Pub Date : 2024-07-24DOI: 10.1101/2024.07.24.24310793
Julia Wynn, Julio F Mateus Nino, Jenny Wigigins-Smith, J. Brett Bryant, J. Kriss Citty, J. Kyle Citty, Samir Ahuja, Roger Newman
Background: Approximately 15% of pregnant women in the US are RhD-negative. To prevent alloimmunization, current national guidelines endorse the administration of prophylactic anti-D immune globulin (RhIG) at 28 weeks of gestation and in any other episodes where alloimmunization can occur, such as bleeding, pregnancy loss, trauma or invasive procedures. Alloimmunization only occurs if the fetus is RhD-positive; however, 40% of RhD-negative mothers carry an RhD-negative fetus, resulting in, under the current guidelines, the sometimes repeated, use of unnecessary RhIG. Objective: We aimed to evaluate the performance of a next generation sequencing (NGS) with quantitative counting template (QCT) technology prenatal cell free DNA (cfDNA) assay in detecting the fetal RhD genotype in a diverse RhD-negative pregnant population in the United States (US). Study Design: This retrospective study was conducted in four US healthcare centers. The same NGS QCT cfDNA fetal RhD assay was offered to non-alloimmunized, RhD-negative pregnant individuals. Rh immune globulin (RhIG) was administered at the discretion of the provider. The assay's sensitivity, specificity, and accuracy were calculated considering the neonatal RhD serology results. Results: A total of 401 non-alloimunized RhD-negative pregnancies were included in the analysis. Fetal RhD was detected in 261 cases (65%), whereas it was negative in 140 (35%). The D antigen cfDNA result was 100% concordant with the neonatal serology, resulting in 100% sensitivity and positive predictive value and ( both 95% CI: 98.6%-100%) 100% specificity and negative predictive value (both 95% CI: 97.4%-100%). There were 10 pregnancies where the cfDNA analysis identified a non-RHD gene deletion, including RhDΨ (n=5) and RHD-CE-D hybrid variants (n=5). A total of 616 doses of RhIG were administered. Despite the fact that the study occurred prior to the current RhIG shortage and the recent American College (ACOG) advisory change, there was a marked decrease in the use of antenatal RhIG based on cfDNA results. This decrease was greater at certain sites and at later study periods. If the cfDNA results were fully utilized during the entire study period, up to 147 RhIG doses (24% of administered doses) could have been avoided, indicating the importance of guideline changes to support the use of cfDNA for fetal RhD detection to conserve this resource. Conclusion: This cfDNA analysis via NGS for detecting fetal RhD status is highly accurate with no false positive or false negative results in 401 racial and ethnically diverse pregnancies. Our data support implementing this assay for the routine management of non-alloimmunized RhD-negative individuals. This approach will result in more efficient and targeted prenatal care with administration of RhIG only when medically indicated.
{"title":"Clinical performance of cell free DNA for fetal RhD detection in RhD-negative pregnant individuals from the US population.","authors":"Julia Wynn, Julio F Mateus Nino, Jenny Wigigins-Smith, J. Brett Bryant, J. Kriss Citty, J. Kyle Citty, Samir Ahuja, Roger Newman","doi":"10.1101/2024.07.24.24310793","DOIUrl":"https://doi.org/10.1101/2024.07.24.24310793","url":null,"abstract":"Background: Approximately 15% of pregnant women in the US are RhD-negative. To prevent alloimmunization, current national guidelines endorse the administration of prophylactic anti-D immune globulin (RhIG) at 28 weeks of gestation and in any other episodes where alloimmunization can occur, such as bleeding, pregnancy loss, trauma or invasive procedures. Alloimmunization only occurs if the fetus is RhD-positive; however, 40% of RhD-negative mothers carry an RhD-negative fetus, resulting in, under the current guidelines, the sometimes repeated, use of unnecessary RhIG.\u0000Objective: We aimed to evaluate the performance of a next generation sequencing (NGS) with quantitative counting template (QCT) technology prenatal cell free DNA (cfDNA) assay in detecting the fetal RhD genotype in a diverse RhD-negative pregnant population in the United States (US). Study Design: This retrospective study was conducted in four US healthcare centers. The same NGS QCT cfDNA fetal RhD assay was offered to non-alloimmunized, RhD-negative pregnant individuals. Rh immune globulin (RhIG) was administered at the discretion of the provider. The assay's sensitivity, specificity, and accuracy were calculated considering the neonatal RhD serology results. Results: A total of 401 non-alloimunized RhD-negative pregnancies were included in the analysis. Fetal RhD was detected in 261 cases (65%), whereas it was negative in 140 (35%). The D antigen cfDNA result was 100% concordant with the neonatal serology, resulting in 100% sensitivity and positive predictive value and ( both 95% CI: 98.6%-100%) 100% specificity and negative predictive value (both 95% CI: 97.4%-100%). There were 10 pregnancies where the cfDNA analysis identified a non-RHD gene deletion, including RhDΨ (n=5) and RHD-CE-D hybrid variants (n=5). A total of 616 doses of RhIG were administered. Despite the fact that the study occurred prior to the current RhIG shortage and the recent American College (ACOG) advisory change, there was a marked decrease in the use of antenatal RhIG based on cfDNA results. This decrease was greater at certain sites and at later study periods. If the cfDNA results were fully utilized during the entire study period, up to 147 RhIG doses (24% of administered doses) could have been avoided, indicating the importance of guideline changes to support the use of cfDNA for fetal RhD detection to conserve this resource. Conclusion: This cfDNA analysis via NGS for detecting fetal RhD status is highly accurate with no false positive or false negative results in 401 racial and ethnically diverse pregnancies. Our data support implementing this assay for the routine management of non-alloimmunized RhD-negative individuals. This approach will result in more efficient and targeted prenatal care with administration of RhIG only when medically indicated.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141774170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1101/2024.07.09.24310137
