Prophylactic tranexamic acid for reducing intraoperative blood loss during cesarean section in women at high risk of postpartum hemorrhage: A double-blind placebo randomized controlled trial.

BACKGROUND: Postpartum hemorrhage remains a leading cause of maternal mortality especially in developing countries. The majority of previous trials on the effectiveness of tranexamic acid in reducing blood loss were performed in low-risk women for postpartum hemorrhage. A recent Cochrane Systematic Review recommended that further research was needed to determine the effects of prophylactic tranexamic acid for preventing intraoperative blood loss in women at high risk of postpartum hemorrhage. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of tranexamic acid in reducing intraoperative blood loss when given prior to cesarean delivery in women at high risk of postpartum hemorrhage. STUDY DESIGN: The study is a double-blind randomized controlled trial. METHODS: The study consisted of 200 term pregnant women and high-risk preterm pregnancies scheduled for lower-segment cesarean delivery at Enugu State University of Science and Technology, Teaching Hospital, Parklane, Enugu, Nigeria. The participants were randomized into two arms (intravenous 1 g of tranexamic acid or placebo) in a ratio of 1:1. The participants received either 1 g of tranexamic acid or placebo (20 mL of normal saline) intravenously at least 10 min prior to commencement of the surgery. The primary outcome measures were the mean intraoperative blood loss and hematocrit change 48 h postoperatively. RESULTS: The baseline sociodemographic characteristics were similar in both groups. The tranexamic acid group when compared to the placebo group showed significantly lower mean blood loss (442.94 ± 200.97 versus 801.28 ± 258.68 mL; p = 0.001), higher mean postoperative hemoglobin (10.39 + 0.96 versus 9.67 ± 0.86 g/dL; p = 0.001), lower incidence of postpartum hemorrhage (1.0% versus 19.0%; p = 0.001), and lower need for use of additional uterotonic agents after routine management of the third stage of labor (39.0% versus 68.0%; p = 0.001), respectively. However, there was no significant difference in the mean preoperative hemoglobin (11.24 ± 0.88 versus 11.15 ± 0.90 g/dL; p = 0.457), need for other surgical intervention for postpartum hemorrhage (p > 0.05), and reported side effect, respectively, between the two groups. CONCLUSION: Prophylactic administration of tranexamic acid significantly decreases postpartum blood loss, improves postpartum hemoglobin, decreases the need for additional uterotonics, and prevents postpartum hemorrhage following cesarean section in pregnant women at high risk of postpartum hemorrhage. Its routine use during cesarean section in high-risk women may be encouraged.The trial was registered in the Pan-African Clinical Trial Registry with approval number PACTR202107872851363.

