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Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)-Catalyzed Enantioselective C(sp3)-H Functionalization. 揭示手性帕拉代二环在 Pd(II)-Catalyzed Enantioselective C(sp3)-H Functionalization 中的机理作用。
IF 16.1 1区 化学
Angewandte Chemie International Edition Pub Date : 2024-07-15 Epub Date: 2024-06-14 DOI: 10.1002/anie.202405062
Chen-Hui Yuan, Xiao-Xia Wang, Keyun Huang, Lei Jiao
{"title":"Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)-Catalyzed Enantioselective C(sp<sup>3</sup>)-H Functionalization.","authors":"Chen-Hui Yuan, Xiao-Xia Wang, Keyun Huang, Lei Jiao","doi":"10.1002/anie.202405062","DOIUrl":"10.1002/anie.202405062","url":null,"abstract":"<p><p>Palladium-catalyzed enantioselective C(sp<sup>3</sup>)-H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide-2-hydroxypridine (SOHP) catalytic system for asymmetric C(sp<sup>3</sup>)-H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)-catalyzed enantioselective C(sp<sup>3</sup>)-H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective β-C(sp<sup>3</sup>)-H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand-induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C-H functionalization. Our investigation provided direct evidence for the C-H palladation step as the enantioselectivity-determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)-catalyzed asymmetric C(sp<sup>3</sup>)-H functionalization reactions.</p>","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The right educational environment: Oral tolerance in early life. 正确的教育环境生命早期的口腔宽容
IF 7.5 2区 医学
Immunological Reviews Pub Date : 2024-07-13 DOI: 10.1111/imr.13366
Talia R Cheifetz, Kathryn A Knoop
{"title":"The right educational environment: Oral tolerance in early life.","authors":"Talia R Cheifetz, Kathryn A Knoop","doi":"10.1111/imr.13366","DOIUrl":"https://doi.org/10.1111/imr.13366","url":null,"abstract":"<p><p>Oral tolerance promotes the suppression of immune responses to innocuous antigen and is primarily mediated by regulatory T cell (Tregs). The development of oral tolerance begins in early life during a \"window of tolerance,\" which occurs around weaning and is mediated by components in breastmilk. Herein, we review the factors dictating this window and how Tregs are uniquely educated in early life. In early life, the translocation of luminal antigen for Treg induction is primarily dictated by goblet cell-associated antigen passages (GAPs). GAPs in the colon are negatively regulated by maternally-derived epidermal growth factor and the microbiota, restricting GAP formation to the \"periweaning\" period (postnatal day 11-21 in mice, 4-6 months in humans). The induction of solid food also promotes the diversification of the bacteria such that bacterially-derived metabolites known to promote Tregs-short-chain fatty acids, tryptophan metabolites, and bile acids-peak during the periweaning phase. Further, breastmilk immunoglobulins-IgA and IgG-regulate both microbial diversity and the interaction of microbes with the epithelium, further controlling which antigens are presented to T cells. Overall, these elements work in conjunction to induce a long-lived population of Tregs, around weaning, that are crucial for maintaining homeostasis in adults.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unlocking Spatial Surface Energy in Porous Skeletons: A Pathway to Bridging Electronic Circuits from 2D to 3D Architectures. 释放多孔骨架中的空间表面能:从二维到三维架构连接电子电路的途径。
IF 16.1 1区 化学
Angewandte Chemie International Edition Pub Date : 2024-07-13 DOI: 10.1002/anie.202412146
Shengwei Feng, Yuanyi Zhao, Xinjian Xie, Yingxue Sun, Xiongwei Luo, Wenqian Feng
{"title":"Unlocking Spatial Surface Energy in Porous Skeletons: A Pathway to Bridging Electronic Circuits from 2D to 3D Architectures.","authors":"Shengwei Feng, Yuanyi Zhao, Xinjian Xie, Yingxue Sun, Xiongwei Luo, Wenqian Feng","doi":"10.1002/anie.202412146","DOIUrl":"https://doi.org/10.1002/anie.202412146","url":null,"abstract":"<p><p>Conventional approaches to creating high-resolution electric circuits face challenges such as the requirement for skilled personnel and expensive equipment. In response, we propose an innovative strategy that leverages a photochemically modified porous polymer skeleton for in-situ circuit fabrication. By developing maskless surface energy manipulation that guides PEDOT:PSS-based conductive ink deposition, electric circuits with high precision, density, stability and adaptability are effortlessly engineered within or atop the porous skeleton, enabling transitions between 2D and 3D circuit configurations. This process simplifies prototyping while significantly reducing costs and maintaining efficiency, promising advancements across various technological sectors.</p>","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumour-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism. 肿瘤诱导的萎缩肌肉单核转录组变化表明蛋白质降解增强,氧化代谢降低。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle Pub Date : 2024-07-13 DOI: 10.1002/jcsm.13540
