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Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-09-28 Catherine M Broome, Vickie McDonald, Yoshitaka Miyakawa, Monica Carpenedo, David J Kuter, Hanny Al-Samkari, James B Bussel, Marie Godar, Jaume Ayguasanosa, Kristof De Beuf, Francesco Rodeghiero, Marc Michel, Adrian Newland
Background Primary immune thrombocytopenia is an autoimmune disorder mediated partly by platelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional symptoms. Efgartigimod, a first-in-class novel human IgG1 Fc fragment, binds the neonatal Fc receptor with high affinity and thus reduces serum IgG concentrations, including autoantibodies. The objective of this study was to evaluate
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Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial Lancet (IF 168.9) Pub Date : 2023-09-19 Akimichi Morita, Bruce Strober, A David Burden, Siew Eng Choon, Milan J Anadkat, Slaheddine Marrakchi, Tsen-Fang Tsai, Kenneth B Gordon, Diamant Thaçi, Min Zheng, Na Hu, Thomas Haeufel, Christian Thoma, Mark G Lebwohl
Background Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention. Methods This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and
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Role of preoperative in-hospital delay on appendiceal perforation while awaiting appendicectomy (PERFECT): a Nordic, pragmatic, open-label, multicentre, non-inferiority, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-09-14 Karoliina Jalava, Ville Sallinen, Hanna Lampela, Hanna Malmi, Ingeborg Steinholt, Knut Magne Augestad, Ari Leppäniemi, Panu Mentula
Background Appendicectomy remains the standard treatment for appendicitis. No international consensus exists on the surgical urgency for acute uncomplicated appendicitis, and recommendations vary from surgery without delay to surgery within 24 h. Longer in-hospital delay has been thought to increase the risk of perforation and further morbidity. Therefore, we aimed to compare the rate of appendiceal
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NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-09-11 Zev A Wainberg, Davide Melisi, Teresa Macarulla, Roberto Pazo Cid, Sreenivasa R Chandana, Christelle De La Fouchardière, Andrew Dean, Igor Kiss, Woo Jin Lee, Thorsten O Goetze, Eric Van Cutsem, A Scott Paulson, Tanios Bekaii-Saab, Shubham Pant, Richard A Hubner, Zhimin Xiao, Huanyu Chen, Fawzi Benzaghou, Eileen M O'Reilly
Background Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods NAPOLI 3 was a randomised, open-label, phase 3 study conducted at 187 community and academic sites
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Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-09-08 Arshad M Khanani, Sunil S Patel, Giovanni Staurenghi, Ramin Tadayoni, Carl J Danzig, David A Eichenbaum, Jason Hsu, Charles C Wykoff, Jeffrey S Heier, David R Lally, Jordi Monés, Jared S Nielsen, Veeral S Sheth, Peter K Kaiser, Julie Clark, Liansheng Zhu, Hersh Patel, Justin Tang, Dhaval Desai, Glenn J Jaffe, Edward Ysasaga
Background Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. Methods GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals
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Home-based monitoring of ovulation to time frozen embryo transfers in the Netherlands (Antarctica-2): an open-label, nationwide, randomised, non-inferiority trial Lancet (IF 168.9) Pub Date : 2023-09-04 Tjitske Zaat, Jan-Peter de Bruin, Mariëtte Goddijn, Marchien van Baal, Sofie Benneheij, Monique Brandes, Frank Broekmans, Astrid Cantineau, Ben Cohlen, Jeroen van Disseldorp, Susanne Gielen, Eva Groenewoud, Arne van Heusden, Eugenie Kaaijk, Carolien Koks, Corry de Koning, Nicole Klijn, Paul van der Linden, Petra Manger, Lobke Moolenaar, Femke Mol
Background The growing field of assisted reproductive techniques, including frozen-thawed embryo transfer (FET), should lead the way to the best sustainable health care without compromising pregnancy chances. Correct timing of FET is crucial to allow implantation of the thawed embryo. Nowadays, timing based on hospital-controlled monitoring of ovulation in the natural cycle of a woman is the preferred
