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Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-06-04 Neeraj Agarwal, Arun A Azad, Joan Carles, Andre P Fay, Nobuaki Matsubara, Daniel Heinrich, Cezary Szczylik, Ugo De Giorgi, Jae Young Joung, Peter C C Fong, Eric Voog, Robert J Jones, Neal D Shore, Curtis Dunshee, Stefanie Zschäbitz, Jan Oldenburg, Xun Lin, Cynthia G Healy, Nicola Di Santo, Fabian Zohren, Karim Fizazi
Background Co-inhibition of poly(ADP-ribose) polymerase (PARP) and androgen receptor activity might result in antitumour efficacy irrespective of alterations in DNA damage repair genes involved in homologous recombination repair (HRR). We aimed to compare the efficacy and safety of talazoparib (a PARP inhibitor) plus enzalutamide (an androgen receptor blocker) versus enzalutamide alone in patients
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Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial Lancet (IF 202.731) Pub Date : 2023-06-01 Siobhan Quenby, Katie Booth, Louise Hiller, Arri Coomarasamy, Paulien G de Jong, Eva N Hamulyák, Luuk J Scheres, Thijs F van Haaps, Lauren Ewington, Shreeya Tewary, Mariëtte Goddijn, Saskia Middeldorp,
Background Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population. Methods The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26)
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The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial Lancet (IF 202.731) Pub Date : 2023-05-25 Lu Ma, Xin Hu, Lili Song, Xiaoying Chen, Menglu Ouyang, Laurent Billot, Qiang Li, Alejandra Malavera, Xi Li, Paula Muñoz-Venturelli, Asita de Silva, Nguyen Huy Thang, Kolawole W Wahab, Jeyaraj D Pandian, Mohammad Wasay, Octavio M Pontes-Neto, Carlos Abanto, Antonio Arauz, Haiping Shi, Guanghai Tang, Huy Thai
Background Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes
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Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF): a randomised clinical trial Lancet (IF 202.731) Pub Date : 2023-05-20 Jasper J Brugts, Sumant P Radhoe, Pascal R D Clephas, Dilan Aydin, Marco W F van Gent, Mariusz K Szymanski, Michiel Rienstra, Mieke H van den Heuvel, Carlos A da Fonseca, Gerard C M Linssen, C Jan Willem Borleffs, Eric Boersma, Folkert W Asselbergs, Arend Mosterd, Hans-Peter Brunner-La Rocca, Rudolf A de Boer
Background The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system. Methods MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible
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Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial Lancet (IF 202.731) Pub Date : 2023-05-17 Janet A Wilson, James O'Hara, Tony Fouweather, Tara Homer, Deborah D Stocken, Luke Vale, Catherine Haighton, Nikki Rousseau, Rebecca Wilson, Lorraine McSweeney, Scott Wilkes, Jill Morrison, Kenneth MacKenzie, Kim Ah-See, Sean Carrie, Claire Hopkins, Nicola Howe, Musheer Hussain, Hisham Mehanna, Christopher Raine, M Dawn Teare
Background Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. Methods
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Safety, effectiveness, and cost-effectiveness of immediate versus delayed sequential bilateral cataract surgery in the Netherlands (BICAT-NL study): a multicentre, non-inferiority, randomised controlled trial Lancet (IF 202.731) Pub Date : 2023-05-15 Lindsay Spekreijse, Rob Simons, Bjorn Winkens, Frank van den Biggelaar, Carmen Dirksen, Marjolijn Bartels, Ronald de Crom, Oege Goslings, Maurits Joosse, Jocelyn Kasanardjo, Peter Lansink, Theodorus Ponsioen, Nic Reus, Jan Schouten, Rudy Nuijts
Background In an ageing population, efficiency improvements are required to assure future accessibility of cataract care. We aim to address remaining knowledge gaps by evaluating the safety, effectiveness, and cost-effectiveness of immediate sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS). We hypothesised that ISBCS is non-inferior to DSBCS
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Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients Lancet (IF 202.731) Pub Date : 2023-05-05 Natalie Staplin, Alejandro de la Sierra, Luis M Ruilope, Jonathan R Emberson, Ernest Vinyoles, Manuel Gorostidi, Gema Ruiz-Hurtado, Julián Segura, Colin Baigent, Bryan Williams
Background Ambulatory blood pressure provides a more comprehensive assessment than clinic blood pressure, and has been reported to better predict health outcomes than clinic or home pressure. We aimed to examine associations of clinic and 24-h ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of primary care patients referred for assessment of hypertension. Methods
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Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial Lancet (IF 202.731) Pub Date : 2023-05-05 Chantal Mathieu, Björg Ásbjörnsdóttir, Harpreet S Bajaj, Wendy Lane, Ana Laura S A Matos, Sreenivasa Murthy, Karolina Stachlewska, Julio Rosenstock
