Coomarasamy A, Devall AJ, Bell S
… +19 more, Sindhu KN, Mammoliti KM, Nausheen S, Ali-Masri H, Deneux-Tharaux C, Homer CSE, Miller S, Kihara A, Thangaratinam S, Weeks A, Wright A, Hodgetts-Morton V, Beeson LE, Allotey J, Sobhy S, Moran N, Yunas I, Oladapo OT, Gallos ID
Postpartum haemorrhage (PPH) is common, affecting an estimated 13% of women having vaginal birth and 31% of women having caesarean birth. Successful management of PPH requires early and accurate diagnosis and effective t...Postpartum haemorrhage (PPH) is common, affecting an estimated 13% of women having vaginal birth and 31% of women having caesarean birth. Successful management of PPH requires early and accurate diagnosis and effective treatment. A systematic review found that subjective visual estimation of blood loss misses 52% of PPH diagnoses at vaginal birth (pooled sensitivity 48%, 95% CI 44-53), and probably more at caesarean birth. The WHO-International Federation of Gynecology and Obstetrics-International Confederation of Midwives consolidated guidelines on PPH therefore recommend objective quantification of blood loss with products such as a calibrated blood collection drape. When supported by a robust implementation strategy and a first-response treatment bundle, objective measurement of blood loss and monitoring of vital signs has been shown to diagnose PPH accurately and early, and improve clinical outcomes. Refractory PPH can progress to life-threatening PPH, which should be managed by a multidisciplinary team providing aggressive resuscitation and targeted treatment. Saving the life of a woman with excessive postpartum bleeding is a race against time. The six delays to avoid are: (1) in the diagnosis (by use of objective cumulative blood loss measurement and early trigger criteria), (2) in the first-response treatment (by authorising midwives to administer all components of a standardised bundle of interventions), (3) in the escalation (by use of explicit escalation criteria and red flags), (4) in the use of temporising measures (eg, non-pneumatic anti-shock garment), (5) in the identification and targeted management of any specific causes of bleeding, and (6) in the provision of blood and blood products. Quick actions to avoid these delays can mean the difference between life and death for a woman with PPH.
Coomarasamy A, Sindhu KN, Gallos I
… +16 more, Periyathambi N, Price MJ, Yunas I, Qureshi Z, Muriithi FG, Williams CR, Fawcus S, George A, Althabe F, Titulaer P, Aswat A, Cresswell JA, Arulkumaran S, Scott N, Devall AJ, Oladapo OT
Excessive bleeding after childbirth, known as postpartum haemorrhage (PPH), can turn an uncomplicated birth into a catastrophe. Each year, PPH occurs in an estimated 27 million women worldwide-17 million after vaginal bi...Excessive bleeding after childbirth, known as postpartum haemorrhage (PPH), can turn an uncomplicated birth into a catastrophe. Each year, PPH occurs in an estimated 27 million women worldwide-17 million after vaginal birth and 10 million during or after caesarean birth. An estimated 43 000 women die from PPH annually, translating to a death every 12 min. The pooled prevalence of PPH at vaginal birth is 12·6% (95% CI 10·1-15·2) and at caesarean birth 30·9% (95% credible interval 24·9-37·6), based on the conventional definition of PPH. Common causes of PPH are uterine atony, genital tract trauma, retained placenta, abnormal placentation, and coagulopathy. Risk factors include caesarean birth, multiple pregnancy, anaemia, high maternal BMI, previous PPH, female genital mutilation, sepsis, pre-eclampsia, macrosomia, and inadequate antenatal care. In addition to being the leading cause of maternal mortality worldwide, the consequences of PPH include serious morbidities such as severe anaemia, hysterectomy, organ failure, and long-term psychological trauma. The global economic burden of PPH is estimated at US$10·4 billion (95% credible interval $9·8-13·2 billion) annually, consisting of $3·6 billion ($3·2-6·2 billion) for health systems and $6·8 billion ($6·2-7·5 billion) for societies. Based on a rigorous review of the evidence, WHO has recently redefined PPH as objectively measured blood loss of at least 300 mL plus an abnormal haemodynamic sign, or objectively measured blood loss of at least 500 mL, whichever occurs first. This new definition prioritises early PPH diagnosis and treatment to avert life-threatening maternal outcomes. Comprehensive efforts to address missed opportunities in the prevention, diagnosis, and treatment of PPH are needed to improve outcomes. These efforts include addressing the unmet need for contraception, mitigating modifiable risks such as anaemia, avoiding caesarean sections that are not medically indicated, using effective single uterotonic prophylaxis for all births and combination prophylaxis for women at high risk of PPH, ensuring accurate and objective measurement of blood loss for early PPH diagnosis, and promptly implementing treatment with an evidence-based bundle. The PPH Roadmap (2023-30) provides a global framework for action.