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Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study Lancet (IF 168.9) Pub Date : 2023-08-31 Raj R Makkar, Samir Kapadia, Tarun Chakravarty, Robert J Cubeddu, Tsuyoshi Kaneko, Paul Mahoney, Dhairya Patel, Aakriti Gupta, Wen Cheng, Susheel Kodali, Deepak L Bhatt, Michael J Mack, Martin B Leon, Vinod H Thourani
Background With increasing numbers of patients undergoing transcatheter aortic valve replacement (TAVR), data on management of failed TAVR, including repeat TAVR procedure, are needed. The aim of this study was to assess the safety and efficacy of redo-TAVR in a national registry. Methods This study included all consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology
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Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial Lancet (IF 168.9) Pub Date : 2023-08-27 Tiffany Patterson, Gavin D Perkins, Alexander Perkins, Tim Clayton, Richard Evans, Matthew Dodd, Steven Robertson, Karen Wilson, Adam Mellett-Smith, Rachael T Fothergill, Paul McCrone, Miles Dalby, Philip MacCarthy, Sam Firoozi, Iqbal Malik, Roby Rakhit, Ajay Jain, Jerry P Nolan, Simon R Redwood, , Mamas Mamas
Background The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. Methods ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial
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Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials Lancet (IF 168.9) Pub Date : 2023-08-26 Uwe Zeymer, Anne Freund, Matthias Hochadel, Petr Ostadal, Jan Belohlavek, Richard Rokyta, Steffen Massberg, Stefan Brunner, Enzo Lüsebrink, Marcus Flather, David Adlam, Kris Bogaerts, Amerjeet Banning, Manel Sabaté, Ibrahim Akin, Alexander Jobs, Steffen Schneider, Steffen Desch, Holger Thiele
Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate
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Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial Lancet (IF 168.9) Pub Date : 2023-08-25 David Conen, Michael Ke Wang, Ekaterine Popova, Matthew T V Chan, Giovanni Landoni, Juan P Cata, Cara Reimer, Sean R McLean, Sadeesh K Srinathan, Juan Carlos Trujillo Reyes, Ascension Martín Grande, Anna Gonzalez Tallada, Daniel I Sessler, Edith Fleischmann, Barbara Kabon, Luca Voltolini, Patrícia Cruz, Donna E Maziak, Laura Gutiérrez-Soriano, William F McIntyre, Jeremy S. Poppers
Background Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. Methods COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing
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Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials Lancet (IF 168.9) Pub Date : 2023-08-25 Charles B Majoie, Fabiano Cavalcante, Jan Gralla, Pengfei Yang, Johannes Kaesmacher, Kilian M Treurniet, Manon Kappelhof, Bernard Yan, Kentaro Suzuki, Yongwei Zhang, Fengli Li, Masafumi Morimoto, Lei Zhang, Zhongrong Miao, Leon A Rinkel, Jiacheng Huang, Toshiaki Otsuka, Shouchun Wang, Stephen Davis, Christophe Cognard, Margaux Lefebvre
Background Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic
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Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-08-23 Hope S Rugo, Aditya Bardia, Frederik Marmé, Javier Cortés, Peter Schmid, Delphine Loirat, Olivier Trédan, Eva Ciruelos, Florence Dalenc, Patricia Gómez Pardo, Komal L Jhaveri, Rosemary Delaney, Theresa Valdez, Hao Wang, Monica Motwani, Oh Kyu Yoon, Wendy Verret, Sara M Tolaney
Background Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2–) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall
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Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-08-24 Bruce L Wilkoff, Gerasimos Filippatos, Christophe Leclercq, Michael R Gold, Ahmad S Hersi, Kengo Kusano, Wilfried Mullens, G Michael Felker, Charan Kantipudi, Mikhael F El-Chami, Vidal Essebag, Bertrand Pierre, Francois Philippon, Francisco Perez-Gil, Eugene S Chung, Juan Sotomonte, Stanley Tung, Balbir Singh, Babak Bozorgnia, Satish Goel, David Birnie
Background Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical
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Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study Lancet (IF 168.9) Pub Date : 2023-08-17 Alexandre Loupy, Valentin Goutaudier, Alessia Giarraputo, Fariza Mezine, Erwan Morgand, Blaise Robin, Karen Khalil, Sapna Mehta, Brendan Keating, Amy Dandro, Anaïs Certain, Pierre-Louis Tharaux, Navneet Narula, Renaud Tissier, Sébastien Giraud, Thierry Hauet, Harvey I Pass, Aurélie Sannier, Ming Wu, Adam Griesemer, Robert A Montgomery