Background Insulin icodec (icodec) is a basal insulin analogue suitable for once-weekly dosing. ONWARDS 4 aimed to assess the efficacy and safety of once-weekly icodec compared with once-daily insulin glargine U100 (glargine U100) in individuals with long-standing type 2 diabetes on a basal-bolus regimen. Methods In this 26-week, phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority
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Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK Lancet (IF 202.731) Pub Date : 2023-05-05 Nathalie Conrad, Shivani Misra, Jan Y Verbakel, Geert Verbeke, Geert Molenberghs, Peter N Taylor, Justin Mason, Naveed Sattar, John J V McMurray, Iain B McInnes, Kamlesh Khunti, Geraldine Cambridge
Background A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region
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Cognitive functional therapy with or without movement sensor biofeedback versus usual care for chronic, disabling low back pain (RESTORE): a randomised, controlled, three-arm, parallel group, phase 3, clinical trial Lancet (IF 202.731) Pub Date : 2023-05-02 Peter Kent, Terry Haines, Peter O'Sullivan, Anne Smith, Amity Campbell, Robert Schutze, Stephanie Attwell, J P Caneiro, Robert Laird, Kieran O'Sullivan, Alison McGregor, Jan Hartvigsen, Den-Ching A Lee, Alistair Vickery, Mark Hancock
Background Low back pain is the leading cause of years lived with disability globally, but most interventions have only short-lasting, small to moderate effects. Cognitive functional therapy (CFT) is an individualised approach that targets unhelpful pain-related cognitions, emotions, and behaviours that contribute to pain and disability. Movement sensor biofeedback might enhance treatment effects.
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Effectiveness of handwashing with soap for preventing acute respiratory infections in low-income and middle-income countries: a systematic review and meta-analysis Lancet (IF 202.731) Pub Date : 2023-04-27 Ian Ross, Sarah Bick, Philip Ayieko, Robert Dreibelbis, Jennyfer Wolf, Matthew C Freeman, Elizabeth Allen, Michael Brauer, Oliver Cumming
Background Acute respiratory infection (ARI) is a leading cause of morbidity and mortality globally, with 83% of ARI mortality occurring in low-income and middle-income countries (LMICs) before the COVID-19 pandemic. We aimed to estimate the effect of interventions promoting handwashing with soap on ARI in LMICs. Methods In our systematic review and meta-analysis, we searched MEDLINE, Embase, Web of
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Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study Lancet (IF 202.731) Pub Date : 2023-04-24 Adèle de Masson, Marie Beylot-Barry, Caroline Ram-Wolff, Jean-Baptiste Mear, Stéphane Dalle, Michel d'Incan, Saskia Ingen-Housz-Oro, Corentin Orvain, Julie Abraham, Olivier Dereure, Amandine Charbonnier, Jérôme Cornillon, Christine Longvert, Stéphane Barete, Serge Boulinguez, Ewa Wierzbicka-Hainaut, François Aubin, Marie-Thérèse Rubio, Marc Bernard, Aline Schmidt-Tanguy, Jacques-Olivier Bay
Background Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage
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Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-04-25 Harry P Erba, Pau Montesinos, Hee-Je Kim, Elżbieta Patkowska, Radovan Vrhovac, Pavel Žák, Po-Nan Wang, Tsvetomir Mitov, James Hanyok, Yasser Mostafa Kamel, Jaime E Connolly Rohrbach, Li Liu, Aziz Benzohra, Arnaud Lesegretain, Jorge Cortes, Alexander E Perl, Mikkael A Sekeres, Hervé Dombret, Sergio Amadori, Jianxiang Wang, Richard F Schlenk
Background Patients with acute myeloid leukaemia (AML) positive for internal tandem duplication (ITD) mutations of FLT3 have poor outcomes. Quizartinib, an oral, highly potent, selective, type 2 FLT3 inhibitor, plus chemotherapy showed antitumour activity with an acceptable safety profile in patients with FLT3-ITD-positive newly diagnosed AML. The aim of the study was to compare the effect of quizartinib
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A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-04-25 Andrew W Bradbury, Catherine A Moakes, Matthew Popplewell, Lewis Meecham, Gareth R Bate, Lisa Kelly, Ian Chetter, Athanasios Diamantopoulos, Arul Ganeshan, Jack Hall, Simon Hobbs, Kim Houlind, Hugh Jarrett, Suzanne Lockyer, Jonas Malmstedt, Jai V Patel, Smitaa Patel, S Tawqeer Rashid, Athanasios Saratzis, Gemma Slinn, Jonathan J Deeks
Background Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic
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Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial Lancet (IF 202.731) Pub Date : 2023-04-21 Sant-Rayn Pasricha, Martin N Mwangi, Ernest Moya, Ricardo Ataide, Glory Mzembe, Rebecca Harding, Truwah Zinenani, Leila M Larson, Ayse Y Demir, William Nkhono, Jobiba Chinkhumba, Julie A Simpson, Danielle Clucas, William Stones, Sabine Braat, Kamija S Phiri
