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Byline: Vikash. Goel, Neelam. Dogra, Mamta. Khandelwal, R. Chaudhri Sir, Proper positioning is a prerequisite for successful endotracheal intubation. A giant occipital encephalocele may prevent this. We report such a [...]

Efforts to improve bone resrponse to biomaterials have focused on ligands that bind a5131 integrins. However, antibodies to α5β1 reduce osteoblast proliferation but do not affect differentiation when cells are grown on titanium (Ti). β1-silencing blocks the differentiation stimulus of Ti microtopography, suggesting that other β1 partners are important. Stably α2-silenced MG63 human osteoblast-like cells were used to test whether α2β1 specifically mediates osteoblast response to Ti surface micron-scale structure and energy. WI and α2-silenced MG63 cells were cultured on tissue culture polystyrene (TCPS) and Ti disks with different surface microtopographies: machined pretreatment (PT) surfaces [mean peak to valley roughness (R[suba]) < 0.02 μm], PT surfaces that were grit-blasted and acid-etched (S LA; R[suba] = 4 μm), and SLA with high surface energy (modSLA). Alkaline phosphatase (ALP), α2 and β1 mRNA, but not α5, αv, β3, type-I collagen, or osteocalcin, increased on SLA and modSLA at 6 days. α2 increased at 8 days on TCPS and PT, but remained unchanged on SLA and modSLA. α2-protein was reduced 70% in α2-siRNA cells, whereas α5-mRNA and protein were unaffected. α2-knockdown blocked surface-dependent increases in β1 and osteocalcin and decreases in cell number and increases in ALP and local factors typical of MG63 cells grown on SLA and modSLA [e.g., prostaglandin E[sub2], osteoprotegerin, latent and active TGF-β1, and stimulatory effects of lα,25(OH)[sub2]D[sub3] on these parameters]. This finding indicates that α2β1 signaling is required for osteoblastic differentiation caused by Ti microstructure and surface energy, suggesting that conclusions based on cell behavior on TCPS are not predictive of behavior on other substrates or the mechanisms involved. [ABSTRACT FROM AUTHOR]

Abstract Background Osseointegration depends on the implant surface, bone quality and the local and systemic host environment, which can differ in male and female patients. This study was undertaken in order to determine if male and female cells respond differently to titanium surfaces that have micron-scale roughness and if interactions of calciotropic hormones [1α,25(OH)2D3 and 17β-oestradiol (E2)] and microstructured surfaces on osteoblasts are sex dependent. Methods Osteoblasts from 6-week old Sprague-Dawley rats were cultured on tissue culture polystyrene (TCPS) or on titanium (Ti) disks with two different surface topographies, a smooth pretreated (PT) surface and a coarse grit-blasted/acid-etched (SLA) surface, and treated with 1α,25(OH)2D3, E2, or E2 conjugated to bovine serum albumin (E2-BSA). Results Male and female cells responded similarly to Ti microstructure with respect to cell number and levels of osteocalcin, transforming growth factor-β1, osteoprotegerin and prostaglandin E2 in their conditioned media, exhibiting a more differentiated phenotype on SLA than on PT or TCPS. E2 and E2-BSA increased differentiation and local factor production, an effect that was microstructure dependent and found only in female osteoblasts. 1α,25(OH)2D3 increased osteoblast differentiation and local factor production in female and male cells, but the effect was more robust in male cells. Conclusions Male and female rat osteoblasts respond similarly to surface microstructure but exhibit sexual dimorphism in substrate-dependent responses to systemic hormones. Oestrogen affected only female cells while 1α,25(OH)2D3 had a greater effect on male cells. These results suggest that successful osseointegration in males and females may depend on the implant surface design and correct levels of calciotropic hormones.