Background Cross-species immunological incompatibilities have hampered pig-to-human xenotransplantation, but porcine genome engineering recently enabled the first successful experiments. However, little is known about the immune response after the transplantation of pig kidneys to human recipients. We aimed to precisely characterise the early immune responses to the xenotransplantation using a multimodal
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Participation rate and yield of two home-based screening methods to detect increased albuminuria in the general population in the Netherlands (THOMAS): a prospective, randomised, open-label implementation study Lancet (IF 168.9) Pub Date : 2023-08-16 Dominique van Mil, Lyanne M Kieneker, Birgitte Evers-Roeten, Marc H M Thelen, Hanne de Vries, Marc H Hemmelder, Annemiek Dorgelo, Ronald W van Etten, Hiddo J L Heerspink, Ron T Gansevoort
Background Chronic kidney disease (CKD) has a rising global prevalence and is expected to become the fifth leading cause of death by 2030. Increased albuminuria defines the early stages of CKD and is among the strongest risk factors for progressive CKD and cardiovascular disease. The value of population screening for albuminuria to detect CKD in an early phase has yet to be studied. We aimed to evaluate
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Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial Lancet (IF 168.9) Pub Date : 2023-08-16 Raymond Hang Wun Li, Sue Seen Tsing Lo, Kristina Gemzell-Danielsson, Carol Ho Yi Fong, Pak Chung Ho, Ernest Hung Yu Ng
Background Levonorgestrel, a standard drug for emergency contraception (EC), is not effective if administered post-ovulation. A cyclo-oxygenase inhibitor could contribute synergistic effects. We investigated whether a single 40 mg oral dose of piroxicam as co-treatment with levonorgestrel improved emergency contraceptive efficacy. Methods This was a randomised double-blind placebo-controlled trial
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Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial Lancet (IF 168.9) Pub Date : 2023-08-14 Richard Lafayette, Jens Kristensen, Andrew Stone, Jürgen Floege, Vladimir Tesař, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Heather N Reich, Brad H Rovin, Jonathan Barratt
Background IgA nephropathy is a chronic immune-mediated kidney disease and a major cause of kidney failure worldwide. The gut mucosal immune system is implicated in its pathogenesis, and Nefecon is a novel, oral, targeted-release formulation of budesonide designed to act at the gut mucosal level. We present findings from the 2-year, phase 3 NefIgArd trial of Nefecon in patients with IgA nephropathy
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Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study Lancet (IF 168.9) Pub Date : 2023-08-09 Miquel Serra-Burriel, Adrià Juanola, Feliu Serra-Burriel, Maja Thiele, Isabel Graupera, Elisa Pose, Guillem Pera, Ivica Grgurevic, Llorenç Caballeria, Salvatore Piano, Laurens van Kleef, Mathias Reichert, Dominique Roulot, Juan M Pericàs, Jörn M Schattenberg, Emmanuel A Tsochatztis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosario Hernández, Jordi Hoyo, Tracey Wildsmith
Background Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals
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Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-08-10 Simon D Kyle, A Niroshan Siriwardena, Colin A Espie, Yaling Yang, Stavros Petrou, Emma Ogburn, Nargis Begum, Leonie F Maurer, Barbara Robinson, Caroline Gardner, Victoria Lee, Stephanie Armstrong, Julie Pattinson, Sam Mort, Eleanor Temple, Victoria Harris, Ly-Mee Yu, Peter Bower, Paul Aveyard
Background Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. Methods We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction
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Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial Lancet (IF 168.9) Pub Date : 2023-08-08 Anurag Bhargava, Madhavi Bhargava, Ajay Meher, Andrea Benedetti, Banurekha Velayutham, G Sai Teja, Basilea Watson, Ganesh Barik, Rajeev Ranjan Pathak, Ranjit Prasad, Rakesh Dayal, Adarsh Kibballi Madhukeshwar, Vineet Chadha, Madhukar Pai, Rajendra Joshi, Dick Menzies, Soumya Swaminathan
Background In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. Methods In this field-based
