The Lancet

Merryn Voysey,Sue Ann Costa Clemens,Shabir A Madhi,Lily Y Weckx,Pedro M Folegatti,Parvinder K Aley,Brian Angus,Vicky L Baillie,Shaun L Barnabas,Qasim E Bhorat,Sagida Bibi,Carmen Briner,Paola Cicconi,Elizabeth A Clutterbuck,Andrea M Collins,Clare L Cutland,Thomas C Darton,Keertan Dheda,Christina Dold,Christopher J A Duncan,Katherine R W Emary,Katie J Ewer,Amy Flaxman,Lee Fairlie,Saul N Faust,Shuo Feng,Daniela M Ferreira,Adam Finn,Eva Galiza,Anna L Goodman,Catherine M Green,Christopher A Green,Melanie Greenland,Catherine Hill,Helen C Hill,Ian Hirsch,Alane Izu,Daniel Jenkin,Carina C D Joe,Simon Kerridge,Anthonet Koen,Gaurav Kwatra,Rajeka Lazarus,Vincenzo Libri,Patrick J Lillie,Natalie G Marchevsky,Richard P Marshall,Ana V A Mendes,Eveline P Milan,Angela M Minassian,Alastair McGregor,Yama F Mujadidi,Anusha Nana,Sherman D Padayachee,Daniel J Phillips,Ana Pittella,Emma Plested,Katrina M Pollock,Maheshi N Ramasamy,Adam J Ritchie,Hannah Robinson,Alexandre V Schwarzbold,Andrew Smith,Rinn Song,Matthew D Snape,Eduardo Sprinz,Rebecca K Sutherland,Emma C Thomson,M Estée T?r?k,Mark Toshner,David P J Turner,Johan Vekemans,Tonya L Villafana,Thomas White,Christopher J Williams,Alexander D Douglas,Adrian V S Hill,Teresa Lambe,Sarah C Gilbert,Andrew J Pollardon behalf of the Oxford COVID Vaccine Trial Group

doi : 10.1016/S0140-6736(21)00432-3

ARTICLES| VOLUME 397, ISSUE 10277, P881-891, MARCH 06, 2021

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Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study

Anthony R Mato,Nirav N Shah,Wojciech Jurczak,Chan Y Cheah,John M Pagel,Jennifer A Woyach,Bita Fakhri,Toby A Eyre,Nicole Lamanna,Manish R Patel,Alvaro Alencar,Ewa Lech-Maranda,William G Wierda,Catherine C Coombs,James N Gerson,Paolo Ghia,Steven Le Gouill,David John Lewis,Suchitra Sundaram,Jonathon B Cohen,Ian W Flinn,Constantine S Tam,Minal A Barve,Bryone Kuss,Justin Taylor,Omar Abdel-Wahab,Stephen J Schuster,M Lia Palomba,Katharine L Lewis,Lindsey E Roeker,Matthew S Davids,Xuan Ni Tan,Timothy S Fenske,Johan Wallin,Donald E Tsai,Nora C Ku,Edward Zhu,Jessica Chen,Ming Yin,Binoj Nair,Kevin Ebata,Narasimha Marella,Jennifer R Brown,Michael Wang

doi : 10.1016/S0140-6736(21)00224-5

ARTICLES| VOLUME 397, ISSUE 10277, P892-901, MARCH 06, 2021

Covalent Bruton's tyrosine kinase (BTK) inhibitors are efficacious in multiple B-cell malignancies, but patients discontinue these agents due to resistance and intolerance. We evaluated the safety and efficacy of pirtobrutinib (working name; formerly known as LOXO-305), a highly selective, reversible BTK inhibitor, in these patients.

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Diagnosis of non-consensus transient ischaemic attacks with focal, negative, and non-progressive symptoms: population-based validation by investigation and prognosis

Maria A Tuna,Peter M Rothwellon behalf of the Oxford Vascular Study

doi : 10.1016/S0140-6736(20)31961-9

ARTICLES| VOLUME 397, ISSUE 10277, P902-912, MARCH 06, 2021

Diagnosis of transient ischaemic attacks (TIAs) can be difficult. There is consensus on classic symptoms (eg, motor weakness, dysphasia, hemianopia, monocular visual loss) but no consensus on several monosymptomatic events with sudden-onset, non-progressive, focal negative symptoms (eg, isolated diplopia, dysarthria, vertigo, ataxia, sensory loss, and bilateral visual disturbance), with much variation in investigation and treatment.

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Deficiency of adenosine deaminase 2 diagnosed at 65 years of age

Gaëlle Bourgeois,Mael Richard,Marie Danset,Laurent Pérard,Anne-Laure Breton,Emilie Berthoux

doi : 10.1016/S0140-6736(20)32660-X

CLINICAL PICTURE| VOLUME 397, ISSUE 10277, P913, MARCH 06, 2021

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Anxiety disorders

Brenda WJH Penninx,Daniel S Pine,Emily A Holmes,Andreas Reif

doi : 10.1016/S0140-6736(21)00359-7

SEMINAR| VOLUME 397, ISSUE 10277, P914-927, MARCH 06, 2021

Anxiety disorders form the most common group of mental disorders and generally start before or in early adulthood. Core features include excessive fear and anxiety or avoidance of perceived threats that are persistent and impairing. Anxiety disorders involve dysfunction in brain circuits that respond to danger. Risk for anxiety disorders is influenced by genetic factors, environmental factors, and their epigenetic relations. Anxiety disorders are often comorbid with one another and with other mental disorders, especially depression, as well as with somatic disorders. Such comorbidity generally signifies more severe symptoms, greater clinical burden, and greater treatment difficulty. Reducing the large burden of disease from anxiety disorders in individuals and worldwide can be best achieved by timely, accurate disease detection and adequate treatment administration, scaling up of treatments when needed. Evidence-based psychotherapy (particularly cognitive behavioural therapy) and psychoactive medications (particularly serotonergic compounds) are both effective, facilitating patients' choices in therapeutic decisions. Although promising, no enduring preventive measures are available, and, along with frequent therapy resistance, clinical needs remain unaddressed. Ongoing research efforts tackle these problems, and future efforts should seek individualised, more effective approaches for treatment with precision medicine.

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Improving lung health in low-income and middle-income countries: from challenges to solutions

Jamilah Meghji,Kevin Mortimer,Alvar Agusti,Brian W Allwood,Innes Asher,Eric D Bateman,Karen Bissell,Charlotte E Bolton,Andrew Bush,Bartolome Celli,Chen-Yuan Chiang,Alvaro A Cruz,Anh-Tuan Dinh-Xuan,Asma El Sony,Kwun M Fong,Paula I Fujiwara,Mina Gaga,Luis Garcia-Marcos,David M G Halpin,John R Hurst,Shamanthi Jayasooriya,Ajay Kumar,Maria V Lopez-Varela,Refiloe Masekela,Bertrand H Mbatchou Ngahane,Maria Montes de Oca,Neil Pearce,Helen K Reddel,Sundeep Salvi,Sally J Singh,Cherian Varghese,Claus F Vogelmeier,Paul Walker,Heather J Zar,Guy B Marks

doi : 10.1016/S0140-6736(21)00458-X

REVIEW| VOLUME 397, ISSUE 10277, P928-940, MARCH 06, 2021

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

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