Background: Each year world-wide about 65 million people sustain a mild traumatic brain injury (mTBI). Fatigue is a common and distressing symptom after mTBI. We examine the effect of tranexamic acid (TXA) on fatigue in patients with mTBI using data from the CRASH-3 trial., Methods: The CRASH-3 trial randomised 9,202 patients with traumatic brain injury and no significant extracranial bleeding to receive TXA or placebo within 3 hours of injury. The primary outcome was death from head injury within 28 days of injury. The methods and results are presented elsewhere. Fatigue was recorded as "None", "Moderate" or "Extreme." This study examines the effect of TXA on extreme fatigue in the 2,632 patients with mTBI (Glasgow Coma Scale [GCS] score≥13). Our analyses were not prespecified., Results: Our study primary outcome, extreme fatigue, was reported for 10 (0.8%) of 1,328 patients receiving TXA and 19 (1.5%) of 1,288 patients receiving placebo (risk ratio [RR]=0.51, 95% confidence interval [CI] 0.24-1.09). Death within 28 days of injury was reported for 34 (2.6%) of 1,328 patients receiving TXA versus 47 (3.6%) of 1,288 patients receiving placebo (RR=0.70, 95% CI 0.45-1.08). Among patients allocated to TXA, 44 (3.3%) patients either died or reported extreme fatigue versus 66 (5.1%) patients among those allocated to placebo (RR=0.65, 95% CI 0.44-0.94). This composite outcome is disproportionately influenced by deaths which account for 74% (81 from 110) of events., Conclusions: We found no evidence that tranexamic acid reduces fatigue in patients with mTBI. Given, 1) our analyses were not prespecified, 2) our outcome measure is not based on a validated fatigue severity scale, and 3) TBI patients can suffer from hospital-induced delirium, which hinders clinician assessment, these results need to be replicated in another study., Registration: ISRCTN (ISRCTN15088122, 19/07/2011), ClinicalTrials.gov (NCT01402882, 26/07/2011), EudraCT (2011-003669-14, 25/07/2011), Pan African Clinical Trial Registry (PACTR20121000441277, 30/10/2012)., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Mansukhani R et al.)