Jessy Jindal, Francesco Dernie, David Launer, Georgia Richards
Coroners in England and Wales have a duty to write Prevention of Future Deaths (PFDs) reports when they believe that action should be taken to prevent similar deaths. We conducted a systematic case series of the reports involving maternal deaths to characterise the cases, causes of deaths, risk factors, concerns and organisational responses. The sample included all coroners PFDs published between July 2013 and 1 August 2023. There were 4435 reports at the time of data collection. A reproducible computer code developed from the Preventable Deaths Tracker was used to download all published PFDs from the Judiciary website. Reports were searched for keywords related to maternal deaths. Case information was extracted into pre-specified domains and compared to other data on maternal deaths. Twenty nine (29) reports involved a maternal death. The median age at death was 33.5 years (IQR 29-36 years) and 76% of deaths occurred in hospitals. The most common cause of death was haemorrhage. Coroners frequently voiced concerns around failure to provide appropriate treatment (57%), and failure of timely escalation (38%). Only 38% of PFDs received published responses from the organisations they were sent to, highlighting the underutilisation of these reports. When organisations did respond to the coroner, 80% reported that they implemented changes, including publishing new local policies, increasing training, or committing to increased staffing. PFDs highlighted gaps in obstetric care and national guidance which, if appropriately addressed, and regularly and routinely monitored, could prevent similar deaths.
{"title":"Preventable Maternal Deaths in England and Wales 2013–2023 – a systematic case series of coroners' reports","authors":"Jessy Jindal, Francesco Dernie, David Launer, Georgia Richards","doi":"10.1101/2024.07.09.24310137","DOIUrl":"https://doi.org/10.1101/2024.07.09.24310137","url":null,"abstract":"Coroners in England and Wales have a duty to write Prevention of Future Deaths (PFDs) reports when they believe that action should be taken to prevent similar deaths. We conducted a systematic case series of the reports involving maternal deaths to characterise the cases, causes of deaths, risk factors, concerns and organisational responses. The sample included all coroners PFDs published between July 2013 and 1 August 2023. There were 4435 reports at the time of data collection. A reproducible computer code developed from the Preventable Deaths Tracker was used to download all published PFDs from the Judiciary website. Reports were searched for keywords related to maternal deaths. Case information was extracted into pre-specified domains and compared to other data on maternal deaths. Twenty nine (29) reports involved a maternal death. The median age at death was 33.5 years (IQR 29-36 years) and 76% of deaths occurred in hospitals. The most common cause of death was haemorrhage. Coroners frequently voiced concerns around failure to provide appropriate treatment (57%), and failure of timely escalation (38%). Only 38% of PFDs received published responses from the organisations they were sent to, highlighting the underutilisation of these reports. When organisations did respond to the coroner, 80% reported that they implemented changes, including publishing new local policies, increasing training, or committing to increased staffing. PFDs highlighted gaps in obstetric care and national guidance which, if appropriately addressed, and regularly and routinely monitored, could prevent similar deaths.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"14 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141585229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.1101/2024.07.08.24309596
Chemtai Mungo, Katherine Sorgi, Cirillus Ogollah, Brenda Misiko, Cynthia Cheserem, George Githongo, Jackton Omoto
Cervical cancer remains a significant global health issue, especially in low- and middle-income countries (LMICs), where access to prevention and treatment is limited and women are at a higher risk of cervical cancer. Artesunate, a widely available drug used to treat malaria, has shown promise in treating human papillomavirus (HPV)-associated anogenital lesions including high-grade cervical precancer, in a recent Phase I studies in the United States. Data on the pharmacokinetics of artesunate following intravaginal use, and its implications on malaria resistance, are lacking. Objectives: The primary objective of this study is to investigate the pharmacokinetics of Artesunate (AS) and its active metabolite, dihydroartemisinin (DHA) following intravaginal use at the dosing and frequency intended for cervical precancer treatment. A secondary objective is to assess safety among study participants. Methods: We are conducting a single-arm, phase I trial with a sample size of 12 female volunteers. Participants will self-administer artesunate vaginal pessaries in the study clinic daily for 5 consecutive days. Participants will have their blood drawn prior to receiving the first dose of artesunate on day one of the study and then will receive 8 blood draws on study day five, prior to artesunate administration and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours after pessary administration. Pharmacokinetic parameters of artesunate and DHA will be calculated by way of quantitative analysis of with determination of maximum concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration versus time curve (AUC), apparent clearance, and elimination half-life (t1/2).
