The Lancet

The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure.

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Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

RECOVERY Collaborative Group

doi : 10.1016/S0140-6736(21)00676-0

ARTICLES| VOLUME 397, ISSUE 10285, P1637-1645, MAY 01, 2021

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

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Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study

Eleftheria Vasileiou,Colin R Simpson,Ting Shi,Steven Kerr,Utkarsh Agrawal,Ashley Akbari,Stuart Bedston,Jillian Beggs,Declan Bradley,Antony Chuter,Simon de Lusignan,Annemarie B Docherty,David Ford,FD Richard Hobbs,Mark Joy,Srinivasa Vittal Katikireddi,James Marple,Colin McCowan,Dylan McGagh,Jim McMenamin,Emily Moore,Josephine LK Murray,Jiafeng Pan,Lewis Ritchie,Syed Ahmar Shah,Sarah Stock,Fatemeh Torabi,Ruby SM Tsang,Rachael Wood,Mark Woolhouse,Chris Robertson,Aziz Sheikh

doi : 10.1016/S0140-6736(21)00677-2

ARTICLES| VOLUME 397, ISSUE 10285, P1646-1657, MAY 01, 2021

The BNT162b2 mRNA (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.

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Bilateral superior ophthalmic vein thrombosis, ischaemic stroke, and immune thrombocytopenia after ChAdOx1 nCoV-19 vaccination

Antonios Bayas,Martina Menacher,Monika Christ,Lars Behrens,Andreas Rank,Markus Naumann

doi : 10.1016/S0140-6736(21)00872-2

CLINICAL PICTURE| VOLUME 397, ISSUE 10285, E11, MAY 01, 2021

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Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss

Siobhan Quenby,Ioannis D Gallos,Rima K Dhillon-Smith,Marcelina Podesek,Mary D Stephenson,Joanne Fisher,Jan J Brosens,Jane Brewin,Rosanna Ramhorst,Emma S Lucas,Rajiv C McCoy,Robert Anderson,Shahd Daher,Lesley Regan,Maya Al-Memar,Tom Bourne,David A MacIntyre,Raj Rai,Ole B Christiansen,Mayumi Sugiura-Ogasawara,Joshua Odendaal,Adam J Devall,Phillip R Bennett,Stavros Petrou,Arri Coomarasamy

doi : 10.1016/S0140-6736(21)00682-6

SERIES|MISCARRIAGE| VOLUME 397, ISSUE 10285, P1658-1667, MAY 01, 2021

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5–18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3–11·4%), two miscarriages is 1·9% (1·8–2·1%), and three or more miscarriages is 0·7% (0·5–0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.

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Sporadic miscarriage: evidence to provide effective care

Arri Coomarasamy,Ioannis D Gallos,Argyro Papadopoulou,Rima K Dhillon-Smith,Maya Al-Memar,Jane Brewin,Ole B Christiansen,Mary D Stephenson,Olufemi T Oladapo,Chandrika N Wijeyaratne,Rachel Small,Phillip R Bennett,Lesley Regan,Mariëtte Goddijn,Adam J Devall,Tom Bourne,Jan J Brosens,Siobhan Quenby

doi : 10.1016/S0140-6736(21)00683-8

SERIES|MISCARRIAGE| VOLUME 397, ISSUE 10285, P1668-1674, MAY 01, 2021

The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units.

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Recurrent miscarriage: evidence to accelerate action

Arri Coomarasamy,Rima K Dhillon-Smith,Argyro Papadopoulou,Maya Al-Memar,Jane Brewin,Vikki M Abrahams,Abha Maheshwari,Ole B Christiansen,Mary D Stephenson,Mariëtte Goddijn,Olufemi T Oladapo,Chandrika N Wijeyaratne,Debra Bick,Hassan Shehata,Rachel Small,Phillip R Bennett,Lesley Regan,Raj Rai,Tom Bourne,Rajinder Kaur,Oonagh Pickering,Jan J Brosens,Adam J Devall,Ioannis D Gallos,Siobhan Quenby

doi : 10.1016/S0140-6736(21)00681-4

SERIES|MISCARRIAGE| VOLUME 397, ISSUE 10285, P1675-1682, MAY 01, 2021

Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.

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