Background Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. Methods In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13–26 weeks' gestation
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Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial Lancet (IF 202.731) Pub Date : 2023-04-21 Ornella Verrastro, Simona Panunzi, Lidia Castagneto-Gissey, Andrea De Gaetano, Erminia Lembo, Esmeralda Capristo, Caterina Guidone, Giulia Angelini, Francesco Pennestrì, Luca Sessa, Fabio Maria Vecchio, Laura Riccardi, Maria Assunta Zocco, Ivo Boskoski, James R Casella-Mariolo, Pierluigi Marini, Maurizio Pompili, Giovanni Casella, Enrico Fiori, Francesco Rubino, Geltrude Mingrone
Background Observational studies suggest that bariatric–metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. Methods We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants
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Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population-based, prospective birth cohort study Lancet (IF 202.731) Pub Date : 2023-04-20 Christian Rosas-Salazar, Tatiana Chirkova, Tebeb Gebretsadik, James D Chappell, R Stokes Peebles, William D Dupont, Samadhan J Jadhao, Peter J Gergen, Larry J Anderson, Tina V Hartert
Background Early-life severe respiratory syncytial virus (RSV) infection has been associated with the onset of childhood wheezing illnesses. However, the relationship between RSV infection during infancy and the development of childhood asthma is unclear. We aimed to assess the association between RSV infection during infancy and childhood asthma. Methods INSPIRE is a large, population-based, birth
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Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-04-20 Fabrice André, Yeon Hee Park, Sung-Bae Kim, Toshimi Takano, Seock-Ah Im, Giuliano Borges, Joao Paulo Lima, Sercan Aksoy, Joaquin Gavila Gregori, Michelino De Laurentiis, Giampaolo Bianchini, Rebecca Roylance, Yasuo Miyoshi, Anne Armstrong, Rajni Sinha, Manuel Ruiz Borrego, Elgene Lim, Johannes Ettl, Rinat Yerushalmi, Flora Zagouri, Ian Krop
Background In the single-arm, phase 2 DESTINY-Breast01 trial, trastuzumab deruxtecan showed robust activity in patients with HER2-positive metastatic breast cancer who were refractory or resistant to trastuzumab emtansine; a population with scarce effective treatments. In DESTINY-Breast02, we aimed to compare the efficacy and safety of trastuzumab deruxtecan with treatment of physician's choice in
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Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-04-16 Robin Kate Kelley, Makoto Ueno, Changhoon Yoo, Richard S Finn, Junji Furuse, Zhenggang Ren, Thomas Yau, Heinz-Josef Klümpen, Stephen L Chan, Masato Ozaka, Chris Verslype, Mohamed Bouattour, Joon Oh Park, Olga Barajas, Uwe Pelzer, Juan W Valle, Li Yu, Usha Malhotra, Abby B Siegel, Julien Edeline, Haitao Zhao
Background Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor
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Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-04-15 Kohei Shitara, Florian Lordick, Yung-Jue Bang, Peter Enzinger, David Ilson, Manish A Shah, Eric Van Cutsem, Rui-Hua Xu, Giuseppe Aprile, Jianming Xu, Joseph Chao, Roberto Pazo-Cid, Yoon-Koo Kang, Jianning Yang, Diarmuid Moran, Pranob Bhattacharya, Ahsan Arozullah, Jung Wook Park, Mok Oh, Jaffer A Ajani
Background Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. We report the results of the SPOTLIGHT trial, which investigated the efficacy and safety of first-line
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Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials Lancet (IF 202.731) Pub Date : 2023-04-14
Background Anthracycline–taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline
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Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b–3 trial Lancet (IF 202.731) Pub Date : 2023-04-14 Brett King, Xingqi Zhang, Walter Gubelin Harcha, Jacek C Szepietowski, Jerry Shapiro, Charles Lynde, Natasha A Mesinkovska, Samuel H Zwillich, Lynne Napatalung, Dalia Wajsbrot, Rana Fayyad, Amy Freyman, Debanjali Mitra, Vivek Purohit, Rodney Sinclair, Robert Wolk
Background Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. Methods In this randomised, double-blind, multicentre, phase 2b–3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata
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Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial Lancet (IF 202.731) Pub Date : 2023-04-13
Background Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This randomised, controlled, open-label platform trial (Randomised