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Cause-specific mortality by county, race, and ethnicity in the USA, 2000–19: a systematic analysis of health disparities Lancet (IF 168.9) Pub Date : 2023-08-03
Background Large disparities in mortality exist across racial–ethnic groups and by location in the USA, but the extent to which racial–ethnic disparities vary by location, or how these patterns vary by cause of death, is not well understood. We aimed to estimate age-standardised mortality by racial–ethnic group, county, and cause of death and describe the intersection between racial–ethnic and place-based
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Adjuvant everolimus after surgery for renal cell carcinoma (EVEREST): a double-blind, placebo-controlled, randomised, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-07-28 Christopher W Ryan, Catherine M Tangen, Elisabeth I Heath, Mark N Stein, Maxwell V Meng, Ajjai S Alva, Sumanta K Pal, Igor Puzanov, Joseph I Clark, Toni K Choueiri, Neeraj Agarwal, Robert G Uzzo, Naomi B Haas, Timothy W Synold, Melissa Plets, Ulka N Vaishampayan, Brian M Shuch, Ian M Thompson, Primo N Lara
Background Patients undergoing resection of renal cell carcinoma are at risk of disease relapse. We evaluated the effectiveness of the mammalian target of rapamycin inhibitor everolimus administered after surgery. Methods In this randomised, double-blind, phase 3 trial, we enrolled adults with histologically confirmed renal cell carcinoma who had undergone a full surgical resection and were at intermediate-high
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Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-07-26 Patricia Pozo-Rosich, Jessica Ailani, Messoud Ashina, Peter J Goadsby, Richard B Lipton, Uwe Reuter, Hua Guo, Brittany Schwefel, Kaifeng Lu, Ramesh Boinpally, Rosa Miceli, Rosa De Abreu Ferreira, Emily McCusker, Sung Yun Yu, Lawrence Severt, Michelle Finnegan, Joel M Trugman
Background In this study, we aimed to evaluate the efficacy, safety, and tolerability of atogepant for the preventive treatment of chronic migraine. Methods We did this randomised, double-blind, placebo-controlled, phase 3 trial at 142 clinical research sites across the USA, the UK, Canada, China, Czech Republic, Denmark, France, Germany, Italy, Japan, South Korea, Poland, Russia, Spain, Sweden, and
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The risk of sexual transmission of HIV in individuals with low-level HIV viraemia: a systematic review Lancet (IF 168.9) Pub Date : 2023-07-22 Laura N Broyles, Robert Luo, Debi Boeras, Lara Vojnov
Background The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications, especially in resource-limited settings that use alternatives to plasma-based viral load testing. This Article summarises the evidence related to sexual transmission of HIV at varying HIV viral load levels to inform messaging
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Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study Lancet (IF 168.9) Pub Date : 2023-07-24 Shukui Qin, Stephen L Chan, Shanzhi Gu, Yuxian Bai, Zhenggang Ren, Xiaoyan Lin, Zhendong Chen, Weidong Jia, Yongdong Jin, Yabing Guo, Xiaohua Hu, Zhiqiang Meng, Jun Liang, Ying Cheng, Jianping Xiong, Hong Ren, Fang Yang, Wei Li, Yajin Chen, Yong Zeng, Gontran Verset
Background Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted
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Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial Lancet (IF 168.9) Pub Date : 2023-07-18 Joe Y Chang, Steven H Lin, Wenli Dong, Zhongxing Liao, Saumil J Gandhi, Carl M Gay, Jianjun Zhang, Stephen G Chun, Yasir Y Elamin, Frank V Fossella, George Blumenschein, Tina Cascone, Xiuning Le, Jenny V Pozadzides, Anne Tsao, Vivek Verma, James W Welsh, Aileen B Chen, Mehmet Altan, Reza J Mehran, John V Heymach
Background Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised
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Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-07-18 Frank R Lin, James R Pike, Marilyn S Albert, Michelle Arnold, Sheila Burgard, Theresa Chisolm, David Couper, Jennifer A Deal, Adele M Goman, Nancy W Glynn, Theresa Gmelin, Lisa Gravens-Mueller, Kathleen M Hayden, Alison R Huang, David Knopman, Christine M Mitchell, Thomas Mosley, James S Pankow, Nicholas S Reed, Victoria Sanchez, Josef Coresh