宫颈癌仍然是一个重大的全球健康问题，尤其是在中低收入国家（LMICs），这些国家的妇女获得预防和治疗的机会有限，患宫颈癌的风险较高。青蒿琥酯是一种广泛用于治疗疟疾的药物，最近在美国进行的一项 I 期研究显示，它有望治疗人乳头瘤病毒（HPV）相关的肛门病变，包括高级别宫颈癌前病变。目前尚缺乏阴道内使用青蒿琥酯的药代动力学数据及其对疟疾抗药性的影响。研究目的本研究的主要目的是调查青蒿琥酯（AS）及其活性代谢产物双氢青蒿素（DHA）在阴道内按照宫颈癌前病变治疗的剂量和频率使用后的药代动力学。次要目标是评估研究参与者的安全性。研究方法我们正在进行一项单臂 I 期试验，样本量为 12 名女性志愿者。参与者将每天在研究诊所自行使用青蒿琥酯阴道栓，连续使用 5 天。参与者将在研究第一天接受第一剂青蒿琥酯前抽血，然后在研究第五天接受 8 次抽血，分别在青蒿琥酯给药前、给药后 15 分钟、30 分钟、1 小时、2 小时、4 小时、6 小时和 8 小时进行。青蒿琥酯和 DHA 的药代动力学参数将通过定量分析进行计算，包括测定最大浓度（Cmax）、达到 Cmax 的时间（Tmax）、血浆浓度与时间曲线下面积（AUC）、表观清除率和消除半衰期（t1/2）。
{"title":"Phase I study on the pharmacokinetics of intravaginal, self-administered artesunate vaginal pessaries among women in Kenya.","authors":"Chemtai Mungo, Katherine Sorgi, Cirillus Ogollah, Brenda Misiko, Cynthia Cheserem, George Githongo, Jackton Omoto","doi":"10.1101/2024.07.08.24309596","DOIUrl":"https://doi.org/10.1101/2024.07.08.24309596","url":null,"abstract":"Cervical cancer remains a significant global health issue, especially in low- and middle-income countries (LMICs), where access to prevention and treatment is limited and women are at a higher risk of cervical cancer. Artesunate, a widely available drug used to treat malaria, has shown promise in treating human papillomavirus (HPV)-associated anogenital lesions including high-grade cervical precancer, in a recent Phase I studies in the United States. Data on the pharmacokinetics of artesunate following intravaginal use, and its implications on malaria resistance, are lacking. Objectives: The primary objective of this study is to investigate the pharmacokinetics of Artesunate (AS) and its active metabolite, dihydroartemisinin (DHA) following intravaginal use at the dosing and frequency intended for cervical precancer treatment. A secondary objective is to assess safety among study participants. Methods: We are conducting a single-arm, phase I trial with a sample size of 12 female volunteers. Participants will self-administer artesunate vaginal pessaries in the study clinic daily for 5 consecutive days. Participants will have their blood drawn prior to receiving the first dose of artesunate on day one of the study and then will receive 8 blood draws on study day five, prior to artesunate administration and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours after pessary administration. Pharmacokinetic parameters of artesunate and DHA will be calculated by way of quantitative analysis of with determination of maximum concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration versus time curve (AUC), apparent clearance, and elimination half-life (t1/2).","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Adverse pregnancy outcomes affect approximately 20% pregnant women, and their incidence is increasing. Objective: To investigate the effect of cardiovascular health during pregnancy on adverse pregnancy outcomes and the effect modification by psychological distress, social isolation, and income. Study Design: We analyzed data from 14,930 pregnant women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Cardiovascular health status during pregnancy was assessed using the eight components of Lifes Essential 8 as proposed by the American Heart Association, including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Adverse pregnancy outcomes were defined as composite outcomes of preeclampsia, gestational diabetes mellitus, preterm birth, and small for gestational age. Using logistic regression analyses, we examined the associations between cardiovascular health and adverse pregnancy outcomes, preeclampsia, gestational diabetes mellitus, preterm birth, small for gestational age, large for gestational age, low birth weight, and neonatal intensive care unit admission. Interactions with psychological distress, social isolation, and income were examined. Results: The numbers of participants with high, moderate, and low cardiovascular health status were 2,891 (19.4%), 11,498 (77.0%), and 541 (3.6%), respectively. Moderate and low cardiovascular health status were positively associated with adverse pregnancy outcomes (odds ratio and 95% confidence interval: 1.17 (10.04 to 1.32) and 2.64 (2.13 to 3.27), respectively). Low cardiovascular health status was also associated with a higher prevalence of preeclampsia, gestational diabetes mellitus, preterm birth, large for gestational age, and neonatal intensive care unit admission, and lower prevalence of small for gestational age. Among pregnant women with low cardiovascular health status, those who reported social isolation had a higher prevalence of adverse pregnancy outcomes than did those without social isolation (36.4% vs. 27.4%). However, this difference was attenuated for pregnant women with high cardiovascular health status (13.6% vs. 13.1%). Conclusions: Cardiovascular health status assessed using Lifes Essential 8 may be useful for assessing the risk of adverse pregnancy outcomes. Socially isolated pregnant women are more vulnerable to the effects of low cardiovascular health status; thus, they should be prioritized for access to primary care, lifestyle education, and appropriate pharmacotherapy.