Samet Agca, Aylin Domaniku-Waraich, Sevval Nur Bilgic, Melis Sucuoglu, Meric Dag, Sukru Anil Dogan, Serkan Kir
{"title":"Tumour-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism.","authors":"Samet Agca, Aylin Domaniku-Waraich, Sevval Nur Bilgic, Melis Sucuoglu, Meric Dag, Sukru Anil Dogan, Serkan Kir","doi":"10.1002/jcsm.13540","DOIUrl":"https://doi.org/10.1002/jcsm.13540","url":null,"abstract":"<p><strong>Background: </strong>Tumour-induced skeletal muscle wasting in the context of cancer cachexia is a condition with profound implications for patient survival. The loss of muscle mass is a significant clinical obstacle and is linked to reduced tolerance to chemotherapy and increased frailty. Understanding the molecular mechanisms driving muscle atrophy is crucial for the design of new therapeutics.</p><p><strong>Methods: </strong>Lewis lung carcinoma tumours were utilized to induce cachexia and muscle atrophy in mice. Single-nucleus libraries of the tibialis anterior (TA) muscle from tumour-bearing mice and their non-tumour-bearing controls were constructed using 10X Genomics applications following the manufacturer's guidelines. RNA sequencing results were analysed with Cell Ranger software and the Seurat R package. Oxygen consumption of mitochondria isolated from TA muscle was measured using an Oroboros O2k-FluoRespirometer. Mouse primary myotubes were treated with a recombinant ectodysplasin A2 (EDA-A2) protein to activate EDA-A2 receptor (EDA2R) signalling and study changes in gene expression and oxygen consumption.</p><p><strong>Results: </strong>Tumour-bearing mice were sacrificed while exhibiting moderate cachexia. Average TA muscle weight was reduced by 11% (P = 0.0207) in these mice. A total of 12 335 nuclei, comprising 6422 nuclei from the control group and 5892 nuclei from atrophying muscles, were studied. The analysis of single-nucleus transcriptomes identified distinct myonuclear gene signatures and a shift towards type IIb myonuclei. Muscle atrophy-related genes, including Atrogin1, MuRF1 and Eda2r, were upregulated in these myonuclei, emphasizing their crucial roles in muscle wasting. Gene set enrichment analysis demonstrated that EDA2R activation and tumour inoculation led to similar expression patterns in muscle cells, including the stimulation of nuclear factor-kappa B, Janus kinase-signal transducer and activator of transcription and transforming growth factor-beta pathways and the suppression of myogenesis and oxidative phosphorylation. Muscle oxidative metabolism was suppressed by both tumours and EDA2R activation.</p><p><strong>Conclusions: </strong>This study identified tumour-induced transcriptional changes in muscle tissue at single-nucleus resolution and highlighted the negative impact of tumours on oxidative metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying muscle wasting.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597978","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}
引用次数: 0
Mid-Infrared Photoacoustic Stimulation of Neurons through Vibrational Excitation in Polydimethylsiloxane. 通过聚二甲基硅氧烷中的振动激发对神经元的中红外光声刺激。
IF 14.3 1区 材料科学
Advanced Science Pub Date : 2024-07-12 DOI: 10.1002/advs.202405677
Zhiyi Du, Mingsheng Li, Guo Chen, Maijie Xiang, Danchen Jia, Ji-Xin Cheng, Chen Yang
{"title":"Mid-Infrared Photoacoustic Stimulation of Neurons through Vibrational Excitation in Polydimethylsiloxane.","authors":"Zhiyi Du, Mingsheng Li, Guo Chen, Maijie Xiang, Danchen Jia, Ji-Xin Cheng, Chen Yang","doi":"10.1002/advs.202405677","DOIUrl":"https://doi.org/10.1002/advs.202405677","url":null,"abstract":"<p><p>Photoacoustic (PA) emitters are emerging ultrasound sources offering high spatial resolution and ease of miniaturization. Thus far, PA emitters rely on electronic transitions of absorbers embedded in an expansion matrix such as polydimethylsiloxane (PDMS). Here, it is shown that mid-infrared vibrational excitation of C─H bonds in a transparent PDMS film can lead to efficient mid-infrared photoacoustic conversion (MIPA). MIPA shows 37.5 times more efficient than the commonly used PA emitters based on carbon nanotubes embedded in PDMS. Successful neural stimulation through MIPA both in a wide field with a size up to a 100 µm radius and in single-cell precision is achieved. Owing to the low heat conductivity of PDMS, less than a 0.5 °C temperature increase is found on the surface of a PDMS film during successful neural stimulation, suggesting a non-thermal mechanism. MIPA emitters allow repetitive wide-field neural stimulation, opening up opportunities for high-throughput screening of mechano-sensitive ion channels and regulators.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Letter: Risks of proton pump inhibitor treatment in cirrhotic patients-Authors' reply. 信:肝硬化患者接受质子泵抑制剂治疗的风险--作者的回复。
