-identified women ages 18­49 who recently reported attempting to end a pregnancy on their own and who were recruited outside of the clinic setting. We asked participants about their fertility histories, experiences seeking reproductive health care, and experiences ending a pregnancy without medical assistance. Those who took a pregnancy test and then chose to end the pregnancy on their own did so because it was convenient, accessible, and private. Those who did not test for pregnancy felt empowered by the ability to try something on their own before seeking facility-based care. All participants prioritized methods that were safe and available, though not always effective. After they attempted to end the pregnancy on their own, five participants accessed abortion care in facilities, one decided to continue the pregnancy, and eight were no longer pregnant. Our findings show that, in addition to people who end a pregnancy on their own as a last resort (after facing barriers to facility-based care) or as a first resort (because of preferences for homeopathic methods), a third group values having an interim step to try after suspecting pregnancy and before accessing facility-based care. These people would particularly benefit from a medication abortion product available over the counter, online, or in the form of a missed-period pill.

Evaluation and ranking of different interventions for pain relief during outpatient hysteroscopy: A systematic review and network meta-analysis.

AIM: To identify the highest-ranked pharmacological and nonpharmacological interventions for pain relief during outpatient hysteroscopy. METHODS: We conducted an online bibliographic search in different databases from inception till July 2019. We included randomized controlled trials assessing effect of pharmacological and nonpharmacological interventions on pain relief during outpatient hysteroscopy. Our main outcomes were pain scores at different endpoints of the procedure. We applied this network meta-analysis based on the frequentist approach using statistical package 'netmeta' (version 1.0-1) in R. RESULTS: The review included 39 randomized controlled trials (Women n = 3964). Misoprostol plus intracervical block anesthesia (mean difference [MD] = -3.32, 95% confidence interval [CI] [-6.06, -0.59]), misoprostol (MD = -1.92, 95% CI [-3.04, -0.81]) and IV analgesia (MD = -2.01, 95% CI [-3.27, -0.25]) were effective in reducing pain during the procedure compared to placebo. Ranking probability showed that misoprostol plus intracervical block anesthesia was the highest ranked pharmacological treatment for pain relief during the procedure (P score = 0.92) followed by misoprostol alone (P score = 0.78), and IV analgesia (P score = 0.76). Regarding nonpharmacological treatments, transcutaneous electrical nerve stimulation (TENS) showed a significant pain reduction compared to placebo (MD = -1.80, 95% CI [-3.31, -0.29]). TENS ranked as the best nonpharmacological treatment (P score = 0.80) followed by CO2 distention (P score = 0.65) and bladder distention (P score = 0.60). CONCLUSION: Combination of misoprostol plus local anesthesia appears to be the most effective pharmacological approach for pain reduction during and after outpatient hysteroscopy. Nonpharmacological approaches as TENS and bladder distention showed considerable efficacy but should be further investigated.

The Quality of Postabortion Care in Tanzania: Service Provider Perspectives and Results From a Service Readiness Assessment.

INTRODUCTION: In 2015, the government of Tanzania launched an effort to strengthen the quality of postabortion care (PAC), an integrated health service that includes treatment for abortion complications and provision of family planning counseling and voluntary services, in 25 facilities in mainland Tanzania and in Zanzibar. METHODS: To help guide the government's initiative, we conducted a mixed-method study in 2016 using health facility surveys and in-depth interviews with health care workers that offer PAC. Surveys of the 25 facilities assessed the current use of services and readiness to deliver them. Provider performance in PAC was assessed through direct observation of client-provider interactions. In-depth interviews (IDIs) with 30 staff from the facilities provided qualitative information on priorities for PAC quality improvement. RESULTS: In the 6 months preceding the study, 2,175 PAC clients sought care at the facilities. Of these PAC clients, 55% chose a family planning method, of whom 6% chose a voluntary long-acting reversible contraceptive. The median facility PAC readiness scores were 45% for health centers, 49% for district hospitals, and 61% for regional referral hospitals. Direct observations of manual vacuum aspiration provision for PAC revealed that providers implemented, on average, 69% of the critical clinical steps. For misoprostol provision, PAC providers implemented, on average, 42% of the critical steps. Multilevel influences affected PAC providers' work, often adversely, by shaping their confidence in their technical competency, confusing their role as health care workers and as clients' peers, and coloring their attitudes toward clientele. The PAC providers also felt that their ability to implement their responsibilities was shaped by lapses in essential support and functionality of the health care system, as well as by social and cultural norms. CONCLUSIONS: Technical assistance approaches that blend training, clinical quality improvement, systems strengthening, and social interventions that address demand-side barriers are needed to ensure providers achieve their potential and are able to deliver high-quality PAC.