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The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial Lancet (IF 202.731) Pub Date : 2023-04-06 Ram K Chandyo, Ingrid Kvestad, Manjeswori Ulak, Suman Ranjitkar, Mari Hysing, Merina Shrestha, Catherine Schwinger, Adrian McCann, Per M Ueland, Sudha Basnet, Laxman Shrestha, Tor A Strand
Background Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment. Methods In this community-based, double-blind, placebo-controlled trial, we randomly
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Specific causes of excess late mortality and association with modifiable risk factors among survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort Lancet (IF 202.731) Pub Date : 2023-04-05 Stephanie B Dixon, Qi Liu, Eric J Chow, Kevin C Oeffinger, Paul C Nathan, Rebecca M Howell, Wendy M Leisenring, Matthew J Ehrhardt, Kirsten K Ness, Kevin R Krull, Ann C Mertens, Melissa M Hudson, Leslie L Robison, Yutaka Yasui, Gregory T Armstrong
Background 5-year survival after childhood cancer does not fully describe life-years lost due to childhood cancer because there are a large number of deaths occurring beyond 5-years (late mortality) related to cancer and cancer treatment. Specific causes of health-related (non-recurrence, non-external) late mortality and risk reduction through modifiable lifestyle and cardiovascular risk factors are
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Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial Lancet (IF 202.731) Pub Date : 2023-04-01 Hiddo J L Heerspink, Jai Radhakrishnan, Charles E Alpers, Jonathan Barratt, Stewart Bieler, Ulysses Diva, Jula Inrig, Radko Komers, Alex Mercer, Irene L Noronha, Michelle N Rheault, William Rote, Brad Rovin, Howard Trachtman, Hernán Trimarchi, Muh Geot Wong, Vlado Perkovic
Background Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods PROTECT is an international, randomised, double-blind, active-controlled study, being conducted
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Clinical outcomes of uninterrupted embryo culture with or without time-lapse-based embryo selection versus interrupted standard culture (SelecTIMO): a three-armed, multicentre, double-blind, randomised controlled trial Lancet (IF 202.731) Pub Date : 2023-03-30 D C Kieslinger, C G Vergouw, L Ramos, B Arends, M H J M Curfs, E Slappendel, E H Kostelijk, M H E C Pieters, D Consten, M O Verhoeven, D E Besselink, F Broekmans, B J Cohlen, J M J Smeenk, S Mastenbroek, C H de Koning, Y M van Kasteren, E Moll, J van Disseldorp, E A Brinkhuis, C B Lambalk
Background Time-lapse monitoring is increasingly used in fertility laboratories to culture and select embryos for transfer. This method is offered to couples with the promise of improving pregnancy chances, even though there is currently insufficient evidence for superior clinical results. We aimed to evaluate whether a potential improvement by time-lapse monitoring is caused by the time-lapse-based
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Endovascular treatment versus no endovascular treatment after 6–24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-03-29 Susanne G H Olthuis, F Anne V Pirson, Florentina M E Pinckaers, Wouter H Hinsenveld, Daan Nieboer, Angelique Ceulemans, Robrecht R M M Knapen, M M Quirien Robbe, Olvert A Berkhemer, Marianne A A van Walderveen, Geert J Lycklama à Nijeholt, Maarten Uyttenboogaart, Wouter J Schonewille, P Matthijs van der Sluijs, Lennard Wolff, Henk van Voorst, Alida A Postma, Stefan D Roosendaal, Anouk van der Hoorn
Background Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6–24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). Methods MR CLEAN-LATE was a multicentre
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Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial Lancet (IF 202.731) Pub Date : 2023-03-29 Guy Young, Alok Srivastava, Kaan Kavakli, Cecil Ross, Jameela Sathar, Chur-Woo You, Huyen Tran, Jing Sun, Runhui Wu, Stacey Poloskey, Zhiying Qiu, Salim Kichou, Shauna Andersson, Baisong Mei, Savita Rangarajan
Background Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors. Methods This multicentre, randomised, open-label phase 3 study
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Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis Lancet (IF 202.731) Pub Date : 2023-03-23 Thomas J Bollyky, Emma Castro, Aleksandr Y Aravkin, Kayleigh Bhangdia, Jeremy Dalos, Erin N Hulland, Samantha Kiernan, Amy Lastuka, Theresa A McHugh, Samuel M Ostroff, Peng Zheng, Hamza Tariq Chaudhry, Elle Ruggiero, Isabella Turilli, Christopher Adolph, Joanne O Amlag, Bree Bang-Jensen, Ryan M Barber, Austin Carter, Cassidy Chang, Joseph L Dieleman
Background The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had
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Evaluating the impact of alcohol minimum unit pricing on deaths and hospitalisations in Scotland: a controlled interrupted time series study Lancet (IF 202.731) Pub Date : 2023-03-20 Grant M A Wyper, Daniel F Mackay, Catriona Fraser, Jim Lewsey, Mark Robinson, Clare Beeston, Lucie Giles