Postpartum haemorrhage (PPH) is a leading cause of maternal death. Preventing PPH can spare women from experiencing the trauma and risks of PPH, reduce the strain on overstretched health systems, and probably produce bet...Postpartum haemorrhage (PPH) is a leading cause of maternal death. Preventing PPH can spare women from experiencing the trauma and risks of PPH, reduce the strain on overstretched health systems, and probably produce better outcomes than a strategy solely focused on PPH treatment. Prevention of PPH is often interpreted as provision of uterotonic drugs to contract the uterus at the time of childbirth. Although uterotonics are a central strategy for PPH prevention, several other approaches can prevent PPH or ameliorate its severity. These approaches include addressing the unmet need for contraception, remedying anaemia and other modifiable risk factors for PPH, optimising medical conditions that predispose to PPH, and tackling the rise in caesarean births in many countries. Effective delivery of preventive care requires early and regular antenatal care and planned birth at appropriately resourced health facilities. Social and behavioural change interventions for improving contraceptive provision and uptake, targeting adolescents, postpartum women, geographically remote communities, and families on low income, are a priority. Effective interventions to tackle anaemia include the management of heavy menstrual bleeding, pre-pregnancy or antenatal haemoglobin testing and oral or intravenous iron treatment, dietary improvements, and-on rare occasions-blood transfusion. Risk factors for PPH that need attention include high BMI, multiple pregnancy, gestational diabetes, pre-eclampsia, macrosomia, and several medical conditions. Caesarean births are associated with a substantial increase in PPH risk and should therefore only be done when medically indicated. A Cochrane network meta-analysis of 122 trials, with 121 931 women, found that the combinations of oxytocin plus misoprostol, or oxytocin plus ergometrine, were the most effective prophylaxis for PPH when given at the time of childbirth; however, these combinations had a higher risk of side-effects compared with single-drug prophylaxis. Oxytocin and carbetocin were the most effective single drugs for PPH prophylaxis, with minimal side-effects. Single uterotonic prophylaxis with either oxytocin or carbetocin is, therefore, recommended for routine prophylaxis. However, if oxytocin or carbetocin is not accessible, misoprostol is an alternative. Combination prophylaxis with oxytocin plus misoprostol can be considered for women at high risk of PPH. Ergometrine alone and oxytocin plus ergometrine combination are no longer recommended due to hypertension-related safety concerns. A robust implementation approach that engages various stakeholders to promote change, ensures the supply of quality-assured medicines and devices, provides training and support, and secures ongoing political and financial commitment is necessary to translate evidence into global impact.