Evaluating the safety, effectiveness and acceptability of treatment of incomplete second-trimester abortion using misoprostol provided by midwives compared with physicians: study protocol for a randomized controlled equivalence trial.

BACKGROUND: A large proportion of abortion-related mortality and morbidity occurs in the second trimester of pregnancy. The Uganda Ministry of Health policy restricts management of second-trimester incomplete abortion to physicians who are few and unequally distributed, with most practicing in urban regions. Unsafe and outdated methods like sharp curettage are frequently used. Medical management of second-trimester post-abortion care by midwives offers an advantage given the difficulty in providing surgical management in low-income settings and current health worker shortages. The study aims to assess the safety, effectiveness and acceptability of treatment of incomplete second-trimester abortion using misoprostol provided by midwives compared with physicians. METHODS: A randomized controlled equivalence trial implemented at eight hospitals and health centers in Central Uganda will include 1192 eligible women with incomplete abortion of uterine size > 12 weeks up to 18 weeks. Each participant will be randomly assigned to undergo a clinical assessment and treatment by either a midwife (intervention arm) or a physician (control arm). Enrolled participants will receive 400 µg misoprostol administered sublingually every 3 h up to five doses within 24 h at the health facility until a complete abortion is confirmed. Women who do not achieve complete abortion within 24 h will undergo surgical uterine evacuation. Pre discharge, participants will receive contraceptive counseling and information on what to expect in terms of side effects and signs of complications, with follow-up 14 days later to assess secondary outcomes. Analyses will be by intention to treat. Background characteristics and outcomes will be presented using descriptive statistics. Differences between groups will be analyzed using risk difference (95% confidence interval) and equivalence established if this lies between the predefined range of - 5% and + 5%. Chi-square tests will be used for comparison of outcome and t tests used to compare mean values. P ≤ 0.05 will be considered statistically significant. DISCUSSION: Our study will provide evidence to inform national and international policies, standard care guidelines and training program curricula on treatment of second-trimester incomplete abortion for improved access. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03622073 . Registered on 9 August 2018.

Scaling Up Misoprostol to Prevent Postpartum Hemorrhage at Home Births in Mozambique: A Case Study Applying the ExpandNet/WHO Framework.

BACKGROUND: Mozambique has a high maternal mortality ratio, and postpartum hemorrhage (PPH) is a leading cause of maternal deaths. In 2015, the Mozambican Ministry of Health (MOH) commenced a program to distribute misoprostol at the community level in selected districts as a strategy to reduce PPH. This case study uses the ExpandNet/World Health Organization (WHO) scale-up framework to examine the planning, management, and outcomes of the early expansion phase of the scale-up of misoprostol for the prevention of PPH in 2 provinces in Mozambique. METHODS: Qualitative semistructured interviews were conducted between February and October 2017 in 5 participating districts in 2 provinces. Participants included program stakeholders, health staff, community health workers (CHWs), and traditional birth attendants (TBAs). Interviews were analyzed using the ExpandNet/WHO framework alongside national policy and planning documents and notes from a 2017 national Ministry of Health maternal, newborn, and child health workshop. Outcomes were estimated using misoprostol coverage and access in 2017 for both provinces. RESULTS: The study revealed a number of barriers and facilitators to scale-up. Facilitators included a supportive political and legal environment; a clear, credible, and relevant innovation; early expansion into some Ministry of Health systems and a strong network of CHWs and TBAs. Barriers included a reduction in reach due to a shift from universal distribution to application of eligibility criteria; fear of misdirecting misoprostol for abortion or labor induction; limited communication and understanding of the national PPH prevention strategy; inadequate monitoring and evaluation; challenges with logistics systems; and the inability to engage remote TBAs. Lower coverage was found in Inhambane province than Nampula province, possibly due to NGO support and political champions. CONCLUSION: This study identified the need for a formal review of the misoprostol program to identify adaptations and to develop a systematic scale-up strategy to guide national scale-up.