{"title":"Synergistic effects of cardiovascular health and social isolation on adverse pregnancy outcomes","authors":"Hisashi Ohseto, Mami Ishikuro, Geng Chen, Ippei Takahashi, Genki Shinoda, Aoi Noda, Keiko Murakami, Masatsugu Orui, Noriyuki Iwama, Masahiro Kikuya, Hirohito Metoki, Atsushi Hozawa, Taku Obara, Shinichi Kuriyama","doi":"10.1101/2024.07.05.24309978","DOIUrl":"https://doi.org/10.1101/2024.07.05.24309978","url":null,"abstract":"Background: Adverse pregnancy outcomes affect approximately 20% pregnant women, and their incidence is increasing.\u0000Objective: To investigate the effect of cardiovascular health during pregnancy on adverse pregnancy outcomes and the effect modification by psychological distress, social isolation, and income.\u0000Study Design: We analyzed data from 14,930 pregnant women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Cardiovascular health status during pregnancy was assessed using the eight components of Lifes Essential 8 as proposed by the American Heart Association, including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Adverse pregnancy outcomes were defined as composite outcomes of preeclampsia, gestational diabetes mellitus, preterm birth, and small for gestational age. Using logistic regression analyses, we examined the associations between cardiovascular health and adverse pregnancy outcomes, preeclampsia, gestational diabetes mellitus, preterm birth, small for gestational age, large for gestational age, low birth weight, and neonatal intensive care unit admission. Interactions with psychological distress, social isolation, and income were examined.\u0000Results: The numbers of participants with high, moderate, and low cardiovascular health status were 2,891 (19.4%), 11,498 (77.0%), and 541 (3.6%), respectively. Moderate and low cardiovascular health status were positively associated with adverse pregnancy outcomes (odds ratio and 95% confidence interval: 1.17 (10.04 to 1.32) and 2.64 (2.13 to 3.27), respectively). Low cardiovascular health status was also associated with a higher prevalence of preeclampsia, gestational diabetes mellitus, preterm birth, large for gestational age, and neonatal intensive care unit admission, and lower prevalence of small for gestational age. Among pregnant women with low cardiovascular health status, those who reported social isolation had a higher prevalence of adverse pregnancy outcomes than did those without social isolation (36.4% vs. 27.4%). However, this difference was attenuated for pregnant women with high cardiovascular health status (13.6% vs. 13.1%). Conclusions: Cardiovascular health status assessed using Lifes Essential 8 may be useful for assessing the risk of adverse pregnancy outcomes. Socially isolated pregnant women are more vulnerable to the effects of low cardiovascular health status; thus, they should be prioritized for access to primary care, lifestyle education, and appropriate pharmacotherapy.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"366 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1101/2024.07.03.24309734
Rahul S Yerrabelli, Peggy K Palsgaard, Priya Shankarappa, Valerie Jennings
Objective: The majority of breech fetuses are delivered by Cesarean birth as few physicians are trained in vaginal breech birth. An external cephalic version (ECV) can prevent Cesarean delivery and the associated morbidity in these patients. Current guidelines recommend all patients with breech presentation be offered an ECV attempt. Not all attempts are successful, and an attempt does carry some risks so shared decision-making is necessary. To aid in patient counseling, over a dozen prediction models to predict ECV success have been proposed in the last few years. However, very few models have been externally validated, and thus none have been adopted into clinical practice. This study aims to use data from a United States hospital to provide further data on ECV prediction models. Study Design: This study retrospectively gathered data from Carle Foundation Hospital and used it to test six models previously proposed to predict ECV success. These models were Dahl 2021, Bilgory 2023, López Pérez 2020, Kok 2011, Burgos 2010, and Tasnim 2012 (GNK-PIMS score). Results: 125 patients undergoing 132 ECV attempts were included. 69 attempts were successful (52.2%). Dahl 2021 had the greatest predictive value (AUC 0.779), while Tasnim 2012 performed the worst (AUC 0.626). The remaining models had similar predictive values as each other (AUC 0.68-0.71). Bootstrapping confirmed that all models except Tasnim 2012 had confidence intervals not including 0.5. The bootstrapped 95% AUC confidence interval for Dahl 2021 was 0.71-0.84. In terms of calibration, Dahl 2021 was well calibrated with predicted probabilities matching observed probabilities. Bilgory 2023 and López Pérez were poorly calibrated. Conclusion: Multiple prediction tools have now been externally validated for ECV success. Dahl 2021 is the most promising prediction tool.