Background Since May 1, 2018, every alcoholic drink sold in Scotland has had minimum unit pricing (MUP) of £0·50 per unit. Previous studies have indicated that the introduction of this policy reduced alcohol sales by 3%. We aimed to assess whether this has led to reductions in alcohol-attributable deaths and hospitalisations. Methods Study outcomes, wholly attributable to alcohol consumption, were
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Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial Lancet (IF 202.731) Pub Date : 2023-03-16 Roland Tschismarov, Pierre Van Damme, Clara Germain, Ilse De Coster, Mathieu Mateo, Stephanie Reynard, Alexandra Journeaux, Yvonne Tomberger, Kanchanamala Withanage, Denise Haslwanter, Katherine Terler, Sabrina Schrauf, Matthias Müllner, Erich Tauber, Katrin Ramsauer, Sylvain Baize
Background Lassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV). Methods This first-in-human phase 1 trial—consisting of an open-label dose-escalation stage and an observer-blinded, randomised, placebo-controlled treatment stage—was conducted at
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Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study Lancet (IF 202.731) Pub Date : 2023-03-13 Samuel Lederman, Faith D Ottery, Antonio Cano, Nanette Santoro, Marla Shapiro, Petra Stute, Rebecca C Thurston, Marci English, Catherine Franklin, Misun Lee, Genevieve Neal-Perry
Background Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomotor symptoms due to menopause. This study investigated
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Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus–diphtheria–acellular pertussis vaccine: a randomised, double-blind, phase 2b trial Lancet (IF 202.731) Pub Date : 2023-03-09 Cheryl Keech, Vicki E Miller, Barbara Rizzardi, Christopher Hoyle, Melinda J Pryor, Jonathan Ferrand, Ken Solovay, Marcel Thalen, Stephanie Noviello, Peter Goldstein, Andrew Gorringe, Breeze Cavell, Qiushui He, Alex-Mikael Barkoff, Keith Rubin, Camille Locht
Background Bordetella pertussis epidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent B pertussis infection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus–diphtheria–acellular pertussis vaccine (Tdap). Methods In this double-blind
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Effect of monthly intermittent preventive treatment with dihydroartemisinin–piperaquine with and without azithromycin versus monthly sulfadoxine–pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial Lancet (IF 202.731) Pub Date : 2023-03-10 Mwayiwawo Madanitsa, Hellen C Barsosio, Daniel T R Minja, George Mtove, Reginald A Kavishe, James Dodd, Queen Saidi, Eric D Onyango, Kephas Otieno, Duolao Wang, Ulla Ashorn, Jenny Hill, Crispin Mukerebe, Samwel Gesase, Omari A Msemo, Victor Mwapasa, Kamija S Phiri, Kenneth Maleta, Nigel Klein, Pascal Magnussen, Feiko O ter Kuile
Background Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin–piperaquine is more effective than IPTp with sulfadoxine–pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine–pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin–piperaquine, alone or combined with
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Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: a national birth cohort study Lancet (IF 202.731) Pub Date : 2023-03-07 James Peter Allinson, Nishi Chaturvedi, Andrew Wong, Imran Shah, Gavin Christopher Donaldson, Jadwiga Anna Wedzicha, Rebecca Hardy
Background Lower respiratory tract infections (LRTIs) in early childhood are known to influence lung development and lifelong lung health, but their link to premature adult death from respiratory disease is unclear. We aimed to estimate the association between early childhood LRTI and the risk and burden of premature adult mortality from respiratory disease. Methods This longitudinal observational
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Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials Lancet (IF 202.731) Pub Date : 2023-03-06 Paul M Ridker, Deepak L Bhatt, Aruna D Pradhan, Robert J Glynn, Jean G MacFadyen, Steven E Nissen
Background Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, when people are treated with intensive statin therapy, the relative contributions of inflammation and hyperlipidaemia to the risk of future cardiovascular events might change, which has implications for the choice of adjunctive cardiovascular therapeutics. We aimed to evaluate the relative importance