Background Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. Methods The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70–84 years with untreated hearing loss
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Adjuvant immunotherapy with nivolumab versus observation in completely resected Merkel cell carcinoma (ADMEC-O): disease-free survival results from a randomised, open-label, phase 2 trial Lancet (IF 168.9) Pub Date : 2023-07-11 Jürgen C Becker, Selma Ugurel, Ulrike Leiter, Friedegund Meier, Ralf Gutzmer, Sebastian Haferkamp, Lisa Zimmer, Elisabeth Livingstone, Thomas K Eigentler, Axel Hauschild, Felix Kiecker, Jessica C Hassel, Peter Mohr, Michael Fluck, Ioannis Thomas, Marlene Garzarolli, Imke Grimmelmann, Konstantin Drexler, Alexandra N Spillner, Sebastian Eckhardt, Bastian Schilling
Background Merkel cell carcinoma (MCC) is an immunogenic but aggressive skin cancer. Even after complete resection and radiation, relapse rates are high. PD-1 and PD-L1 checkpoint inhibitors showed clinical benefit in advanced MCC. We aimed to assess efficacy and safety of adjuvant immune checkpoint inhibition in completely resected MCC (ie, a setting without an established systemic standard-of-care
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First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study Lancet (IF 168.9) Pub Date : 2023-07-06 Siow Ming Lee, Christian Schulz, Kumar Prabhash, Dariusz Kowalski, Aleksandra Szczesna, Baohui Han, Achim Rittmeyer, Toby Talbot, David Vicente, Raffaele Califano, Diego Cortinovis, Anh Tuan Le, Dingzhi Huang, Geoffrey Liu, Federico Cappuzzo, Jessica Reyes Contreras, Martin Reck, Ramon Palmero, Milena Perez Mak, Youyou Hu, Solange Peters
Background Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy
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Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial Lancet (IF 168.9) Pub Date : 2023-07-06 Athimalaipet V Ramanan, Pierre Quartier, Nami Okamoto, Ivan Foeldvari, Alberto Spindler, Šárka Fingerhutová, Jordi Antón, Zhongkai Wang, Gabriella Meszaros, Joana Araújo, Ran Liao, Stuart Keller, Hermine I Brunner, Nicolino Ruperto
Background Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis. Methods This phase 3, randomised, double-blind, placebo-controlled, withdrawal
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Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial Lancet (IF 168.9) Pub Date : 2023-07-03 Gerrit Burkhardt, Ulrike Kumpf, Alexander Crispin, Stephan Goerigk, Elisabeth Andre, Christian Plewnia, Bettina Brendel, Andreas Fallgatter, Berthold Langguth, Mohamed Abdelnaim, Tobias Hebel, Claus Normann, Lukas Frase, Peter Zwanzger, Julia Diemer, Thomas Kammer, Carlos Schönfeldt-Lecuona, Daniel Kamp, Malek Bajbouj, Nora Behler, Frank Padberg
Background Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with
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The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019 Lancet (IF 168.9) Pub Date : 2023-06-29
Background Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge
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Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report Lancet (IF 168.9) Pub Date : 2023-06-29 Muhammad M Mohiuddin, Avneesh K Singh, Linda Scobie, Corbin E Goerlich, Alison Grazioli, Kapil Saharia, Claire Crossan, Allen Burke, Cinthia Drachenberg, Cihan Oguz, Tianshu Zhang, Billeta Lewis, Alena Hershfeld, Faith Sentz, Ivan Tatarov, Sarah Mudd, Gheorghe Braileanu, Kathryn Rice, John F Paolini, Kent Bondensgaard, Bartley P Griffith
Background A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome. Methods Physiological and
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Planned delivery or expectant management for late preterm pre-eclampsia in low-income and middle-income countries (CRADLE-4): a multicentre, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-06-29 Alice Beardmore-Gray, Nicola Vousden, Paul T Seed, Bellington Vwalika, Sebastian Chinkoyo, Victor Sichone, Alexander B Kawimbe, Umesh Charantimath, Geetanjali Katageri, Mrutyunjaya B Bellad, Laxmikant Lokare, Kasturi Donimath, Shailaja Bidri, Shivaprasad Goudar, Jane Sandall, Lucy C Chappell, Andrew H Shennan
Background Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to evaluate whether planned delivery between 34+ 0 and 36+ 6 weeks’ gestation can reduce maternal mortality and morbidity without increasing perinatal complications in India and Zambia. Methods In this parallel-group, multicentre