{"title":"The Optimal Prediction Model for Successful External Cephalic Version","authors":"Rahul S Yerrabelli, Peggy K Palsgaard, Priya Shankarappa, Valerie Jennings","doi":"10.1101/2024.07.03.24309734","DOIUrl":"https://doi.org/10.1101/2024.07.03.24309734","url":null,"abstract":"Objective: The majority of breech fetuses are delivered by Cesarean birth as few physicians are trained in vaginal breech birth. An external cephalic version (ECV) can prevent Cesarean delivery and the associated morbidity in these patients. Current guidelines recommend all patients with breech presentation be offered an ECV attempt. Not all attempts are successful, and an attempt does carry some risks so shared decision-making is necessary. To aid in patient counseling, over a dozen prediction models to predict ECV success have been proposed in the last few years. However, very few models have been externally validated, and thus none have been adopted into clinical practice. This study aims to use data from a United States hospital to provide further data on ECV prediction models. Study Design: This study retrospectively gathered data from Carle Foundation Hospital and used it to test six models previously proposed to predict ECV success. These models were Dahl 2021, Bilgory 2023, López Pérez 2020, Kok 2011, Burgos 2010, and Tasnim 2012 (GNK-PIMS score). Results: 125 patients undergoing 132 ECV attempts were included. 69 attempts were successful (52.2%). Dahl 2021 had the greatest predictive value (AUC 0.779), while Tasnim 2012 performed the worst (AUC 0.626). The remaining models had similar predictive values as each other (AUC 0.68-0.71). Bootstrapping confirmed that all models except Tasnim 2012 had confidence intervals not including 0.5. The bootstrapped 95% AUC confidence interval for Dahl 2021 was 0.71-0.84. In terms of calibration, Dahl 2021 was well calibrated with predicted probabilities matching observed probabilities. Bilgory 2023 and López Pérez were poorly calibrated. Conclusion: Multiple prediction tools have now been externally validated for ECV success. Dahl 2021 is the most promising prediction tool.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1101/2024.06.28.24309465
Tine Wroending, Kilian Vomstein, Kevin Delong, Agnete Troen Lundgaard, Sarah Mollerup, Brynjulf Mortensen, Elleke F. Bosma, Ann Marie Hellerung, Emilie Vester Engel, Klara Dortea Wiil, Julie Elm Heintz, Sofie Ingdam Halkjaer, Luisa W. Hugert, Tanja Schlaikjaer Hartwig, Andreas Munk Petersen, Anne Bloch Thomsen, David Westergaard, Nina La Cour Freiesleben, Henrik Westh, Johan E.T. van Hylckama, Laura Ensign, Henriette Svarre Nielsen
Here we describe the first double-blinded, randomized, placebo controlled trial (RCT) on vaginal microbiota transplantation (VMT) without antibiotics in women with both symptomatic and asymptomatic vaginal dysbiosis. Fortynine women were randomly assigned to VMT or placebo. The trial did not show a significant conversion to our predefined Lactobacillus-dominated microbiome. However, in participants not initially converting, antiseptic pretreatment before a subsequent VMT led to a 50% conversion rate, associated with an antiinflammatory shift in gene expression. Metagenomic sequencing and strain-level genetic analysis confirmed donor engraftment in five of 10 women who showed microbiome conversion. Extensive exploration of the microbiome, immune response and metadata revealed differences in baseline energy metabolism in participants who later experienced donor engraftment. Treatments for vaginal dysbiosis are urgently needed and given that VMT can lead to donor engraftment and change the vaginal immune profile, future studies should focus on optimizing this treatment for various womens health diseases.
{"title":"Vaginal Microbiota Transplantation (VMT) for treatment of vaginal dysbiosis without the use of antibiotics: A Double-Blinded Randomized Controlled Trial in healthy women with vaginal dysbiosis","authors":"Tine Wroending, Kilian Vomstein, Kevin Delong, Agnete Troen Lundgaard, Sarah Mollerup, Brynjulf Mortensen, Elleke F. Bosma, Ann Marie Hellerung, Emilie Vester Engel, Klara Dortea Wiil, Julie Elm Heintz, Sofie Ingdam Halkjaer, Luisa W. Hugert, Tanja Schlaikjaer Hartwig, Andreas Munk Petersen, Anne Bloch Thomsen, David Westergaard, Nina La Cour Freiesleben, Henrik Westh, Johan E.T. van Hylckama, Laura Ensign, Henriette Svarre Nielsen","doi":"10.1101/2024.06.28.24309465","DOIUrl":"https://doi.org/10.1101/2024.06.28.24309465","url":null,"abstract":"Here we describe the first double-blinded, randomized, placebo controlled trial (RCT) on vaginal microbiota transplantation (VMT) without antibiotics in women with both symptomatic and asymptomatic vaginal dysbiosis. Fortynine women were randomly assigned to VMT or placebo. The trial did not show a significant conversion to our predefined Lactobacillus-dominated microbiome. However, in participants not initially converting, antiseptic pretreatment before a subsequent VMT led to a 50% conversion rate, associated with an antiinflammatory shift in gene expression. Metagenomic sequencing and strain-level genetic analysis confirmed donor engraftment in five of 10 women who showed microbiome conversion. Extensive exploration of the microbiome, immune response and metadata revealed differences in baseline energy metabolism in participants who later experienced donor engraftment. Treatments for vaginal dysbiosis are urgently needed and given that VMT can lead to donor engraftment and change the vaginal immune profile, future studies should focus on optimizing this treatment for various womens health diseases.