Background: Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth., Methods: In this systematic review and IPD meta-analysis, we searched the WHO International Clinical Trials Registry Platform from database inception to Aug 4, 2024 for randomised trials that assessed the effects of tranexamic acid in women giving birth. Trials were eligible if they were prospectively registered, placebo-controlled, included more than 500 women, and had a low risk of bias for random sequence generation and allocation concealment. IPD were requested from the trial investigators. The primary outcomes were the numbers of women with life-threatening bleeding and thromboembolic events. We used a one-stage model to analyse the data and explored whether the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia, or timing of administration (before or after a diagnosis of postpartum haemorrhage). This study is registered with PROSPERO, CRD42022345775., Findings: We analysed data on 54 404 women from five trials. We obtained IPD for 43 409 women from four trials and aggregate data on 10 995 women from one trial. All trials had a low risk of bias. Life-threatening bleeding occurred in 178 (0·65%) of 27 300 women in the tranexamic acid group versus 230 (0·85%) of 27 093 women in the placebo group (pooled odds ratio [OR] 0·77 [95% CI 0·63-0·93]; p=0·008). There was no evidence that the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia or timing of administration. No significant difference was identified between tranexamic acid and placebo groups with regard to thromboembolic events: 50 (0·2%) of 26 571 women in the tranexamic acid group had fatal or non-fatal thromboembolic events versus 52 (0·2%) of 26 373 women in the placebo group (pooled OR 0·96 [0·65-1·41]; p=0·82) with no significant heterogeneity identified in the subgroup analyses., Interpretation: Tranexamic acid reduces the risk of life-threatening postpartum bleeding. We found no evidence that tranexamic acid increases the risk of thrombosis. Although we do not recommend the use of tranexamic acid in all women giving birth, consideration should be given to its use before a diagnosis of postpartum haemorrhage in women at high risk of death., Funding: The Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests IR and HS-S declare receipt of support from the National Institute for Health and Care Research, Wellcome, and the John Moulton Foundation for support of their other research activities into the effects of tranexamic acid. All payments were made to their employing institution (London School of Hygiene & Tropical Medicine). IR also declares an unpaid role as convenor of an ad-hoc group (The Joint Royal Colleges tranexamic acid in surgery implementation group) to increase the use of tranexamic acid in surgical patients as per National Institute for Health and Care Excellence guidance. LS reports receipt of payment or honoraria from Ferring Pharmaceuticals, Norgine, Bayer, Pfizer, GlaxoSmithKline, and Organon for lectures, presentations, speakers bureaus, manuscript writing, or educational events. HA declares receipt of support from the National Institute of Child Health and Human Development/National Institutes of Health for grant OPTIMUM OB-TXA: Optimal TIMing, route and dose of tranexamic acid prior to UMbilical cord clamp for postpartum haemorrhage prevention; consulting fees from Hemosonics, Coagulant Therapeutics, Hemosquid; and payment or honoraria from COR2ED for lectures, presentations, speakers bureaus, manuscript writing, or educational events. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Postpartum haemorrhage (PPH) causes about 70,000 maternal deaths every year. Tranexamic acid (TXA) is a life-saving treatment for women with PPH. Intravenous (IV) TXA reduces deaths due to PPH by one-third when given within 3 h of childbirth. Because TXA is more effective when given early and PPH usually occurs soon after childbirth, giving TXA just before childbirth might prevent PPH. Although several randomised trials have examined TXA for PPH prevention, the results are inconclusive. Because PPH only affects a small proportion of births, we need good evidence on the balance of benefits and harms before using TXA to prevent PPH. TXA is usually given by slow IV injection. However, recent research shows that TXA is well tolerated and rapidly absorbed after intramuscular (IM) injection, achieving therapeutic blood levels within minutes of injection., Methods: The I'M WOMAN trial is an international, multicentre, three-arm, randomised, double-blind, placebo-controlled trial to assess the effects of IM and IV TXA for the prevention of PPH in women with one or more risk factors for PPH giving birth vaginally or by caesarean section., Discussion: The trial will provide evidence of the benefits and harms of TXA for PPH prevention and the effects of the IM and IV routes of administration. The IM route should be as effective as the IV route for preventing bleeding. There may be fewer side effects with IM TXA because peak blood concentrations are lower than with the IV route. IM TXA also has practical advantages as it is quicker and simpler to administer. By avoiding the need for IV line insertion and a slow IV injection, IM administration would free up overstretched midwives and doctors to focus on looking after the mother and baby and expand access to timely TXA treatment., Trial Registration: ClinicalTrials.gov NCT05562609. Registered on 3 October 2022. ISRCTN Registry ISRCTN12590098. Registered on 20 January 2023. Pan African Clinical Trial Registry PACTR202305473136570. Registered on 18 May 2023., (© 2023. The Author(s).)

