LancetPub Date : 2024-09-07Epub Date: 2024-08-23DOI: 10.1016/S0140-6736(24)01753-7
Archibong Edem Bassey
{"title":"The health of migrants at the intersection of mpox and HIV.","authors":"Archibong Edem Bassey","doi":"10.1016/S0140-6736(24)01753-7","DOIUrl":"10.1016/S0140-6736(24)01753-7","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LancetPub Date : 2024-09-07Epub Date: 2024-08-30DOI: 10.1016/S0140-6736(24)01643-X
Mikhail N Kosiborod, John Deanfield, Richard Pratley, Barry A Borlaug, Javed Butler, Melanie J Davies, Scott S Emerson, Steven E Kahn, Dalane W Kitzman, Ildiko Lingvay, Kenneth W Mahaffey, Mark C Petrie, Jorge Plutzky, Søren Rasmussen, Cecilia Rönnbäck, Sanjiv J Shah, Subodh Verma, Peter E Weeke, A Michael Lincoff
{"title":"Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.","authors":"Mikhail N Kosiborod, John Deanfield, Richard Pratley, Barry A Borlaug, Javed Butler, Melanie J Davies, Scott S Emerson, Steven E Kahn, Dalane W Kitzman, Ildiko Lingvay, Kenneth W Mahaffey, Mark C Petrie, Jorge Plutzky, Søren Rasmussen, Cecilia Rönnbäck, Sanjiv J Shah, Subodh Verma, Peter E Weeke, A Michael Lincoff","doi":"10.1016/S0140-6736(24)01643-X","DOIUrl":"10.1016/S0140-6736(24)01643-X","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established.</p><p><strong>Methods: </strong>We conducted a post-hoc pooled, participant-level analysis of four randomised, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) to examine the effects of once-weekly subcutaneous semaglutide (2·4 mg in SELECT, STEP-HFpEF, and STEP-HFpEF DM; 1·0 mg in FLOW) on heart failure events. The STEP-HFpEF and STEP-HFpF DM trials enrolled participants with obesity-related HFpEF, the SELECT trial enrolled participants with atherosclerotic cardiovascular disease and overweight or obesity, and the FLOW trial enrolled participants with type 2 diabetes and chronic kidney disease. Hence, for this analysis, we include all participants from the STEP-HFpEF trials and those with an investigator-reported history of HFpEF from SELECT and FLOW. The main outcomes for this analysis were the composite endpoint of time to cardiovascular death or first worsening heart failure event (defined as hospitalisation or urgent visit due to heart failure), time to first worsening heart failure event, and time to cardiovascular death. Efficacy and safety endpoints were analysed with the full analysis set (ie, all participants randomly assigned to treatment, according to the intention-to-treat principle). The SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials are registered at ClinicalTrials.gov, NCT03574597, NCT03819153, NCT04788511, and NCT04916470, respectively, and all are complete.</p><p><strong>Findings: </strong>Across the four trials, 3743 (16·8%) of 22 282 participants had a history of HFpEF (1914 assigned to semaglutide and 1829 assigned to placebo). In this group of participants with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or heart failure events (103 [5·4%] of 1914 in the semaglutide group had events vs 138 [7·5%] of 1829 in the placebo group; hazard ratio [HR] 0·69 [95% CI 0·53-0·89]; p=0·0045). Semaglutide also reduced the risk of worsening heart failure events (54 [2·8%] vs 86 [4·7%]; HR 0·59 [0·41-0·82]; p=0·0019). No significant effect on cardiovascular death alone was seen (59 [3·1%] vs 67 [3·7%]; HR 0·82 [0·57-1·16]; p=0·25). A lower proportion of patients treated with semaglutide had serious adverse events than did those who were treated with placebo (572 [29·9%] vs 708 [38·7%]).</p><p><strong>Interpretation: </strong>In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LancetPub Date : 2024-09-07Epub Date: 2024-08-31DOI: 10.1016/S0140-6736(24)01616-7
Marco Valgimigli, Sung-Jin Hong, Felice Gragnano, Konstantina Chalkou, Anna Franzone, Bruno R da Costa, Usman Baber, Byeong-Keuk Kim, Yangsoo Jang, Shao-Liang Chen, Gregg W Stone, Joo-Yong Hahn, Stephan Windecker, Michael C Gibson, Young Bin Song, Zhen Ge, Pascal Vranckx, Shamir Mehta, Hyeon-Cheol Gwon, Renato D Lopes, George D Dangas, Eùgene P McFadden, Dominick J Angiolillo, Sergio Leonardi, Dik Heg, Paolo Calabrò, Peter Jüni, Roxana Mehran, Myeong-Ki Hong