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Preterm premature rupture of membranes (PPROM) is associated with preterm delivery and neonatal complications. PPROM is often complicated by intra-amniotic inflammation and/or microbial invasion of the amniotic cavity with Ureaplasma or Mycoplasma. Various prophylactic antibiotic therapies have been proposed to prolong latency between PPROM and delivery, reduce the risk of clinical chorioamnionitis, and improve neonatal complications. However, information on the potential of azithromycin administration to reduce the microbial load of vaginal Ureaplasma and Mycoplasma remains lacking. This prospective cohort study included singleton pregnancies managed with prophylactic antibiotics for PPROM at less than 36 weeks of gestation. All patients received the standard antibiotic regimen for PPROM, which consisted of a single oral azithromycin and intravenous ampicillin every for 2 days followed by 5 days of oral amoxicillin. Vaginal swabs samples were collected when PPROM was confirmed and after the antibiotic regimen administration. The main outcome measures were to investigate the changes in vaginal Ureaplasma, Mycoplasma, and Lactobacillus spp. due to the antibiotic regimen. In addition, the association between the presence and changes in vaginal Ureaplasma and Mycoplasma, pregnancy outcomes, and neonatal complications were examined. Out of 82 eligible PPROM, 51 had positive vaginalUreaplasma. Thirty-six patients (52.2%) completed the antibiotic regimen. Among those with positive vaginal Ureaplasma who completed the antibiotic regimen, 75% experienced an increase in vaginal Ureaplasma levels. For those who delivered before completing all antibiotic doses, 40% had increased vaginal Ureaplasma levels. Furthermore, the antibiotic regimen resulted in decreased Lactobacillusspp. in almost all cases. However, vaginal Ureaplasma changes were not found to be associated with neonatal sepsis or bronchopulmonary dysplasia. This suggests that Ureaplasma became resistant to azithromycin. Future studies are needed to revalidate current antibiotic therapy for PPROM.
{"title":"Changes in vaginal Ureaplasma and Lactobacillus due to antibiotic regimen for premature rupture of membranes:","authors":"Haruna Kawaguchi, Yukiko Nakura, Ryo Yamamoto, Shusaku Hayashi, Makoto Takeuchi, Keisuke Ishii, Itaru Yanagihara","doi":"10.1101/2024.06.28.24309657","DOIUrl":"https://doi.org/10.1101/2024.06.28.24309657","url":null,"abstract":"Abstract Preterm premature rupture of membranes (PPROM) is associated with preterm delivery and neonatal complications. PPROM is often complicated by intra-amniotic inflammation and/or microbial invasion of the amniotic cavity with Ureaplasma or Mycoplasma. Various prophylactic antibiotic therapies have been proposed to prolong latency between PPROM and delivery, reduce the risk of clinical chorioamnionitis, and improve neonatal complications. However, information on the potential of azithromycin administration to reduce the microbial load of vaginal Ureaplasma and Mycoplasma remains lacking. This prospective cohort study included singleton pregnancies managed with prophylactic antibiotics for PPROM at less than 36 weeks of gestation. All patients received the standard antibiotic regimen for PPROM, which consisted of a single oral azithromycin and intravenous ampicillin every for 2 days followed by 5 days of oral amoxicillin. Vaginal swabs samples were collected when PPROM was confirmed and after the antibiotic regimen administration. The main outcome measures were to investigate the changes in vaginal Ureaplasma, Mycoplasma, and Lactobacillus spp. due to the antibiotic regimen. In addition, the association between the presence and changes in vaginal Ureaplasma and Mycoplasma, pregnancy outcomes, and neonatal complications were examined. Out of 82 eligible PPROM, 51 had positive vaginalUreaplasma. Thirty-six patients (52.2%) completed the antibiotic regimen. Among those with positive vaginal Ureaplasma who completed the antibiotic regimen, 75% experienced an increase in vaginal Ureaplasma levels. For those who delivered before completing all antibiotic doses, 40% had increased vaginal Ureaplasma levels. Furthermore, the antibiotic regimen resulted in decreased Lactobacillusspp. in almost all cases. However, vaginal Ureaplasma changes were not found to be associated with neonatal sepsis or bronchopulmonary dysplasia. This suggests that Ureaplasma became resistant to azithromycin. Future studies are needed to revalidate current antibiotic therapy for PPROM.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-30DOI: 10.1101/2024.06.28.24309652
Carey Elizabeth Gleason, N. Maritza Dowling, Firat Kara, Taryn T. James, Hector Salazar, Carola F. Simo, Sherman M. Harman, JoAnn E. Manson, Dustin B. Hammers, Frederick N. Naftolin, Lubna Pal, Virginia M. Miller, Marcelle I. Cedars, Rogerio A. Lobo, Michael Malek-Ahmadi, Kejal Kantarci
Background Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within three years of menopause onset. Long-term effects of mHT exposure during early postmenopause remain understudied. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS-Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that the participants randomized to one of two active estrogen formulations during early postmenopause would demonstrate differential longitudinal change in cognitive performance during the approximately ten years following randomization in the parent KEEPS trial when compared to women who received placebo. Specifically, transdermal estradiol (tE2) would demonstrate benefit over placebo, and oral conjugated equine estrogens (oCEE) demonstrate no effect compared to placebo. Methods and Findings The KEEPS-Cog was an ancillary study to the KEEPS, in which women were randomized to placebo or one of two forms of mHT, oCEE (Premarin, 0.45 mg/d) or tE2 (Climara, 50 µg/d) for 48 months. Micronized progesterone (Prometrium, 200 mg/d) was used by those in mHT arms. Approximately 10 years (M(SD)=9.57(1.08) years; range: 8-14 years) after randomization, women returned to repeat the original KEEPS-Cog test battery. Cognitive tests were analyzed as 4 factor scores and a global cognitive score. Because KEEPS-Continuation visits occurred 8-14 years post-randomization, linear latent growth models with distal outcomes tested whether cognitive performance at baseline in KEEPS and the change-in-cognition across KEEPS visits predicted “distal” KEEPS cognition, and whether mHT randomization of KEEPS modified this