Objective: To examine the safety, efficacy and pharmacology of intravenous (IV), intramuscular (IM) and oral tranexamic acid (TXA) use in pregnant women., Design: Randomised, open-label trial., Setting: Hospitals in Pakistan and Zambia., Population: Women giving birth by caesarean section., Methods: Women were randomised to receive 1 g IV, 1 g IM, 4 g oral TXA or no TXA. Adverse events in women and neonates were recorded. TXA concentration in whole blood was measured and the concentrations over time were examined with population pharmacokinetics. The relationship between drug exposure and D-dimer was explored. The trial registration is NCT04274335., Main Outcome Measures: Concentration of TXA in maternal blood., Results: Of the 120 women included in the randomised safety study, there were no serious maternal or neonatal adverse events. TXA concentrations in 755 maternal blood and 87 cord blood samples were described by a two-compartment model with one effect compartment linked by rate transfer constants. Maximum maternal concentrations were 46.9, 21.6 and 18.1 mg/L for IV, IM and oral administration, respectively, and 9.5, 7.9 and 9.1 mg/L in the neonates. The TXA response was modelled as an inhibitory effect on the D-dimer production rate. The half-maximal inhibitory concentration (IC 50 ) was 7.5 mg/L and was achieved after 2.6, 6.4 and 47 minutes with IV, IM and oral administration of TXA, respectively., Conclusions: Both IM and oral TXA are well tolerated. Oral TXA took about 1 hour to reach minimum therapeutic concentrations and would not be suitable for emergency treatment. Intramuscular TXA inhibits fibrinolysis within 10 minutes and may be a suitable alternative to IV., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Postpartum haemorrhage (PPH) is responsible for over 50,000 maternal deaths every year. Most of these deaths are in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases surgical bleeding and reduces deaths from bleeding after traumatic injury. When given within three hours of birth, TXA reduces deaths from bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. World-wide, over one-third of pregnant women are anaemic and many are severely anaemic. These women have an increased risk of PPH and are more likely to die if PPH occurs. There is an urgent need to identify ways to prevent severe postpartum bleeding in anaemic women. The WOMAN-2 trial will quantify the effects of TXA on postpartum bleeding in women with anaemia. Results: This statistical analysis plan (version 1.0; dated 22 February 2023) has been written based on information in the WOMAN-2 Trial protocol version 2.0, dated 30 June 2022. The primary outcome of the WOMAN-2 trial is the proportion of women with a clinical diagnosis of primary PPH. Secondary outcomes are maternal blood loss and its consequences (estimated blood loss, haemoglobin, haemodynamic instability, blood transfusion, signs of shock, use of interventions to control bleeding); maternal health and wellbeing (fatigue, headache, dizziness, palpitations, breathlessness, exercise tolerance, ability to care for her baby, health related quality of life, breastfeeding); and other health outcomes (deaths, vascular occlusive events, organ dysfunction, sepsis, side effects, time spent in higher level facility, length of hospital stay, and status of the baby). Conclusions: WOMAN-2 will provide reliable evidence about the effects of TXA in women with anaemia. Registration: WOMAN-2 was prospectively registered at the International Standard Randomised Controlled Trials registry ( ISRCTN62396133) on 07/12/2017 and ClinicalTrials.gov on 23/03/2018 ( NCT03475342)., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Collier T et al.)

Background: Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics.   Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775).  Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat.   PROSPERO registration: CRD42022345775  Keywords   Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis., Competing Interests: Competing interests: LS reports receiving lecture and consulting fees from Ferring. No competing interests were disclosed for any other author., (Copyright: © 2023 The Anti-fibrinolytics Trialists Collaborators – Obstetric Trialists Group et al.)

Background: Person-Centered Maternity Care (PCMC) is known as one of the most important components of maternal care. Every woman has the ultimate right of respectful health care. Previous research documents that lack of supportive care and respectful behavior experienced by pregnant women can act as a barrier to the utilization of health care services. Few studies have used PCMC tool to document this phenomenon. The objective of this descriptive study was to assess the women's perception of PCMC in Pakistan., Methods: Three hundred and seventy-seven (377) postnatal women of ages 18-49 years participated in the research. The study sites were secondary and tertiary care hospitals located in the twin cities of Rawalpindi and Islamabad. The PCMC tool used in this study is a validated scale with three sub-domains of i) communication and autonomy, ii) supportive care, and iii) dignity and respect. Data was analyzed using SPSS version 16, and descriptive and bivariate analysis was undertaken., Results: The PCMC mean score was 54 ± [10.7] out of 90. About half (55%) of women had good perception of PCMC. Sub-domain of supportive care scored the lowest as compared to the other two domains. Overall, 36% women reported physical abuse while 22% reported verbal abuse at the hands of the healthcare providers. Most of the women (88%) said that health providers did not introduce themselves. About 30% women claimed that health care providers never asked for permission before doing any medical procedures and 20% of women claimed that doctors did not describe the purpose of examination while 178 (47%) of women said that health provider explained the purpose of medications all the time, additionally, about 14% were never given the choice to ask questions., Conclusion: The study concluded that the majority of postnatal women perceived that they were not getting optimum Person-Centered Maternity Care. Some core aspects in supportive care domain were missing. In order to improve the quality of hospital-based childbirths, efforts are needed to improve the quality of care., (© 2023. The Author(s).)