'Nausicaa' compression suture: a simple and effective alternative to hysterectomy in placenta accreta spectrum and other causes of severe postpartum haemorrhage.

Postpartum haemorrhage (PPH), especially resulting from placenta accreta spectrum (PAS), has become a worldwide concern in maternity care. We describe a novel method of uterine compression sutures (the 'Nausicaa' technique) as an alternative to hysterectomy for patients who have suffered from major PPH. We applied this technique in 68 patients with major PPH during caesarean section (including 43 patients with PAS, 20 patients with placenta praevia totalis, and five patients with uterine atony), and none of these patients required further hysterectomy. We conclude that our Nausicaa suture is a simple and feasible alternative to hysterectomy in patients suffering from major PPH.

Tecnologias de cuidado para prevenção e controle da hemorragia no terceiro estágio do parto: revisão sistemática / Care technologies to prevent and control hemorrhage in the third stage of labor: a systematic review / Tecnologías de cuidado para prevención y control de la hemorragia en la tercera etapa del parto: revisión sistemática

Objetivo identificar evidências acerca das contribuições das tecnologias de cuidado usadas para prevenção e controle da hemorragia no terceiro estágio do parto. Método revisão sistemática com busca em bases de dados. Dois investigadores selecionaram os textos de forma independente na primeira etapa e, na segunda, em reunião de conciliação. Para avaliação da concordância, aplicou-se o coeficiente Kappa; para avaliação do risco de viés e classificação dos níveis de evidência, adotou-se o Grading of Recommendations, Assessment, Development and Evaluation. Resultados incluíram-se 42 artigos; desses, 34 classificados como tecnologias de produto, sendo a maioria produtos farmacológicos; dois referentes ao uso do saco plástico transparente para a coleta de sangue e contribuição do intervalo de nascimento e dos cuidados pré-natais. Os oito artigos classificados como tecnologias de processo se referiam a manejo ativo do terceiro estágio do parto, tração controlada de cordão, massagem uterina e intervenções educacionais. Conclusão as tecnologias de produto e de processo apresentaram evidência alta e moderada confirmada em 61,90% dos artigos. Os níveis de evidência demonstram contribuições das tecnologias para prevenção e controle da hemorragia. Na prática clínica, o enfermeiro deve oferecer cuidados à mulher fundamentados em evidências científicas e construir protocolos sobre as ações de cuidado da enfermagem.

Objective to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor. Method systematic review with database searches. First, two researchers independently selected the papers and, at a second point in time, held a reconciliation meeting. The Kappa coefficient was used to assess agreement, while the Grading of Recommendations, Assessment, Development and Evaluation was adopted to assess risk of bias and classify level of evidence. Results in this review, 42 papers were included, 34 of which addressed product technologies, most referred to pharmacological products, while two papers addressed the use of blood transparent plastic bags collector and the contribution of birth spacing and prenatal care. The eight papers addressing process technologies included the active management of the third stage of labor, controlled cord traction, uterine massage, and educational interventions. Conclusion product and process technologies presented high and moderate evidence confirmed in 61.90% of the papers. The levels of evidence confirm the contribution of technologies to prevent and control hemorrhaging. Clinical nurses should provide scientific-based care and develop protocols addressing nursing care actions.

Objetivo identificar las evidencias acerca de las contribuciones de las tecnologías de cuidado usadas para la prevención y el control de la hemorragia en la tercera etapa del parto. Método revisión sistemática con búsqueda en bases de datos. Dos investigadores seleccionaron los textos, de forma independiente, en la primera etapa; y, en la segunda en reunión de conciliación. Para evaluación de la concordancia fue aplicado el coeficiente Kappa; para evaluación del riesgo de sesgo y clasificación de los niveles de evidencia, se adoptó el Grading of Recommendations, Assessment, Development and Evaluation. Resultados fueron incluidos 42 artículos; de estos, 34 fueron clasificados como: tecnologías de producto (siendo la mayoría productos farmacológicos), dos referentes a la contribución del saco plástico transparente recolector de sangre y del intervalo de nacimiento y de los cuidados prenatales. Los ocho artículos clasificados como tecnologías de proceso se referían al manejo activo de la tercera etapa del parto, a la tracción controlada del cordón, al masaje uterino y a intervenciones educacionales. Conclusión las tecnologías de producto y de proceso presentaron evidencia alta y moderada, lo que fue confirmado en 61,90% de los artículos. Los niveles de evidencia demuestran las contribuciones de las tecnologías para la prevención y el control de la hemorragia. En la práctica clínica, el enfermero debe ofrecer cuidados a la mujer fundamentados en evidencias científicas y construir protocolos sobre las acciones de cuidado de la enfermería.