Antivirals for prevention of hepatitis B virus mother-to-child transmission in human immunodeficiency virus positive pregnant women co-infected with hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV)-human Immunodeficiency virus (HIV) co-infection promotes an aggressive disease course of HBV infection. In the only available non-Cochrane systematic review on antiviral therapy during pregnancy for prevention of mother-to-child transmission of HBV, none of the women studied had HBV-HIV co-infection but were either HBV- or HIV-seropositive. Treatment of HBV alone may develop HIV-strains that are resistant to non-nucleoside reverse transcriptase inhibitors. Accordingly, co-treatment of the HIV infection is recommended. OBJECTIVES: To evaluate the benefits and harms of tenofovir-based antiviral combination regimens versus placebo, tenofovir alone, or non-tenofovir-based antiviral regimen either alone or in combination with HBV for the prevention of mother-to-child transmission of HBV in HIV-positive pregnant women co-infected with HBV. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS (Bireme), Science Citation Index Expanded (Web of Science), and Conference Proceedings Citation Index-Science (Web of Science) on 30 January 2023. We manually searched the reference lists of included trials, searched on-line trial registries, and contacted experts in the field and pharmaceutical companies for any further potential trials. SELECTION CRITERIA: We aimed to include randomised clinical trials comparing tenofovir-based antiviral combination regimens (anti-HIV regimen with lopinavir-ritonavir therapy, or any other antiviral therapy, and two drugs with activity against HBV, specifically, tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), plus lamivudine or emtricitabine) with placebo alone, or tenofovir alone, or non-tenofovir-based antiviral regimen (zidovudine, lamivudine, telbivudine, emtricitabine, entecavir, lopinavir-ritonavir, or any other antiviral therapy) either alone or in combination with at least two other antivirals. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes included all-cause infant mortality, proportion of infants with serious adverse events, proportion of infants with HBV mother-to-child transmission, all-cause maternal mortality, and proportion of mothers with serious adverse events. Secondary outcomes included proportion of infants with adverse events not considered serious, proportion of mothers with detectable HBV DNA (deoxyribonucleic acid) (before delivery), maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. We used RevMan Web to carry out analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CIs). We performed sensitivity analysis. We assessed risk of bias using predefined domains, assessed the certainty of the evidence using GRADE, controlled risk of random errors with Trial Sequential Analysis, and presented outcome results in a summary of findings table. MAIN RESULTS: Five completed trials were included, of which four trials contributed data to one or more of the outcomes. They included a total of 533 participants randomised to tenofovir-based antiviral combination regimens (196 participants) versus control (337 participants). The control groups received non-tenofovir-based antiviral regimens either as zidovudine alone (three trials) or as a combination of zidovudine, lamivudine and lopinavir-ritonavir (five trials). None of the trials used placebo or tenofovir alone. All trials were at unclear risk of bias. Four trials used intention-to-treat analyses. In the remaining trial, two participants in the intervention group and two in the control group were lost to follow-up. However, the outcomes of these four participants were not described. Tenofovir-based antiviral combination regimen versus control We are very uncertain about the effect of a tenofovir-based antiviral combination regimen versus control on all-cause infant mortality (RR 2.24, 95% CI 0.72 to 6.96; participants = 132; trials = 1; very low-certainty evidence); proportion of infants with serious adverse events (RR 1.76, 95% CI 1.27 to 2.43; participants = 132; trials = 1; very low-certainty evidence), and proportion of mothers with serious adverse events (RR 0.90, 95% CI 0.62 to 1.32; participants = 262; trials = 2; very low-certainty evidence). No trial reported data on the proportion of infants with HBV mother-to-child transmission and all-cause maternal mortality. We are also very uncertain about the effect of tenofovir-based antiviral combination regimens versus control on the proportion of infants with adverse events not considered serious (RR 0.94, 95% CI 0.06 to 13.68; participants = 31; trials = 1; very low-certainty evidence), and proportion of mothers with detectable HBV DNA (before delivery) (RR 0.66, 95% CI 0.42 to 1.02; participants = 169; trials = 2; very low-certainty evidence). No trial reported data on maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. All trials received support from industry. AUTHORS' CONCLUSIONS: We do not know what the effects of tenofovir-based antiviral combination regimens are on all-cause infant mortality, proportion of infants with serious adverse events and proportion of mothers with serious adverse events, proportion of infants with adverse events not considered serious, and proportion of mothers with detectable HBV DNA before delivery because the certainty of evidence was very low. Only one or two trials, with insufficient power, contributed data for analyses. We lack randomised clinical trials at low risk of systematic and random errors, and fully reporting all-cause infant mortality, serious adverse events and reporting on clinical and laboratory outcomes, such as infants with HBV mother-to-child transmission, all-cause maternal mortality, maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion before delivery and maternal adverse events not considered serious.

Randomized control trial on effectiveness and safety of direct trocar versus Veress needle entry techniques in obese women during diagnostic laparoscopy.

PURPOSE: To determine the benefits and safety of direct trocar insertion versus Veress needle technique in obese women undertaking diagnostic laparoscopy procedures. METHODS: Randomized-controlled trial on 135 obese women undergoing diagnostic laparoscopy and dye test for infertility was conducted. Women were randomly assigned to either direct trocar access (n = 68) or Veress needle access (n = 67) before achieving pneumoperitoneum. The same surgeon executed the laparoscopic techniques with a single-puncture technique. The primary outcome measures included total length of the procedure and incidence of any complications, while the mean laparoscopic entry time, volume of CO2 required, and total of tries needed to attain successful entry were secondary outcomes. Intention-to-treat principle was applied to analysis. RESULTS: Women in both groups had similar socio-demographic and clinical characteristics and none were lost to follow-up. The overall length of the procedure was significantly lesser in the direct trocar group compared to the Veress needle group (9.9 ± 6.0 vs 16.7 ± 4.7 min; p < 0.001). No significant differences occurred in other outcomes including mean entry time, volume of CO2 used, number of attempts for successful entry, and major/minor complications (p > 0.05). CONCLUSIONS: Direct trocar technique may be an effective alternative to Veress needle for pneumoperitoneum in obese women for diagnostic laparoscopy. It has a comparable rapid laparoscopic entry time but a significantly lower duration of the procedure and shorter exposure to anesthesia. Both methods are equally effective as there was no significant difference in the complications recorded. A greater sample trial may be essential for more corroborative substantiation. CLINICAL TRIAL REGISTRATION: PACTR201510000999192.