Background: Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias., Objective: The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding., Design: A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat., Setting: The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine., Participants: Adults with significant upper or lower gastrointestinal bleeding ( n  = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery., Intervention: Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo., Main Outcome Measures: The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit., Results: A total of 12,009 patients were allocated to receive tranexamic acid ( n  = 5994, 49.9%) or the matching placebo ( n  = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid., Conclusions: Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding., Future Work: These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes., Limitations: Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid., Trial Registration: Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.

Objectives: To understand the acceptability and feasibility of sexually transmitted infection (STI) testing during antenatal care, along with the prevalence of STIs, in Rawalpindi, Pakistan. Methods: We enrolled pregnant women seeking antenatal care and performed STI testing using Cepheid GeneXpert® CT/NG and TV kits and Alere Determine™ HIV and syphilis tests. We used interviewer-administered surveys to collect medical, social, and sexual histories. Participants testing positive for STIs and their partners were treated. Results: We enrolled 1001 women from September to December 2019. Nearly all women offered to participate in this study enrolled. Most women understood the effects an STI can have on their pregnancy (99.6%) and valued STI screening during pregnancy (98.1%). 11 women tested positive for any STI: ( Chlamydia trachomatis = 4, Neisseria gonorrhoeae = 1, and Trichomonas vaginalis = 6). Of those, six presented for a test-of-cure, and two were positive for Trichomonas vaginalis . None tested positive for HIV infection or syphilis ( n = 503). Conclusions: STI testing during antenatal care in Rawalpindi was acceptable, valued, understood, and feasible. The prevalence of STIs in pregnant women was low. Continued prevalence monitoring is warranted.

Background: Intravenous tranexamic acid (TXA) within 3 hours of birth significantly reduces death due to bleeding in women with postpartum haemorrhage (PPH). Most PPH deaths occur in the first hours after giving birth and treatment delay decreases survival.  One barrier to rapid TXA treatment is the need for intravenous injection. Intramuscular injection and oral solution of TXA would be easier and faster to administer and would require less training. However, the pharmacokinetics (PK), pharmacodynamics and safety of TXA administered by different routes in pregnant women have not been established. The main aim of this study is to ascertain whether IM and oral solution of TXA will be absorbed at levels sufficient to inhibit fibrinolysis in pregnant women. Methods: WOMAN-PharmacoTXA is a prospective, randomised, open label trial to be conducted in Zambia and Pakistan.  Adult women undergoing caesarean section with at least one risk factor for PPH will be included.  Women will be randomised to receive one of the following about 1 hour prior to caesarean section: 1-gram TXA IV, 1-gram TXA IM, 4-grams TXA oral solution or no TXA. Randomisation will continue until 120 participants with at least six post randomisation PK samples are included. TXA concentration in maternal blood samples will be measured at baseline and at different time points during 24 hours after receipt of intervention. Blood TXA concentration will be measured from the umbilical cord and neonate. The primary endpoint is maternal blood TXA concentrations over time. Secondary outcomes include umbilical cord and neonate TXA concentration D-dimer concentration, blood loss and clinical diagnosis of PPH, injection site reactions and maternal and neonate adverse events. Discussion: The WOMAN-PharmacoTXA trial will provide important data on pharmacokinetics, pharmacodynamics and safety of TXA after IV, intramuscular and oral administration in women giving birth by caesarean section. Trial registration: ClincalTrials.gov, NCT04274335 (18/02/2020)., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Arribas M et al.)