Castor oil for induction of labour: a retrospective study.

PURPOSE: The aim of this study is to investigate the safety and efficacy of castor oil to induce labour. MATERIALS AND METHODS: A retrospective observational case control study was conducted over five years. Castor oil was proposed to women referred to the Birth Centre (Castor Oil group (COG)). They were compared to women who chose to be followed by the traditional doctor-led unit (control group (CG)). Castor oil was administered in a 60 ml single dose in 200 ml of warm water. Inclusion criteria were gestational age between 40 and 41 weeks plus premature rupture of membranes between 12 and 18 hours or amniotic fluid index ≤4 or Bishop Score of ≤4 or absence of spontaneous labour over 41 + 4 weeks. RESULTS: Pharmacological induction of labour was required for 18 women in the COG (45%) and 36 in the CG (90%) (p < .001). The mode of delivery differed significantly between groups: women assuming castor oil showed a higher incidence of vaginal delivery, whereas the incidence of caesarean section was lower in the COG, but no statistical significance was reached. CONCLUSIONS: The use of castor oil is related to a higher probability of labour initiation within 24 hours. Castor oil can be considered a safe non-pharmacological method for labour induction.

Post-abortion care with misoprostol - equally effective, safe and accepted when administered by midwives compared to physicians: a randomised controlled equivalence trial in a low-resource setting in Kenya.

OBJECTIVE: To assess the effectiveness of midwives administering misoprostol to women with incomplete abortion seeking post-abortion care (PAC), compared with physicians. DESIGN: A multicentre randomised controlled equivalence trial. The study was not masked. SETTINGS: Gynaecological departments in two hospitals in a low-resource setting, Kenya. POPULATION: Women (n=1094) with incomplete abortion in the first trimester, seeking PAC between 1 June 2013 to 31 May 2016. Participants were randomly assigned to receive treatment from midwives or physicians. 409 and 401 women in the midwife and physician groups, respectively, were included in the per-protocol analysis. INTERVENTIONS: 600 µg misoprostol orally, and contraceptive counselling by a physician or midwife. MAIN OUTCOME MEASURES: Complete abortion not needing surgical intervention within 7-10 days. The main outcome was analysed on the per-protocol population with a generalised estimating equation model. The predefined equivalence range was -4% to 4%. Secondary outcomes were analysed descriptively. RESULTS: The proportion of complete abortion was 94.8% (768/810): 390 (95.4%) in the midwife group and 378 (94.3%) in the physician group. The proportion of incomplete abortion was 5.2% (42/810), similarly distributed between midwives and physicians. The model-based risk difference for midwives versus physicians was 1.0% (-4.1 to 2.2). Most women felt safe (97%; 779/799), and 93% (748/801) perceived the treatment as expected/easier than expected. After contraceptive counselling the uptake of a contraceptive method after 7-10 days occurred in 76% (613/810). No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol provided by midwives is equally effective, safe and accepted by women as when administered by physicians in a low-resource setting. Systematically provided contraceptive counselling in PAC is effective to mitigate unmet need for contraception. TRIAL REGISTRATION NUMBER: NCT01865136; Results.

Prevention of postpartum haemorrhage by community-based auxiliary midwives in hard-to-reach areas of Myanmar: a qualitative inquiry into acceptability and feasibility of task shifting.