Diagnostic value of Chorioquick for detecting chorioamnionitis in women with premature rupture of membranes.

OBJECTIVE: To determine the accuracy of a semi-quantitative interleukin-6 (IL-6) vaginal secretion rapid test (Chorioquick) for detecting chorioamnionitis in women with premature rupture of membranes (PROM). METHODS: A prospective cohort study in five tertiary hospitals in Nigeria involved women with confirmed PROM at term and preterm PROM with or without suspected chorioamnionitis from August 1, 2017, to October 31, 2018. Cervicovaginal fluid samples were tested for chorioamnionitis using the Chorioquick test. Samples were repeated at decision to deliver. The test was considered positive if at least the indicator 'IL-6 low' of the three Chorioquick biomarkers (low, medium, high) was positive, or negative if none of the biomarkers were positive. Chorioamnionitis was histologically confirmed post-delivery using three tissue samples. Primary outcome measures were sensitivity, specificity, and accuracy. RESULTS: Of 73 women, on histological confirmation, 39 were true positive and 29 were true negative (for chorioamnionitis) to the Chorioquick test at repeat assessment. Overall, the Chorioquick test had a sensitivity of 97.5% (95% confidence interval [CI] 85.3-99.9), specificity 87.9% (70.9-96.0), and accuracy 93.2% (79.5-99.1). Sub-group analysis of women <37 weeks of pregnancy showed a sensitivity of 100.0% (95% CI 83.4-100.0), specificity of 91.3% (70.5-98.5), and accuracy of 95.8% (82.5-99.5). Triple positive samples were 100.0% specific in all gestations. CONCLUSION: Chorioquick showed favorable utility for detecting chorioamnionitis in PROM and could be a reliable, non-invasive rapid tool in a real-world clinical setting.

Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations.