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Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study Lancet (IF 168.9) Pub Date : 2023-06-24 Juan P Frias, Stanley Hsia, Sarah Eyde, Rong Liu, Xiaosu Ma, Manige Konig, Christof Kazda, Kieren J Mather, Axel Haupt, Edward Pratt, Deborah Robins
Background Orforglipron, an oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, is in development for type 2 diabetes and obesity. We assessed the efficacy and safety of orforglipron versus placebo or dulaglutide in participants with type 2 diabetes. Methods In this 26-week, phase 2, double-blind, randomised, multicentre study, participants were recruited from 45 centres (private clinics
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Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial Lancet (IF 168.9) Pub Date : 2023-06-28 Caitlin M P Jones, Richard O Day, Bart W Koes, Jane Latimer, Chris G Maher, Andrew J McLachlan, Laurent Billot, Sana Shan, Chung-Wei Christine Lin
Background Opioid analgesics are commonly used for acute low back pain and neck pain, but supporting efficacy data are scarce. We aimed to investigate the efficacy and safety of a judicious short course of an opioid analgesic for acute low back pain and neck pain. Methods OPAL was a triple-blinded, placebo-controlled randomised trial that recruited adults (aged ≥18 years) presenting to one of 157 primary
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Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-06-26 Filip K Knop, Vanita R Aroda, Ruben D do Vale, Thomas Holst-Hansen, Peter N Laursen, Julio Rosenstock, Domenica M Rubino, W Timothy Garvey
Background We assessed the efficacy and safety of the oral glucagon-like peptide-1 analogue, semaglutide 50 mg, taken once per day versus placebo for the treatment of overweight or obesity in adults without type 2 diabetes. Methods This randomised, double-blind, placebo-controlled, phase 3, superiority trial enrolled adults with a BMI of at least 30 kg/m2, or at least 27 kg/m2 with bodyweight-related
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Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-06-26 W Timothy Garvey, Juan P Frias, Ania M Jastreboff, Carel W le Roux, Naveed Sattar, Diego Aizenberg, Huzhang Mao, Shuyu Zhang, Nadia N Ahmad, Mathijs C Bunck, Imane Benabbad, Xiaotian M Zhang
Background Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes. Methods This phase 3, double-blind, randomised, placebo-controlled
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Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial Lancet (IF 168.9) Pub Date : 2023-06-26 Vanita R Aroda, Jens Aberle, Lars Bardtrum, Erik Christiansen, Filip K Knop, Sanaz Gabery, Sue D Pedersen, John B Buse
Background Once-daily oral semaglutide is an effective type 2 diabetes treatment. We aimed to investigate a new formulation of oral semaglutide at higher investigational doses versus the approved 14 mg dose in adults with inadequately controlled type 2 diabetes. Methods This global, multicentre, randomised, double-blind, phase 3b trial, carried out at 177 sites in 14 countries, enrolled adults with
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Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA Lancet (IF 168.9) Pub Date : 2023-06-26 Julio Rosenstock, Juan Frias, Ania M Jastreboff, Yu Du, Jitong Lou, Sirel Gurbuz, Melissa K Thomas, Mark L Hartman, Axel Haupt, Zvonko Milicevic, Tamer Coskun
Background According to current consensus guidelines for type 2 diabetes management, bodyweight management is as important as attaining glycaemic targets. Retatrutide, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, showed clinically meaningful glucose-lowering and bodyweight-lowering efficacy in a phase 1 study. We aimed
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Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial Lancet (IF 168.9) Pub Date : 2023-06-23 Juan P Frias, Srikanth Deenadayalan, Lars Erichsen, Filip K Knop, Ildiko Lingvay, Stanislava Macura, Chantal Mathieu, Sue D Pedersen, Melanie Davies