relationship. Covariates included education, age at continuation visit, and APOEe4 allele carrier status. All 727 postmenopausal participants in the KEEPS interventions were eligible for the KEEPS-Continuation. Among those participants, 622 (86%) had valid contact information and were invited to the study. Of these, 194 did not respond, 10 were deceased, and 119 declined to participate, resulting in 299 participants enrolled in the KEEPS-Continuation at seven sites. Of the 299 KEEPS-Continuation participants, 275 had cognitive data to estimate cognitive factors scores both at KEEPS and KEEPS-Continuation. Similar health characteristics were observed at KEEPS randomization for KEEPS-Continuation participants and nonparticipants (i.e. women not returning for the KEEPS-Continuation). Among the women enrolled in the KEEPS-Continuation, cognitive performance was not influenced by either mHT formulation employed in KEEPS. Models showed strong associations between baseline cognition and change-in-cognition during KEEPS and the same measures in KEEPS-Continuation, i.e
{"title":"Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study","authors":"Carey Elizabeth Gleason, N. Maritza Dowling, Firat Kara, Taryn T. James, Hector Salazar, Carola F. Simo, Sherman M. Harman, JoAnn E. Manson, Dustin B. Hammers, Frederick N. Naftolin, Lubna Pal, Virginia M. Miller, Marcelle I. Cedars, Rogerio A. Lobo, Michael Malek-Ahmadi, Kejal Kantarci","doi":"10.1101/2024.06.28.24309652","DOIUrl":"https://doi.org/10.1101/2024.06.28.24309652","url":null,"abstract":"Background\u0000Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within three years of menopause onset. Long-term effects of mHT exposure during early postmenopause remain understudied. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS-Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that the participants randomized to one of two active estrogen formulations during early postmenopause would demonstrate differential longitudinal change in cognitive performance during the approximately ten years following randomization in the parent KEEPS trial when compared to women who received placebo. Specifically, transdermal estradiol (tE2) would demonstrate benefit over placebo, and oral conjugated equine estrogens (oCEE) demonstrate no effect compared to placebo.\u0000Methods and Findings\u0000The KEEPS-Cog was an ancillary study to the KEEPS, in which women were randomized to placebo or one of two forms of mHT, oCEE (Premarin, 0.45 mg/d) or tE2 (Climara, 50 µg/d) for 48 months. Micronized progesterone (Prometrium, 200 mg/d) was used by those in mHT arms. Approximately 10 years (M(SD)=9.57(1.08) years; range: 8-14 years) after randomization, women returned to repeat the original KEEPS-Cog test battery. Cognitive tests were analyzed as 4 factor scores and a global cognitive score. Because KEEPS-Continuation visits occurred 8-14 years post-randomization, linear latent growth models with distal outcomes tested whether cognitive performance at baseline in KEEPS and the change-in-cognition across KEEPS visits predicted “distal” KEEPS cognition, and whether mHT randomization of KEEPS modified this relationship. Covariates included education, age at continuation visit, and APOEe4 allele carrier status.\u0000All 727 postmenopausal participants in the KEEPS interventions were eligible for the KEEPS-Continuation. Among those participants, 622 (86%) had valid contact information and were invited to the study. Of these, 194 did not respond, 10 were deceased, and 119 declined to participate, resulting in 299 participants enrolled in the KEEPS-Continuation at seven sites. Of the 299 KEEPS-Continuation participants, 275 had cognitive data to estimate cognitive factors scores both at KEEPS and KEEPS-Continuation. Similar health characteristics were observed at KEEPS randomization for KEEPS-Continuation participants and nonparticipants (i.e. women not returning for the KEEPS-Continuation).\u0000Among the women enrolled in the KEEPS-Continuation, cognitive performance was not influenced by either mHT formulation employed in KEEPS. Models showed strong associations between baseline cognition and change-in-cognition during KEEPS and the same measures in KEEPS-Continuation, i.e","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1101/2024.06.28.24309381
Georgina Constantinou, Rebecca Webb, Susan Ayers, Eleanor J Mitchell, Jane Daniels
Background: The risks and benefits of maternal screening for GBS during pregnancy or the intrapartum period are widely debated, since screen positive results trigger prophylactic antibiotic use. There is little known about womens and health professionals views regarding GBS screening. Objectives: To conduct a rapid review to synthesise evidence on women and health professionals: (1) knowledge and awareness of; (2) preferences for; and (3) acceptability of GBS screening programmes, and (4) how feasible they are to implement. Method: Literature searches were conducted using online databases from their inception to 2023. Papers were included if they reported primary research from the perspectives of health professionals and women, about their knowledge and awareness, preferences, acceptability and feasibility of different types of GBS screening programmes. Data were assessed for confidence using GRADE-CERQual and analysed using a convergent synthesis approach. Findings: 42 papers were eligible for inclusion. A total of 16,306 women and professionals were included. Women generally did not have extensive knowledge about GBS. Health professionals had a higher level of knowledge than women. Women were generally (but not universally) positive about GBS testing procedures. Some women were concerned about the impact on their place of birth. Discussion and Conclusion: Where GBS screening programmes are available, parents must be provided with high quality information about them. Health professionals and service managers need to weigh up the benefits and risks of screening for GBS with local feasibility and treatment options, and with womens individual values and birth plans.