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Electronic nudges to increase influenza vaccination uptake in Denmark: a nationwide, pragmatic, registry-based, randomised implementation trial Lancet (IF 202.731) Pub Date : 2023-03-05 Niklas Dyrby Johansen, Muthiah Vaduganathan, Ankeet S Bhatt, Simin Gharib Lee, Daniel Modin, Brian L Claggett, Erica L Dueger, Sandrine I Samson, Matthew M Loiacono, Lars Køber, Scott D Solomon, Pradeesh Sivapalan, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Palle Valentiner-Branth, Tyra Grove Krause, Tor Biering-Sørensen
Background Influenza vaccination rates remain suboptimal despite effectiveness in preventing influenza infection and related complications. We investigated whether behavioural nudges, delivered via a governmental electronic letter system, would increase influenza vaccination uptake among older adults in Denmark. Methods We did a nationwide, pragmatic, registry-based, cluster-randomised implementation
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Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial Lancet (IF 202.731) Pub Date : 2023-03-05 Roberto Diletti, Wijnand K den Dekker, Johan Bennett, Carl E Schotborgh, Rene van der Schaaf, Manel Sabaté, Raúl Moreno, Koen Ameloot, Rutger van Bommel, Daniele Forlani, Bert van Reet, Giovanni Esposito, Maurits T Dirksen, Willem P T Ruifrok, Bert R C Everaert, Carlos Van Mieghem, Jacob J Elscot, Paul Cummins, Mattie Lenzen, Salvatore Brugaletta, Nicolas M Van Mieghem
Background In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. Methods This prospective, open-label, non-inferiority, randomised trial was done
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Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies Lancet (IF 202.731) Pub Date : 2023-03-02 William J Sandborn, Séverine Vermeire, Laurent Peyrin-Biroulet, Marla C Dubinsky, Julian Panes, Andres Yarur, Timothy Ritter, Filip Baert, Stefan Schreiber, Sheldon Sloan, Fabio Cataldi, Kevin Shan, Christopher J Rabbat, Michael Chiorean, Douglas C Wolf, Bruce E Sands, Geert D'Haens, Silvio Danese, Martina Goetsch, Brian G Feagan
Background Etrasimod, a once-daily, oral, sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P receptor subtypes 1, 4, and 5, with no detectable activity on S1P2,3, is in development for the treatment of immune-mediated diseases, including ulcerative colitis. In these two phase 3 trials, we aimed to evaluate the safety and efficacy of etrasimod in adult patients with moderately
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Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial Lancet (IF 202.731) Pub Date : 2023-03-02 Jiang He, Nanxiang Ouyang, Xiaofan Guo, Guozhe Sun, Zhao Li, Jianjun Mu, Dao Wen Wang, Lixia Qiao, Liying Xing, Guocheng Ren, Chunxia Zhao, Ruihai Yang, Zuyi Yuan, Chang Wang, Chuning Shi, Songyue Liu, Wei Miao, Guangxiao Li, Chung-Shiuan Chen, Yingxian Sun, Hua He
Background Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. Methods In this open-label, blinded-endpoint, cluster-randomised
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Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-02-28 Timothy J Craig, Avner Reshef, H Henry Li, Joshua S Jacobs, Jonathan A Bernstein, Henriette Farkas, William H Yang, Erik S G Stroes, Isao Ohsawa, Raffi Tachdjian, Michael E Manning, William R Lumry, Inmaculada Martinez Saguer, Emel Aygören-Pürsün, Bruce Ritchie, Gordon L Sussman, John Anderson, Kimito Kawahata, Yusuke Suzuki, Petra Staubach, Markus Magerl
Background Hereditary angioedema is a rare and potentially life-threatening genetic disease that is associated with kallikrein–kinin system dysregulation. Garadacimab (CSL312), a novel, fully-human monoclonal antibody that inhibits activated factor XII (FXIIa), is being studied for the prevention of hereditary angioedema attacks. The aim of this study was to evaluate the efficacy and safety of once-monthly
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Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I) Lancet (IF 202.731) Pub Date : 2023-02-24 Eric F Morand, Edward M Vital, Michelle Petri, Ronald van Vollenhoven, Daniel J Wallace, Marta Mosca, Richard A Furie, Maria E Silk, Christina L Dickson, Gabriella Meszaros, Bochao Jia, Brenda Crowe, Inmaculada de la Torre, Thomas Dörner
Background Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. The objective of this trial was to evaluate the efficacy and safety
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Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II) Lancet (IF 202.731) Pub Date : 2023-02-24 Michelle Petri, Ian N Bruce, Thomas Dörner, Yoshiya Tanaka, Eric F Morand, Kenneth C Kalunian, Mario H Cardiel, Maria E Silk, Christina L Dickson, Gabriella Meszaros, Lu Zhang, Bochao Jia, Youna Zhao, Conor J McVeigh, Marta Mosca
Background Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. In this Article, we report the evaluation of efficacy and safety of