Background Combining the GLP-1 receptor agonist semaglutide with the long-acting amylin analogue cagrilintide has weight-loss benefits; the impact on glycated haemoglobin (HbA1c) is unknown. This trial assessed the efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes. Methods This 32-week, multicentre, double-blind, phase 2 trial was
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Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 Lancet (IF 168.9) Pub Date : 2023-06-22
Background Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021
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High-dose dual-antibiotic loaded cement for hip hemiarthroplasty in the UK (WHiTE 8): a randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-06-21 Nickil R Agni, Matthew L Costa, Juul Achten, Nicholas Peckham, Susan J Dutton, May Ee Png, Mike R Reed
Background Hip fracture is the most common injury requiring treatment in hospital. Controversy exists regarding the use of antibiotic loaded bone cement in hip fractures treated with hemiarthroplasty. We aimed to compare the rate of deep surgical site infection in patients receiving high-dose dual-antibiotic loaded cement versus standard care single-antibiotic loaded cement. Methods We included people
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Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium Lancet (IF 168.9) Pub Date : 2023-06-20 Monica S Thakar, Brent R Logan, Jennifer M Puck, Elizabeth A Dunn, Rebecca H Buckley, Morton J Cowan, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Sung-Yun Pai, Jennifer Heimall, Sharat Chandra, Christen L Ebens, Deepak Chellapandian, Olatundun Williams, Lauri M Burroughs, Blachy Davila Saldana, Ahmad Rayes, Lisa M Madden, Shanmuganathan Chandrakasan, Luigi D Notarangelo
Background Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for
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Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial Lancet (IF 168.9) Pub Date : 2023-06-18 Michael G Collins, Magid A Fahim, Elaine M Pascoe, Carmel M Hawley, David W Johnson, Julie Varghese, Laura E Hickey, Philip A Clayton, Kathryn B Dansie, Rachael C McConnochie, Liza A Vergara, Charani Kiriwandeniya, Donna Reidlinger, Peter F Mount, Laurence Weinberg, Colin J McArthur, P Toby Coates, Zoltan H Endre, David Goodman, Kirsten Howard, Claire Scherring
Background Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that
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Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial Lancet (IF 168.9) Pub Date : 2023-06-15 Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip, , Ayham Al-Zoebi
Background Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular
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Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study Lancet (IF 168.9) Pub Date : 2023-06-15 Arvind Dasari, Sara Lonardi, Rocio Garcia-Carbonero, Elena Elez, Takayuki Yoshino, Alberto Sobrero, James Yao, Pilar García-Alfonso, Judit Kocsis, Antonio Cubillo Gracian, Andrea Sartore-Bianchi, Taroh Satoh, Violaine Randrian, Jiri Tomasek, Geoff Chong, Andrew Scott Paulson, Toshiki Masuishi, Jeremy Jones, Tibor Csőszi, Chiara Cremolini, Cathy Eng
Background There is a paucity of effective systemic therapy options for patients with advanced, chemotherapy-refractory colorectal cancer. We aimed to evaluate the efficacy and safety of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3, in patients with heavily pretreated metastatic colorectal cancer. Methods We conducted
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Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-06-12 Martina Schneider, Marivic Narciso-Abraham, Sandra Hadl, Robert McMahon, Sebastian Toepfer, Ulrike Fuchs, Romana Hochreiter, Annegret Bitzer, Karin Kosulin, Julian Larcher-Senn, Robert Mader, Katrin Dubischar, Oliver Zoihsl, Juan-Carlos Jaramillo, Susanne Eder-Lingelbach, Vera Buerger, Nina Wressnigg
Background VLA1553 is a live-attenuated vaccine candidate for active immunisation and prevention of disease caused by chikungunya virus. We report safety and immunogenicity data up to day 180 after vaccination with VLA1553. Methods This double-blind, multicentre, randomised, phase 3 trial was done in 43 professional vaccine trial sites in the USA. Eligible participants were healthy volunteers aged