{"title":"De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials.","authors":"Marco Valgimigli, Sung-Jin Hong, Felice Gragnano, Konstantina Chalkou, Anna Franzone, Bruno R da Costa, Usman Baber, Byeong-Keuk Kim, Yangsoo Jang, Shao-Liang Chen, Gregg W Stone, Joo-Yong Hahn, Stephan Windecker, Michael C Gibson, Young Bin Song, Zhen Ge, Pascal Vranckx, Shamir Mehta, Hyeon-Cheol Gwon, Renato D Lopes, George D Dangas, Eùgene P McFadden, Dominick J Angiolillo, Sergio Leonardi, Dik Heg, Paolo Calabrò, Peter Jüni, Roxana Mehran, Myeong-Ki Hong","doi":"10.1016/S0140-6736(24)01616-7","DOIUrl":"10.1016/S0140-6736(24)01616-7","url":null,"abstract":"<p><strong>Background: </strong>Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation.</p><p><strong>Methods: </strong>A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y<sub>12</sub> inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083).</p><p><strong>Findings: </strong>A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ<sup>2</sup><0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ<sup>2</sup>=0·079) and all-cause death (Kaplan-Meier estimate 0·","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LancetPub Date : 2024-09-07DOI: 10.1016/S0140-6736(24)01447-8
Paul Yang, Laura P Pardon, Allen C Ho, Andreas K Lauer, Dan Yoon, Shannon E Boye, Sanford L Boye, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Malgorzata Swider, Iryna Viarbitskaya, Tomas S Aleman, Mark E Pennesi, Christine N Kay, Kenji P Fujita, Artur V Cideciyan
{"title":"Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.","authors":"Paul Yang, Laura P Pardon, Allen C Ho, Andreas K Lauer, Dan Yoon, Shannon E Boye, Sanford L Boye, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Malgorzata Swider, Iryna Viarbitskaya, Tomas S Aleman, Mark E Pennesi, Christine N Kay, Kenji P Fujita, Artur V Cideciyan","doi":"10.1016/S0140-6736(24)01447-8","DOIUrl":"10.1016/S0140-6736(24)01447-8","url":null,"abstract":"<p><strong>Background: </strong>Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.</p><p><strong>Methods: </strong>15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study. All patients received unilateral subretinal injections of ATSN-101. In the dose-escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1·0 × 10<sup>10</sup> vg/eye (low dose), 3·0 × 10<sup>10</sup> vg/eye (middle dose), and 1·0 × 10<sup>11</sup> vg/eye (high dose). In the dose-expansion phase, one adult cohort (n=3) and one paediatric cohort (n=3) were treated at the high dose. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints included full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also done. Data through the 12-month main study period are reported.</p><p><strong>Findings: </strong>Patients were enrolled between Sept 12, 2019, and May 5, 2022. A total of 68 TEAEs were observed, 56 of which were related to the surgical procedure. No serious TEAE was related to the study drug. Ocular inflammation was mild and reversible with steroid treatment. For patients who received the high dose, mean change in dark-adapted FST was 20·3 decibels (dB; 95% CI 6·6 to 34·0) for treated eyes and 1·1 dB (-3·7 to 5·9) for untreated eyes at month 12 (white stimulus); improvements were first observed at day 28 and persisted over 12 months (p=0·012). Modest improvements in BCVA were also observed (p=0·10). Three of six patients who received the high dose and did the MLMT achieved the maximum score in the treated eye.</p><p><strong>Interpretation: </strong>ATSN-101 is well tolerated 12 months after treatment, with no drug-related serious adverse events. Clinically significant improvements in retinal sensitivity were sustained in patients receiving the high dose.</p><p><strong>Funding: </strong>Atsena Therapeutics.</p>","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LancetPub Date : 2024-09-07Epub Date: 2024-08-30DOI: 10.1016/S0140-6736(24)01763-X
Camilla Hage
{"title":"GLP-1 receptor agonists in heart failure: how far to expand use?","authors":"Camilla Hage","doi":"10.1016/S0140-6736(24)01763-X","DOIUrl":"10.1016/S0140-6736(24)01763-X","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LancetPub Date : 2024-09-07Epub Date: 2024-08-31DOI: 10.1016/S0140-6736(24)01678-7
Giulio G Stefanini, Angelo Oliva
{"title":"Is this the conclusive evidence for ticagrelor monotherapy in acute coronary syndromes?","authors":"Giulio G Stefanini, Angelo Oliva","doi":"10.1016/S0140-6736(24)01678-7","DOIUrl":"10.1016/S0140-6736(24)01678-7","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Congenital syphilis in a 2-month-old infant during Japanese outbreak.","authors":"Tomoaki Hirate, Kaori Kanda, Yumi Ohshima, Kunihiro Shinoda, Nobuyuki Tetsuka","doi":"10.1016/S0140-6736(24)01685-4","DOIUrl":"10.1016/S0140-6736(24)01685-4","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LancetPub Date : 2024-09-07Epub Date: 2024-08-29DOI: 10.1016/S0140-6736(24)01680-5
Dongju Shin, Dong-Jin Shin
{"title":"6 months on: South Korean medical students still on leave.","authors":"Dongju Shin, Dong-Jin Shin","doi":"10.1016/S0140-6736(24)01680-5","DOIUrl":"10.1016/S0140-6736(24)01680-5","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"Lancet","volume":null,"pages":null},"PeriodicalIF":98.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}