BACKGROUND: The 2016 Chilean Food Labelling and Advertising Law (FLAL), featuring black octagonal front-of-package warning labels and marketing and school restrictions, was among the first sets of multiple healthy food p...BACKGROUND: The 2016 Chilean Food Labelling and Advertising Law (FLAL), featuring black octagonal front-of-package warning labels and marketing and school restrictions, was among the first sets of multiple healthy food policies globally. In spite of its relevance, no study has causally linked the FLAL implementation to health outcomes. We aimed to estimate the plausible causal effect of the implementation of phase 1 of the FLAL on the relevance of excess weight among young children. METHODS: In this cohort difference-in-differences approach, we assessed the effect of phase 1 of the FLAL on children's BMI when initital thresholds for critical nutrients were subsequently increased and implemented. Our analysis used national administrative data from the Chilean National Board of School Aid and Scholarships covering more than 300 000 school children aged 4-6 years across public and publicly subsidised schools nationwide from 2012 to 2017. We primarily used the Nutritional Map (Mapa Nutricional), available beginning in 2012, complemented with the Vulnerability Survey (Encuesta de Vulnerabilidad), available beginning in 2019. We defined cohorts by the year students entered prekindergarten, and compared unexposed cohorts (2012 and 2013, control group) with cohorts exposed to phase 1 (2014 and 2015, treatment group) during prekindergarten, kindergarten, and first grade. The primary outcome was a binary indicator of excess weight (ie, overweight or obesity) analysed using logit models and reported as marginal effects. We conducted subgroup analyses by children's school type, school area, maternal education and age at childbirth, birthweight, and gender. FINDINGS: The final analytical sample included 321 597 students (of cohorts 2012-15) covering the years 2012 to 2017 across prekindergarten, kindergarten, and first grade. Exposure to phase 1 of the FLAL led to significant reductions in the probability of a child having excess weight. Children exposed during both kindergarten and first grade (ie, 18 months of exposure) had the largest effects. Girls had a 2·85% lower probability of excess weight (95% CI -0·0407 to -0·0163), while boys had a 2·40% lower probability (-0·0358 to -0·0122). We also observed significant effects after 6 months of exposure (ie, first grade only): 1·91% lower probability (-0·0315 to -0·0068) for girls and 2·24% (-0·0345 to -0·0104) lower probability for boys. INTERPRETATION: Phase 1 of Chile's comprehensive FLAL plausibly caused a measurable decrease in the prevalence of excess weight among young school children. The results provide crucial, evidence-based support for policy makers worldwide who are considering food environment policies as a scalable, impactful strategy to combat the childhood obesity epidemic. FUNDING: Bloomberg Philanthropies Grant.
The global health workforce is approaching a breaking point, driven by administrative overload, inefficient workflows, burnout, and accelerating retirements, with a projected global shortfall of 11 million health profess...The global health workforce is approaching a breaking point, driven by administrative overload, inefficient workflows, burnout, and accelerating retirements, with a projected global shortfall of 11 million health professionals by 2030. This urgency coincides with the rapid emergence of clinical artificial intelligence (AI) tools, especially generative systems now embedded in documentation, triage, and workflow support. Therefore, AI should be framed less as a substitute for clinicians than as a retention strategy that preserves careers, expertise, and the human core of care. High-impact uses include ambient documentation, coding support, scheduling and demand prediction, claims and billing support, and inbox triage-tools that can reduce clerical burden and return time to caring, teaching, and leadership. Workforce shortages also create an ethical and geopolitical dilemma; reliance on international recruitment can deepen global inequities, whereas responsible AI deployment might ease competition for scarce talent and expand capacity in lower-resource settings. Yet, AI will not fix dysfunctional systems by default; poorly designed implementation can shift burdens, erode confidence, and widen gaps in health-care quality, access, and clinician wellbeing. Practice must remain clinician-led, patient-centred, and grounded in shared decision making. The policy priority is expertise amplification, not workforce replacement.