BACKGROUND: In Myanmar, postpartum haemorrhage is the leading cause of maternal mortality and contributes to around 30% of all maternal deaths. The World Health Organization recommends training and supporting auxiliary midwives to administer oral misoprostol for prevention of postpartum haemorrhage in resource-limited settings. However, use of misoprostol by auxiliary midwives has not formally been approved in Myanmar. Our study aimed to explore community and provider perspectives on the roles of auxiliary midwives and community-level provision of oral misoprostol by auxiliary midwives. METHODS: A qualitative inquiry was conducted in Ngape Township, Myanmar. A total of 15 focus group discussions with midwives, auxiliary midwives, community members and mothers with children under the age of three were conducted. Ten key informant interviews were performed with national, district and township level health planners and implementers of maternal and child health services. All audio recordings were transcribed verbatim in Myanmar language. Transcripts of focus group discussions were fully translated into English before coding, while key informants' data were coded in Myanmar language. Thematic analysis was done using ATLAS.ti software. RESULTS: Home births are common and auxiliary midwives were perceived as an essential care provider during childbirth in hard-to-reach areas. Main reasons provided were that auxiliary midwives are more accessible than midwives, live in the hard-to-reach areas, and are integrated in the community and well connected with midwives. Auxiliary midwives generally reported that their training involved instruction on active management of the third stage of labour, including use of misoprostol, but not all auxiliary midwives reported using misoprostol in practice. Supportive reasons for task-shifting administration of oral misoprostol to auxiliary midwives included discussions around the good relationship and trust between auxiliary midwives and midwives, whereby midwives felt confident distributing misoprostol to auxiliary midwives. However, the lack of clear government-level written permission to distribute the drug was perceived as a barrier to task shifting. CONCLUSION: This study highlights the acceptability of misoprostol use by auxiliary midwives to prevent postpartum haemorrhage, and findings suggest that it should be considered as a promising intervention for task shifting in Myanmar.

Implementing at-scale, community-based distribution of misoprostol tablets to mothers in the third stage of labor for the prevention of postpartum haemorrhage in Sokoto State, Nigeria: Early results and lessons learned.

BACKGROUND: Postpartum haemorrhage (PPH) is a leading cause of maternal death in Sokoto State, Nigeria, where 95% of women give birth outside of a health facility. Although pilot schemes have demonstrated the value of community-based distribution of misoprostol for the prevention of PPH, none have provided practical insight on taking such programs to scale. METHODS: A community-based system for the distribution of misoprostol tablets (in 600ug) and chlorhexidine digluconate gel 7.1% to mother-newborn dyads was introduced by state government officials and community leaders throughout Sokoto State in April 2013, with the potential to reach an estimated 190,467 annual births. A simple outcome form that collected distribution and consumption data was used to assess the percentage of mothers that received misoprostol at labor through December 2014. Mothers' conditions were tracked through 6 weeks postpartum. Verbal autopsies were conducted on associated maternal deaths. RESULTS: Misoprostol distribution was successfully introduced and reached mothers in labor in all 244 wards in Sokoto State. Community data collection systems were successfully operational in all 244 wards with reliable capacity to record maternal deaths. 70,982 women or 22% of expected births received misoprostol from April 2013 to December 2014. Between April and December 2013, 33 women (< 1%) reported that heavy bleeding persisted after misoprostol use and were promptly referred. There were a total of 11 deaths in the 2013 cohort which were confirmed as maternal deaths by verbal autopsies. Between January and December of 2014, a total 434 women (1.25%) that ingested misoprostol reported associated side effects. CONCLUSION: It is feasible and safe to utilize government guidelines on results-based primary health care to successfully introduce community distribution of life saving misoprostol at scale to reduce PPH and improve maternal outcomes. Lessons from Sokoto State's at-scale program implementation, to assure every mother's right to uterotonics, can inform scale-up elsewhere in Nigeria.

Healthcare providers' knowledge and practices associated with postpartum hemorrhage during facility delivery in Dar es Salaam, Tanzania.