BACKGROUND: The presence of deleterious mutations in breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2) significantly increases the risk of developing some cancers, such as breast and high-grade serous cancer (HGSC) of ovarian, tubal and peritoneal origin. Risk-reducing salpingo-oophorectomy (RRSO) is usually recommended to BRCA1 or BRCA2 carriers after completion of childbearing. Despite prior systematic reviews and meta-analyses on the role of RRSO in reducing the mortality and incidence of breast, HGSC and other cancers, RRSO is still an area of debate and it is unclear whether RRSO differs in effectiveness by type of mutation carried. OBJECTIVES: To assess the benefits and harms of RRSO in women with BRCA1 or BRCA2 mutations. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 7) in The Cochrane Library, MEDLINE Ovid, Embase Ovid and trial registries, with no language restrictions up to July 2017. We handsearched abstracts of scientific meetings and other relevant publications. SELECTION CRITERIA: We included non-randomised trials (NRS), prospective and retrospective cohort studies, and case series that used statistical adjustment for baseline case mix using multivariable analyses comparing RRSO versus no RRSO in women without a previous or coexisting breast, ovarian or fallopian tube malignancy, in women with or without hysterectomy, and in women with a risk-reducing mastectomy (RRM) before, with or after RRSO. DATA COLLECTION AND ANALYSIS: We extracted data and performed meta-analyses of hazard ratios (HR) for time-to-event variables and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (CI). To assess bias in the studies, we used the ROBINS-I 'Risk of bias' assessment tool. We quantified inconsistency between studies by estimating the I2 statistic. We used random-effects models to calculate pooled effect estimates. MAIN RESULTS: We included 10 cohort studies, comprising 8087 participants (2936 (36%) surgical participants and 5151 (64%) control participants who were BRCA1 or BRCA2 mutation carriers. All the studies compared RRSO with or without RRM versus no RRSO (surveillance). The certainty of evidence by GRADE assessment was very low due to serious risk of bias. Nine studies, including 7927 women, were included in the meta-analyses. The median follow-up period ranged from 0.5 to 27.4 years. MAIN OUTCOMES: overall survival was longer with RRSO compared with no RRSO (HR 0.32, 95% CI 0.19 to 0.54; P < 0.001; 3 studies, 2548 women; very low-certainty evidence). HGSC cancer mortality (HR 0.06, 95% CI 0.02 to 0.17; I² = 69%; P < 0.0001; 3 studies, 2534 women; very low-certainty evidence) and breast cancer mortality (HR 0.58, 95% CI 0.39 to 0.88; I² = 65%; P = 0.009; 7 studies, 7198 women; very low-certainty evidence) were lower with RRSO compared with no RRSO. None of the studies reported bone fracture incidence. There was a difference in favour of RRSO compared with no RRSO in terms of ovarian cancer risk perception quality of life (MD 15.40, 95% CI 8.76 to 22.04; P < 0.00001; 1 study; very low-certainty evidence). None of the studies reported adverse events.Subgroup analyses for main outcomes: meta-analysis showed an increase in overall survival among women who had RRSO versus women without RRSO who were BRCA1 mutation carriers (HR 0.30, 95% CI 0.17 to 0.52; P < 0001; I² = 23%; 3 studies; very low-certainty evidence) and BRCA2 mutation carriers (HR 0.44, 95% CI 0.23 to 0.85; P = 0.01; I² = 0%; 2 studies; very low-certainty evidence). The meta-analysis showed a decrease in HGSC cancer mortality among women with RRSO versus no RRSO who were BRCA1 mutation carriers (HR 0.10, 95% CI 0.02 to 0.41; I² = 54%; P = 0.001; 2 studies; very low-certainty evidence), but uncertain for BRCA2 mutation carriers due to low frequency of HGSC cancer deaths in BRCA2 mutation carriers. There was a decrease in breast cancer mortality among women with RRSO versus no RRSO who were BRCA1 mutation carriers (HR 0.45, 95% CI 0.30 to 0.67; I² = 0%; P < 0.0001; 4 studies; very low-certainty evidence), but not for BRCA2 mutation carriers (HR 0.88, 95% CI 0.42 to 1.87; I² = 63%; P = 0.75; 3 studies; very low-certainty evidence). One study showed a difference in favour of RRSO versus no RRSO in improving quality of life for ovarian cancer risk perception in women who were BRCA1 mutation carriers (MD 10.70, 95% CI 2.45 to 18.95; P = 0.01; 98 women; very low-certainty evidence) and BRCA2 mutation carriers (MD 13.00, 95% CI 3.59 to 22.41; P = 0.007; very low-certainty evidence). Data from one study showed a difference in favour of RRSO and RRM versus no RRSO in increasing overall survival (HR 0.14, 95% CI 0.02 to 0.98; P = 0.0001; I² = 0%; low-certainty evidence), but no difference for breast cancer mortality (HR 0.78, 95% CI 0.51 to 1.19; P = 0.25; very low-certainty evidence). The risk estimates for breast cancer mortality according to age at RRSO (50 years of age or less versus more than 50 years) was not protective and did not differ for BRCA1 (HR 0.85, 95% CI 0.64 to 1.11; I² = 16%; P = 0.23; very low-certainty evidence) and BRCA2 carriers (HR 0.88, 95% CI 0.42 to 1.87; I² = 63%; P = 0.75; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very low-certainty evidence that RRSO may increase overall survival and lower HGSC and breast cancer mortality for BRCA1 and BRCA2 carriers. Very low-certainty evidence suggests that RRSO reduces the risk of death from HGSC and breast cancer in women with BRCA1 mutations. Evidence for the effect of RRSO on HGSC and breast cancer in BRCA2 carriers was very uncertain due to low numbers. These results should be interpreted with caution due to questionable study designs, risk of bias profiles, and very low-certainty evidence. We cannot draw any conclusions regarding bone fracture incidence, quality of life, or severe adverse events for RRSO, or for effects of RRSO based on type and age at risk-reducing surgery. Further research on these outcomes is warranted to explore differential effects for BRCA1 or BRCA2 mutations.

Spontaneous Synchronous Tubal Pregnancy with Prior Successful in Vitro Fertilization and Embryo Transfer. A Case Report.

BACKGROUND: Synchronous (bilateral) ectopic preg- nancy is a very rare gynecological entity resulting in most cases from assisted reproduction techniques. Al- though few cases of bilater- al ectopic pregnancy have been reported in Nigeria, spontaneous bilateral tubal pregnancy in a woman with a diagnosis of bilateral tubal blockage and prior success- ful in vitro fertilization and embryo transfer (IVF-E T) is paradoxically rare and, to the best of our knowledge, has not been reported in Nigeria. CASE: A 37-year-old Nigerian woman presented with ruptured ectopic pregnancy associated with hemoperito- neum with previous diagnosis of bilateral tubal blockage and prior successful IVF-ET She subsequently under- went a laparotomy and the diagnosis of bilateral tubal pregnancy was made during surgery and confirmed by histology. Bilateral salpingectomy was done. CONCLUSION: This was the first case of spontaneous bilateral tubal pregnancy in a woman with previous di- agnosis of bilateral tubal blockage and prior successful IVF-ET in Nigeria. There is no evidence-based guideline presently available on the management of bilateral ectopic pregnancy.