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Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-02-23 Rui You, You-Ping Liu, Yu-Long Xie, Chao Lin, Chong-Yang Duan, Dong-Ping Chen, Yi Pan, Bin Qi, Xiong Zou, Ling Guo, Jing-Yu Cao, Yi-Nuan Zhang, Zhi-Qiang Wang, Yong-Long Liu, Yan-Feng Ouyang, Kai Wen, Qi Yang, Ruo-Qi Xie, Hui-Feng Li, Xiao-Tong Duan, Ming-Yuan Chen
Background Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. Methods
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Mpox in people with advanced HIV infection: a global case series Lancet (IF 202.731) Pub Date : 2023-02-21 Oriol Mitjà, Andrea Alemany, Michael Marks, Jezer I Lezama Mora, Juan Carlos Rodríguez-Aldama, Mayara Secco Torres Silva, Ever Arturo Corral Herrera, Brenda Crabtree-Ramirez, José Luis Blanco, Nicolo Girometti, Valentina Mazzotta, Aniruddha Hazra, Macarena Silva, Juan José Montenegro-Idrogo, Kelly Gebo, Jade Ghosn, María Fernanda Peña Vázquez, Eduardo Matos Prado, Uche Unigwe, Judit Villar-García,
Background People living with HIV have accounted for 38–50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of
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Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis Lancet (IF 202.731) Pub Date : 2023-02-16
Background Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine
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Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial Lancet (IF 202.731) Pub Date : 2023-02-09 Yongjun Wang, Shuya Li, Yuesong Pan, Hao Li, Mark W Parsons, Bruce C V Campbell, Lee H Schwamm, Marc Fisher, Fengyuan Che, Hongguo Dai, Deyang Li, Runhui Li, Junhai Wang, Yilong Wang, Xingquan Zhao, Zixiao Li, Huaguang Zheng, Yunyun Xiong, Xia Meng, , Zhihua Long
Background There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. Methods In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic
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Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-02-09 Robert J Motzer, Paul Russo, Viktor Grünwald, Yoshihiko Tomita, Bogdan Zurawski, Omi Parikh, Sebastiano Buti, Philippe Barthélémy, Jeffrey C Goh, Dingwei Ye, Alejo Lingua, Jean-Baptiste Lattouf, Laurence Albigès, Saby George, Brian Shuch, Jeffrey Sosman, Michael Staehler, Sergio Vázquez Estévez, Burcin Simsek, Julia Spiridigliozzi, Axel Bex
Background Effective adjuvant therapy for patients with resected localised renal cell carcinoma represents an unmet need, with surveillance being the standard of care. We report results from part A of a phase 3, randomised trial that aimed to assess the efficacy and safety of adjuvant nivolumab plus ipilimumab versus placebo. Methods The double-blind, randomised, phase 3 CheckMate 914 trial enrolled
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An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial Lancet (IF 202.731) Pub Date : 2023-02-09 Emel Aygören-Pürsün, Andrea Zanichelli, Danny M Cohn, Mauro Cancian, Roman Hakl, Tamar Kinaciyan, Markus Magerl, Inmaculada Martinez-Saguer, Marcin Stobiecki, Henriette Farkas, Sorena Kiani-Alikhan, Vesna Grivcheva-Panovska, Jonathan A Bernstein, H Henry Li, Hilary J Longhurst, Paul K Audhya, Michael D Smith, Christopher M Yea, Andreas Maetzel, Daniel K Lee, Marcus Maurer
Background Guidelines recommend effective on-demand therapy for all individuals with hereditary angioedema. We aimed to assess the novel oral plasma kallikrein inhibitor, sebetralstat, which is in development, for on-demand treatment of hereditary angioedema attacks. Methods In this two-part phase 2 trial, individuals with type 1 or 2 hereditary angioedema aged 18 years or older were recruited from
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Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis Lancet (IF 202.731) Pub Date : 2023-02-08 Yang Pan, Liang Wang, Zhaomin Feng, Hui Xu, Fu Li, Ying Shen, Daitao Zhang, William J Liu, George F Gao, Quanyi Wang
Background Due to the national dynamic zero-COVID strategy in China, there were no persistent local transmissions of SARS-CoV-2 in Beijing before December, 2022. However, imported cases have been frequently detected over the past 3 years. With soaring growth in the number of COVID-19 cases in China recently, there are concerns that there might be an emergence of novel SARS-CoV-2 variants. Routine surveillance
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Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial Lancet (IF 202.731) Pub Date : 2023-02-07 Adrianus Johannes de Langen, Melissa L Johnson, Julien Mazieres, Anne-Marie C Dingemans, Giannis Mountzios, Miklos Pless, Jürgen Wolf, Martin Schuler, Hervé Lena, Ferdinandos Skoulidis, Yasuto Yoneshima, Sang-We Kim, Helena Linardou, Silvia Novello, Anthonie J van der Wekken, Yuanbin Chen, Solange Peters, Enriqueta Felip, Benjamin J Solomon, Suresh S. Ramalingam, Luis Paz-Ares