OBJECTIVE: To investigate healthcare providers' knowledge and practices associated with prevention and management of postpartum hemorrhage (PPH) to improve care in urban settings and reduce maternal morbidity and mortality. METHODS: As part of a cross-sectional, survey-based study, providers from 14 government health facilities providing maternal delivery services in the Ilala Municipality, Dar es Salaam, Tanzania, were surveyed about PPH-related practices and knowledge in April 2015. The data were analyzed descriptively, and χ2 tests of independence were used to examine relationships between experience, facility type, and knowledge. RESULTS: Among 115 respondents, 7 (6.1%) answered all PPH knowledge questions correctly. The mean knowledge score was 63.9%±21.1%. Non-calibrated methods for estimating postpartum blood loss were common; only 62 (53.9%) respondents reported direct collection. Referral of patients for PPH-related transfer was reported by 49 (42.6%) respondents; transportation and finances were barriers to transfer. Respondents requested continued training and additional supplies to address emergencies. CONCLUSION: Healthcare providers had suboptimal knowledge of PPH risk factors, diagnosis, and causes. Strategies that provide ongoing education and equip lower-level facilities with adequate supplies might minimize PPH-related transfers. Providing prenatal women with basic delivery items (e.g. a blood collection device) and misoprostol is a viable option to ensure that essential PPH-prevention tools are available at delivery.

Preventing deaths due to haemorrhage.

Prevention of deaths from obstetric haemorrhage requires effective health systems including family planning, commodities, personnel, infrastructure and ultimately universal access to comprehensive obstetric care for women giving birth. The main causes of death associated with antepartum haemorrhage are placental abruption, placenta praevia and uterine rupture. Preventive measures include preconceptual folate supplementation, management of hypertensive disorders, early diagnosis of placenta praevia and use of uterine stimulants cautiously, particularly misoprostol. Preventive measures for post-partum haemorrhage include routine active management of the third stage of labour. Treatment involves a cascade of increasingly invasive interventions in rapid sequence until the bleeding is stopped. These interventions include fluid resuscitation, removal of the placenta, bimanual uterine compression, uterotonics, tranexamic acid, suturing of lower genital tract injury, blood product replacement, balloon tamponade, laparotomy, stepwise uterine devascularization, uterine compression sutures and hysterectomy. Emergency temporizing measures include application of the non-pneumatic anti-shock garment, and at laparotomy, aortic compression and uterine tourniquet application. The effectiveness of treatment methods and the optimal dosage of misoprostol are research priorities. Interesting new approaches include transvaginal uterine artery clamping and suction uterine tamponade.

Knowledge, acceptability, and use of misoprostol for preventing postpartum hemorrhage following home births in rural Ethiopia.

OBJECTIVE: To assess knowledge of, and intentions to use misoprostol to preventing postpartum hemorrhage by women in a pastoralist community of the Somali Region of Ethiopia. METHODS: A cross-sectional study enrolled women aged 15-49years living in Adadle district, Ethiopia, between April 26 and May 3, 2012. A structured questionnaire was used to collect data on participants' knowledge of misoprostol and if they had any intention to use it in the future. Participants also detailed their preferred healthcare provider for administering misoprostol. RESULTS: A total of 829 women were enrolled in the study. Among the participants, 42 (5.1%) had knowledge of misoprostol and 302 (36.4%) described themselves as being willing to use misoprostol in the future. Among respondents who were willing to use misoprostol in the future, traditional birth attendants were the preferred healthcare practitioners to administer it. CONCLUSION: Awareness of misoprostol was low in the study sample but willingness to use the drug was somewhat higher. Raising awareness and knowledge among communities and traditional birth attendants regarding the advantages of misoprostol is crucial to enhance uptake and reduce the incidence of postpartum hemorrhage.

Misoprostol for Prevention of Postpartum Hemorrhage at Home Birth in Afghanistan: Program Expansion Experience.

INTRODUCTION: Afghanistan has a maternal mortality ratio of 400 per 100,000 live births. Hemorrhage is the leading cause of maternal death. Two-thirds of births occur at home. A pilot program conducted from 2005 to 2007 demonstrated the effectiveness of using community health workers for advance distribution of misoprostol to pregnant women for self-administration immediately following birth to prevent postpartum hemorrhage. The Ministry of Public Health requested an expansion of the pilot to study implementation on a larger scale before adopting the intervention as national policy. The purpose of this before-and-after study was to determine the effectiveness of advance distribution of misoprostol for self-administration across 20 districts in Afghanistan and identify any adverse events that occurred during expansion. METHODS: Cross-sectional household surveys were conducted pre- (n = 408) and postintervention (n = 408) to assess the effect of the program on uterotonic use among women who had recently given birth. Maternal death audits and verbal autopsies were conducted to investigate peripartum maternal deaths that occurred during implementation in the 20 districts. RESULTS: Uterotonic use among women in the sample increased from 50.3% preintervention to 74.3% postintervention. Because of a large-scale investment in Afghanistan in training and deployment of community midwives, it was assumed that all women who gave birth in facilities received a uterotonic. A significant difference in uterotonic use at home births was observed among women who lived farthest from a health facility (> 90 minutes self-reported travel time) compared to women who lived closer (88.5% vs 38.9%; P < .0001). All women who accepted misoprostol and gave birth at home used the drug. No maternal deaths were identified among those women who used misoprostol. DISCUSSION: The results of this study build on the findings of the pilot program and provide evidence on the effectiveness, primarily measured by uterotonic use, of an expansion of advance distribution of misoprostol for self-administration.