Background: Pakistan is among a number of countries facing protracted challenges in addressing maternal mortality with a concomitant weak healthcare system complexed with inequities. Sexual and reproductive health and rights (SRHR) self-care interventions offer the best solution for improving access to quality healthcare services with efficiency and economy. This manuscript documents country experience in introducing and scaling up two selected SRHR self-care interventions. A prospective qualitative study design was used and a semi-structured questionnaire was shared with identified SRHR private sector partners selected through convenience and purposive sampling. The two interventions include the use of misoprostol for postpartum hemorrhage and the use of subcutaneous depomedroxyprogesterone acetate (DMPA) as injectable contraceptive method. Data collection was done through emails and telephone follow-up calls., Results: Nine of the 13 partners consulted for the study responded. The two selected self-care interventions are mainly supported by private sector partners (national and international nongovernmental organizations) having national or subnational existence. Their mandates include all relevant areas, such as policy advocacy, field implementation, trainings, supervision and monitoring. A majority of partners reported experience related to the use of misoprostol; it was introduced more than a decade ago, is registered and is procured by both public and private sectors. Subcutaneous DMPA is a new intervention, having been introduced only recently, and commodity availability remains a challenge. It is being delivered through health workers/providers and is not promoted as a self-administered contraceptive. Community engagement and awareness raising is reported as an essential element of successful field implementation; however, no beneficiary data was collected for the study. Training approaches differ considerably, are standalone or integrated with SRHR topics and their duration varies between 1 and 5 days, covering a range of cadres., Conclusion: Pubic sector ownership and patronage is essential for introducing and scaling up self-care interventions as a measure to support the healthcare system in delivering quality sexual and reproductive health services. Supervision, monitoring and reporting are areas requiring further support, as well as the leadership and governance role of the public sector. Standardization of trainings, community awareness, supervision, monitoring and reporting are required together with integration of self-care in routine capacity building activities (pre- and in-service) on sexual and reproductive health in the country.

Background: Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients., Objective: To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness., Design: Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model., Setting: 175 hospitals in 29 countries., Participants: Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible., Intervention: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo., Main Outcome Measures: Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events., Results: Among patients treated within 3 hours of injury ( n  = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction ( p -value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury ( p  = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury ( p  = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained)., Conclusion: Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive., Future Work: Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed., Limitations: Time to treatment may have been underestimated., Trial Registration: Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277., Funding: The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.

Introduction: An estimated 69 million traumatic brain injuries (TBI) occur each year worldwide, with most in low-income and middle-income countries. The CRASH-3 randomised trial found that intravenous administration of tranexamic acid within 3 hours of injury reduces head injury deaths in patients sustaining a mild or moderate TBI. We examined the cost-effectiveness of tranexamic acid treatment for TBI., Methods: A Markov decision model was developed to assess the cost-effectiveness of treatment with and without tranexamic acid, in addition to current practice. We modelled the decision in the UK and Pakistan from a health service perspective, over a lifetime time horizon. We used data from the CRASH-3 trial for the risk of death during the trial period (28 days) and patient quality of life, and data from the literature to estimate costs and long-term outcomes post-TBI. We present outcomes as quality-adjusted life years (QALYs) and 2018 costs in pounds for the UK, and US dollars for Pakistan. Incremental cost-effectiveness ratios (ICER) per QALY gained were estimated, and compared with country specific cost-effective thresholds. Deterministic and probabilistic sensitivity analyses were also performed., Results: Tranexamic acid was highly cost-effective for patients with mild TBI and intracranial bleeding or patients with moderate TBI, at £4288 per QALY in the UK, and US$24 per QALY in Pakistan. Tranexamic acid was 99% and 98% cost-effective at the cost-effectiveness thresholds for the UK and Pakistan, respectively, and remained cost-effective across all deterministic sensitivity analyses. Tranexamic acid was even more cost-effective with earlier treatment administration. The cost-effectiveness for those with severe TBI was uncertain., Conclusion: Early administration of tranexamic acid is highly cost-effective for patients with mild or moderate TBI in the UK and Pakistan, relative to the cost-effectiveness thresholds used. The estimated ICERs suggest treatment is likely to be cost-effective across all income settings globally., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)