BACKGROUND: Elecoglipron is an oral, small molecule glucagon-like peptide (GLP)-1 receptor agonist currently in development for the management of type 2 diabetes. Elecoglipron is orally administered once daily with no fo...BACKGROUND: Elecoglipron is an oral, small molecule glucagon-like peptide (GLP)-1 receptor agonist currently in development for the management of type 2 diabetes. Elecoglipron is orally administered once daily with no food or fluid restrictions. SOLSTICE, a phase 2b study, evaluated the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with type 2 diabetes. METHODS: This phase 2b, randomised, double-blind, placebo-controlled trial was conducted in medical research centres and hospitals across nine countries, Canada, Germany, Hungary, Japan, Poland, Slovakia, Spain, the UK, and the USA. Sites were selected based on their capacity to fulfil protocol requirement, including, but not limited to, regulatory and ethics approvals, appropriate infrastructure and personnel, and access to the target patient population. Participants aged 18 years and older with a BMI of 23 kg/m or higher and type 2 diabetes (glycated haemoglobin [HbA] ≥7·0% to ≤10·5%, ≥6·5% to ≤10·5% in the USA) managed with diet and exercise alone or monotherapy with metformin or an SGLT2 inhibitor were enrolled. Participants were randomly assigned (3:5:3:5:3:3:6:4) via an interactive web response system to elecoglipron as oral once-daily tablets without dose escalation (5, 15, or 25 mg) or three different dose-escalation regimens, to target doses of 50 mg and 75 mg. The daily dose of 50 mg was evaluated using an every 2-week dose-escalation schedule, while 75 mg was assessed with every 2-week or every 4-week dose-escalation schedules. Participants could also be randomly assigned to placebo matched to each of the elecoglipron groups, or open-label oral semaglutide titrated to 14 mg once daily for 26 weeks. Participants, the treating physician, and the sponsor were masked to doses of elecoglipron or matched placebo, while semaglutide was open-label. The primary endpoint was percent change in HbA from baseline to 26 weeks. Efficacy, safety, and tolerability were assessed in all participants who received at least one dose of trial treatment. The trial is registered with ClinicalTrials.gov (NCT06579105) and clinicaltrials.eu (2024-512562-34-00) and is completed. FINDINGS: From Oct 8, 2024, to June 6, 2025, 863 individuals were screened for study inclusion, 457 were excluded as they did not meet the inclusion criteria or met the exclusion criteria, 406 were enrolled and randomly assigned to one of the eight treatment groups, and 404 participants received at least one dose of trial treatment. Among those who received at least one dose of trial treatment, mean (SD) baseline characteristics were: age 58·4 years (10·7); HbA of 7·9% (0·9); bodyweight of 99·8 kg (22·1); and BMI of 34·9 kg/m (7·5). Of 404 participants, 168 (42%) of participants were female and 236 (58%) were male; 280 (69%) were White. At week 26, the mean change from baseline in HbA ranged between -0·91% (95% CI -1·25 to -0·58; 5 mg elecoglipron) and -1·88% (-2·23 to -1·53; 75 mg elecoglipron with every 2-week dose-escalation step) compared with -0·15% (-0·42 to 0·12) with placebo. Adverse events were reported by 63% (24 of 38 in the 5 mg group and 39 of 62 in the 15 mg group) to 87% (33 of 38 in 75 mg every 4-week dose escalation) of participants across elecoglipron doses compared with 63% (45 of 71) in the placebo group. The most common adverse events were gastrointestinal, including nausea, constipation, diarrhoea, and vomiting. INTERPRETATION: Once-daily oral elecoglipron showed reductions in glycaemia and a safety and tolerability profile consistent with the GLP-1 receptor agonist class at a similar phase of development, supporting continued development with phase 3 trials for people living with type 2 diabetes. FUNDING: AstraZeneca.
Multiple long-term conditions (MLTC or multimorbidity) are increasing in global prevalence and represent a growing burden for individuals and health-care systems. Grouping cardiometabolic MLTC can be justified because ae...Multiple long-term conditions (MLTC or multimorbidity) are increasing in global prevalence and represent a growing burden for individuals and health-care systems. Grouping cardiometabolic MLTC can be justified because aetiological antecedents and risk factors are often shared, and similar therapeutic approaches can have positive effects on the prevention, treatment, and delayed progression of many of the constituent conditions. In this Series paper, we focus on interventions for the prevention and management of cardiometabolic MLTC, under the broad headings of population-level, individual-level, and system-level interventions. Population-level public health measures such as educational, fiscal, regulatory, and environmental policies, and population-level screening and early detection can result in improved risk factor identification and control, although evidence that they reduce incidence and progression of cardiometabolic MLTC is more scarce. At an individual level, lifestyle interventions and pharmacotherapeutics can reduce the incidence and progression of cardiometabolic MLTC and provide effective treatment. Together with pharmacotherapeutic strategies, approaches to improve medicines management could help to optimise clinical outcomes in those living with cardiometabolic MLTC. System-level solutions, including integrated models of care and care continuity, provide opportunities to better address the holistic needs of people living with cardiometabolic MLTC. Together, combinations of multilevel approaches are required.