{"title":"Acceptability and feasibility of maternal screening for Group B Streptococcus: a rapid review.","authors":"Georgina Constantinou, Rebecca Webb, Susan Ayers, Eleanor J Mitchell, Jane Daniels","doi":"10.1101/2024.06.28.24309381","DOIUrl":"https://doi.org/10.1101/2024.06.28.24309381","url":null,"abstract":"Background: The risks and benefits of maternal screening for GBS during pregnancy or the intrapartum period are widely debated, since screen positive results trigger prophylactic antibiotic use. There is little known about womens and health professionals views regarding GBS screening. Objectives: To conduct a rapid review to synthesise evidence on women and health professionals: (1) knowledge and awareness of; (2) preferences for; and (3) acceptability of GBS screening programmes, and (4) how feasible they are to implement.\u0000Method: Literature searches were conducted using online databases from their inception to 2023. Papers were included if they reported primary research from the perspectives of health professionals and women, about their knowledge and awareness, preferences, acceptability and feasibility of different types of GBS screening programmes. Data were assessed for confidence using GRADE-CERQual and analysed using a convergent synthesis approach. Findings: 42 papers were eligible for inclusion. A total of 16,306 women and professionals were included. Women generally did not have extensive knowledge about GBS. Health professionals had a higher level of knowledge than women. Women were generally (but not universally) positive about GBS testing procedures. Some women were concerned about the impact on their place of birth. Discussion and Conclusion: Where GBS screening programmes are available, parents must be provided with high quality information about them. Health professionals and service managers need to weigh up the benefits and risks of screening for GBS with local feasibility and treatment options, and with womens individual values and birth plans.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1101/2024.06.27.24309586
Chemtai Mungo, Katherine Sorgi, Caroline Hoch, Jennifer Tang, Lisa Rahangdale, Jackton Omoto
Background: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer. Methods: This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Discussion: Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women.
背景：宫颈癌对中低收入国家（LMICs）妇女的影响尤为严重，90%的死亡病例发生在这些国家。目前的宫颈癌前病变治疗依赖于医护人员，而他们对许多妇女来说可能是遥不可及的。开发一种由患者控制的宫颈癌前病变治疗方法可以大大改善偏远地区的就医条件，促进宫颈癌的二级预防：这是一项在肯尼亚 18 名 HIV 阳性和 HIV 阴性妇女中进行的 I 期试验，目的是调查青蒿琥酯阴道栓剂在宫颈癌前病变筛查阳性并需要切除治疗的妇女中的应用情况。首要目标是自行服用青蒿琥酯阴道栓的安全性。参与者将每天从阴道自行注射 200 毫克青蒿琥酯，连续 5 天，之后一周不用药，共重复 4 个周期（第 1、3、5、7 周自行注射青蒿琥酯）。包括参与者随访在内的总研究时间为 48 周。在治疗阶段，将通过查看症状日记和每两周一次的随访来评估安全性和依从性。数据分析将包括定量和定性方法：考虑到在医疗条件有限的低收入国家采用切除术治疗宫颈癌前病变所面临的挑战，本研究提出了一种使用阴道内青蒿琥酯的替代方法。这项临床试验将提供重要的安全性和有效性数据，说明如何将青蒿琥酯作为局部疗法用于艾滋病病毒阳性和阴性妇女。
{"title":"Intravaginal artesunate pessaries for treatment of cervical intraepithelial neoplasia 2/3 among HIV-positive and HIV-negative women in Kenya: Study protocol for a pilot trial","authors":"Chemtai Mungo, Katherine Sorgi, Caroline Hoch, Jennifer Tang, Lisa Rahangdale, Jackton Omoto","doi":"10.1101/2024.06.27.24309586","DOIUrl":"https://doi.org/10.1101/2024.06.27.24309586","url":null,"abstract":"Background: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer.\u0000Methods: This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods.\u0000Discussion: Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women.","PeriodicalId":501409,"journal":{"name":"medRxiv - Obstetrics and Gynecology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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