Background Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRASG12C. We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRASG12C mutation who had been previously treated with other anticancer drugs. Methods We conducted a randomised, open-label phase 3 trial at 148 centres in 22 countries
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Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials Lancet (IF 202.731) Pub Date : 2023-02-03 Alexa B Kimball, Gregor B E Jemec, Afsaneh Alavi, Ziad Reguiai, Alice B Gottlieb, Falk G Bechara, Carle Paul, Evangelos J Giamarellos Bourboulis, Axel P Villani, Andreas Schwinn, Franziska Ruëff, Larisha Pillay Ramaya, Adam Reich, Ines Lobo, Rodney Sinclair, Thierry Passeron, Antonio Martorell, Pedro Mendes-Bastos, Georgios Kokolakis, Pierre-Andre Becherel, Elisa Muscianisi
Background Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials. Methods SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries
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Cell-free fetal DNA for genetic evaluation in Copenhagen Pregnancy Loss Study (COPL): a prospective cohort study Lancet (IF 202.731) Pub Date : 2023-02-02
Background One in four pregnancies end in a pregnancy loss. Although the effect on couples is well documented, evidence-based treatments and prediction models are absent. Fetal aneuploidy is associated with a higher chance of a next successful pregnancy compared with euploid pregnancy loss in which underlying maternal conditions might be causal. Ploidy diagnostics are therefore advantageous but challenging
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A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study Lancet (IF 202.731) Pub Date : 2023-02-02 Jesse J Swen, Cathelijne H van der Wouden, Lisanne EN Manson, Heshu Abdullah-Koolmees, Kathrin Blagec, Tanja Blagus, Stefan Böhringer, Anne Cambon-Thomsen, Erika Cecchin, Ka-Chun Cheung, Vera HM Deneer, Mathilde Dupui, Magnus Ingelman-Sundberg, Siv Jonsson, Candace Joefield-Roka, Katja S Just, Mats O Karlsson, Lidija Konta, Rudolf Koopmann, Marjolein Kriek, Arjunan Rajasingam
Background The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene
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Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial Lancet (IF 202.731) Pub Date : 2023-02-01 Andrew W Horne, Stephen Tong, Catherine A Moakes, Lee J Middleton, W Colin Duncan, Ben W Mol, Lucy H R Whitaker, Davor Jurkovic, Arri Coomarasamy, Natalie Nunes, Tom Holland, Fiona Clarke, Ann M Doust, Jane P Daniels
Background Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus
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Cooling cities through urban green infrastructure: a health impact assessment of European cities Lancet (IF 202.731) Pub Date : 2023-01-31 Tamara Iungman, Marta Cirach, Federica Marando, Evelise Pereira Barboza, Sasha Khomenko, Pierre Masselot, Marcos Quijal-Zamorano, Natalie Mueller, Antonio Gasparrini, José Urquiza, Mehdi Heris, Meelan Thondoo, Mark Nieuwenhuijsen
Background High ambient temperatures are associated with many health effects, including premature mortality. The combination of global warming due to climate change and the expansion of the global built environment mean that the intensification of urban heat islands (UHIs) is expected, accompanied by adverse effects on population health. Urban green infrastructure can reduce local temperatures. We
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Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study Lancet (IF 202.731) Pub Date : 2023-01-26
Background Janus kinase (JAK) inhibitors approved for myelofibrosis provide spleen and symptom improvements but do not meaningfully improve anaemia. Momelotinib, a first-in-class inhibitor of activin A receptor type 1 as well as JAK1 and JAK2, has shown symptom, spleen, and anaemia benefits in myelofibrosis. We aimed to confirm the differentiated clinical benefits of momelotinib versus the active comparator
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Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial Lancet (IF 202.731) Pub Date : 2023-01-26
Background WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy
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The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial Lancet (IF 202.731) Pub Date : 2023-01-25 Daren K Heyland, Jayshil Patel, Charlene Compher, Todd W Rice, Danielle E Bear, Zheng-Yii Lee, Victoria C González, Kevin O'Reilly, Racquel Regala, Courtney Wedemire, Miguel Ibarra-Estrada, Christian Stoppe, Luis Ortiz-Reyes, Xuran Jiang, Andrew G Day
Background On the basis of low-quality evidence, international critical care nutrition guidelines recommend a wide range of protein doses. The effect of delivering high-dose protein during critical illness is unknown. We aimed to test the hypothesis that a higher dose of protein provided to critically ill patients would improve their clinical outcomes. Methods This international, investigator-initiated