Women's Acceptability of Misoprostol Treatment for Incomplete Abortion by Midwives and Physicians - Secondary Outcome Analysis from a Randomized Controlled Equivalence Trial at District Level in Uganda.

OBJECTIVE: This study aimed to assess women´s acceptability of diagnosis and treatment of incomplete abortion with misoprostol by midwives, compared with physicians. METHODS: This was an analysis of secondary outcomes from a multi-centre randomized controlled equivalence trial at district level in Uganda. Women with first trimester incomplete abortion were randomly allocated to clinical assessment and treatment with misoprostol by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and stratified for health care facility. Acceptability was measured in expectations and satisfaction at a follow up visit 14-28 days following treatment. Analysis of women's overall acceptability was done using a generalized linear mixed-effects model with an equivalence range of -4% to 4%. The study was not masked. The trial is registered at ClinicalTrials.org, NCT 01844024. RESULTS: From April 2013 to June 2014, 1108 women were assessed for eligibility of which 1010 were randomized (506 to midwife and 504 to physician). 953 women were successfully followed up and included in the acceptability analysis. 95% (904) of the participants found the treatment satisfactory and overall acceptability was found to be equivalent between the two study groups. Treatment failure, not feeling calm and safe following treatment, experiencing severe abdominal pain or heavy bleeding following treatment, were significantly associated with non-satisfaction. No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol by midwives and physician was highly, and equally, acceptable to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01844024.

A postpartum haemorrhage package with condom uterine balloon tamponade: a prospective multi-centre case series in Kenya, Sierra Leone, Senegal, and Nepal.

OBJECTIVE: To evaluate the effectiveness and safety of an ultra-low-cost uterine balloon tamponade package (ESM-UBT™) for facility-based management of uncontrolled postpartum haemorrhage (PPH) in Kenya, Sierra Leone, Senegal, and Nepal. DESIGN: Prospective multi-centre case series. SETTING: Facilities in resource-scarce areas of Kenya, Sierra Leone, Nepal, and Senegal. POPULATION: Women with uncontrolled postpartum haemorrhage in 307 facilities across the four countries. METHODS: A standardised ESM-UBT package was implemented in 307 facilities over 29 months (1 September 2012 to 1 February 2015). Data were collected via a multi-pronged approach including data card completion, chart reviews, and provider interviews. Beginning in August 2014, women who had previously undergone UBT placement were sought and queried regarding potential complications associated with UBT use. MAIN OUTCOME MEASURES: All-cause survival, survival from PPH, and post-UBT use complications (surgery, hospitalisation, antibiotics for pelvic infection) associated with UBT use. RESULTS: 201 UBTs were placed for uncontrolled vaginal haemorrhage refractory to all other interventions. In all, 38% (71/188) of women were either unconscious or confused at the time of UBT insertion. All-cause survival was 95% (190/201). However, 98% (160/163) of women survived uncontrolled PPH if delivery occurred at an ESM-UBT online facility. One (1/151) potential UBT-associated complication (postpartum endometritis) was identified and two improvised UBTs were placed in women with a ruptured uterus. CONCLUSIONS: These pilot data suggest that the ESM-UBT package is a clinically promising and safe method to arrest uncontrolled postpartum haemorrhage and save women's lives. The UBT was successfully placed by all levels of facility-based providers. Future studies are needed to further evaluate the effectiveness of ESM-UBT in low-resource settings. TWEETABLE ABSTRACT: Evidence for ESM-UBT as a clinically promising and safe method to arrest uncontrolled PPH and save women's lives.