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6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Lancet (IF 168.9) Pub Date : 2023-06-12 Chaolin Huang, Lixue Huang, Yeming Wang, Xia Li, Lili Ren, Xiaoying Gu, Liang Kang, Li Guo, Min Liu, Xing Zhou, Jianfeng Luo, Zhenghui Huang, Shengjin Tu, Yue Zhao, Li Chen, Decui Xu, Yanping Li, Caihong Li, Lu Peng, Yong Li, Bin Cao
Background The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. Methods We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged
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Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-06-10 Uwe Platzbecker, Matteo Giovanni Della Porta, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Jake Shortt, David Valcarcel, Anna Jonasova, Sophie Dimicoli-Salazar, Ing Soo Tiong, Chien-Chin Lin, Jiahui Li, Jennie Zhang, Ana Carolina Giuseppi, Sandra Kreitz, Veronika Pozharskaya, Karen L Keeperman, Shelonitda Rose, Jeevan K Shetty, Sheida Hayati, Guillermo Garcia-Manero
Background Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified
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Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial Lancet (IF 168.9) Pub Date : 2023-06-08 Charlotte E Coles, Joanne S Haviland, Anna M Kirby, Clare L Griffin, Mark A Sydenham, Jenny C Titley, Indrani Bhattacharya, A Murray Brunt, H Y Charlie Chan, Ellen M Donovan, David J Eaton, Marie Emson, Penny Hopwood, Monica L Jefford, Sara V Lightowlers, Elinor J Sawyer, Isabel Syndikus, Yat M Tsang, Nicola I Twyman, John R Yarnold, Judith M Bliss
Background A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. Methods IMPORT HIGH is a phase 3
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Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1–2 study Lancet (IF 168.9) Pub Date : 2023-06-06 Tanya Siddiqi, David G Maloney, Saad S Kenderian, Danielle M Brander, Kathleen Dorritie, Jacob Soumerai, Peter A Riedell, Nirav N Shah, Rajneesh Nath, Bita Fakhri, Deborah M Stephens, Shuo Ma, Tatyana Feldman, Scott R Solomon, Stephen J Schuster, Serena K Perna, Sherilyn A Tuazon, San-San Ou, Eniko Papp, Leanne Peiser, William G Wierda
Background Patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma for whom treatment has failed with both Bruton tyrosine kinase (BTK) inhibitor and venetoclax have few treatment options and poor outcomes. We aimed to evaluate the efficacy and safety of lisocabtagene maraleucel (liso-cel) at the recommended phase 2 dose in patients with relapsed or refractory
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Burden of disease attributable to unsafe drinking water, sanitation, and hygiene in domestic settings: a global analysis for selected adverse health outcomes Lancet (IF 168.9) Pub Date : 2023-06-05 Jennyfer Wolf, Richard B Johnston, Argaw Ambelu, Benjamin F Arnold, Robert Bain, Michael Brauer, Joe Brown, Bethany A Caruso, Thomas Clasen, John M Colford, Joanna Esteves Mills, Barbara Evans, Matthew C Freeman, Bruce Gordon, Gagandeep Kang, Claudio F Lanata, Kate O Medlicott, Annette Prüss-Ustün, Christopher Troeger, Sophie Boisson, Oliver Cumming
Background Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development
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Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial Lancet (IF 168.9) Pub Date : 2023-06-05 Sumanta Kumar Pal, Laurence Albiges, Piotr Tomczak, Cristina Suárez, Martin H Voss, Guillermo de Velasco, Jad Chahoud, Anastasia Mochalova, Giuseppe Procopio, Hakim Mahammedi, Friedemann Zengerling, Chan Kim, Takahiro Osawa, Martín Angel, Suyasha Gupta, Omara Khan, Guillaume Bergthold, Bo Liu, Melania Kalaitzidou, Mahrukh Huseni, Toni K Choueiri
Background Immune checkpoint inhibitors are the standard of care for first-line treatment of patients with metastatic renal cell carcinoma, yet optimised treatment of patients whose disease progresses after these therapies is unknown. The aim of this study was to determine whether adding atezolizumab to cabozantinib delayed disease progression and prolonged survival in patients with disease progression
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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 168.9) 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 168.9) 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 168.9) 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 168.9) 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 168.9) 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 168.9) 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