IF 6.6 1区 医学
Alimentary Pharmacology & Therapeutics Pub Date : 2024-07-12 DOI: 10.1111/apt.18167
Jun Sik Yoon, Jeong-Hoon Lee
{"title":"Letter: Risks of proton pump inhibitor treatment in cirrhotic patients-Authors' reply.","authors":"Jun Sik Yoon, Jeong-Hoon Lee","doi":"10.1111/apt.18167","DOIUrl":"https://doi.org/10.1111/apt.18167","url":null,"abstract":"","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597960","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}
引用次数: 0
High physical activity is associated with greater cortical bone size, better physical function, and with lower risk of incident fractures independently of clinical risk factors in older women from the SUPERB study. 在 SUPERB 研究的老年妇女中,大量体育锻炼与更大的皮质骨大小、更好的身体功能以及更低的骨折风险相关,而与临床风险因素无关。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2024-07-12 DOI: 10.1093/jbmr/zjae114
Lisa Johansson, Henrik Litsne, Kristian Axelsson, Mattias Lorentzon
{"title":"High physical activity is associated with greater cortical bone size, better physical function, and with lower risk of incident fractures independently of clinical risk factors in older women from the SUPERB study.","authors":"Lisa Johansson, Henrik Litsne, Kristian Axelsson, Mattias Lorentzon","doi":"10.1093/jbmr/zjae114","DOIUrl":"https://doi.org/10.1093/jbmr/zjae114","url":null,"abstract":"<p><p>The Physical Activity Scale for the Elderly (PASE) is a validated test to assess physical activity in older people. It has not been investigated if physical activity, according to PASE, is associated with fracture risk independently from the clinical risk factors (CRFs) in FRAX, bone mineral density (BMD), comorbidity, and if such an association is due to differences in physical performance or bone parameters. The purpose of this study was to evaluate if PASE score is associated with bone characteristics, physical function, and independently predicts incident fracture in 3014 75-80-year-old women from the population-based cross-sectional SUPERB study. At baseline participants answered questionnaires, and underwent physical function tests, detailed bone phenotyping with dual x-ray absorptiometry, and high-resolution peripheral quantitative computed tomography. Incident fractures were x-ray verified. Cox regression models were used to assess the association between PASE score and incident fractures, with adjustments for CRFs, FN BMD and Charlson comorbidity index. Women were divided into quartiles according to PASE score. Quartile differences in bone parameters (1.56% for cortical volumetric BMD and 4.08% for cortical area, Q4 vs. Q1, p = 0.007 and p = 0.022, respectively) were smaller than quartile differences in physical performance (27% shorter timed up and go test, 52% longer one leg standing time, Q4 vs. Q1). During 8 years (median, range 0.20-9.9) of follow-up, 1077 women had any fracture, 806 a major osteoporotic fracture (MOF; spine, hip, forearm, humerus), and 236 a hip fracture. Women in Q4 had 30% lower risk of any fracture, 32% lower risk of MOF, and 54% lower risk of hip fracture, compared to women in Q1. These associations remained in fully adjusted models. In conclusion, high physical activity was associated with substantially better physical function and a lower risk of any fracture, MOF and hip fracture, independently of risk factors used in FRAX, FN BMD and comorbidity.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597973","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}
引用次数: 0
Controlling Triboelectric Charge of MOFs by Leveraging Ligands Chemistry. 利用配体化学控制 MOFs 的三电荷。
IF 14.3 1区 材料科学
Advanced Science Pub Date : 2024-07-12 DOI: 10.1002/advs.202404993
Muhammad Noman, Qazi Muhammad Saqib, Shahid Ameen, Swapnil R Patil, Chandrashekhar S Patil, Jungmin Kim, Youngbin Ko, BongSoo Kim, Jinho Bae
{"title":"Controlling Triboelectric Charge of MOFs by Leveraging Ligands Chemistry.","authors":"Muhammad Noman, Qazi Muhammad Saqib, Shahid Ameen, Swapnil R Patil, Chandrashekhar S Patil, Jungmin Kim, Youngbin Ko, BongSoo Kim, Jinho Bae","doi":"10.1002/advs.202404993","DOIUrl":"https://doi.org/10.1002/advs.202404993","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) have emerged as promising materials for triboelectric nanogenerators (TENGs), but the effects of ligand choice on triboelectric charge remain underexplored. Hence, this paper demonstrates the effect of single, binary, and ternary ligands on TENG performance of cobalt/cerium-based (Co─Ce) bimetallic MOFs utilizing 2-methylimidazole (2Melm), terephthalic acid (BDC), and benzene tricarboxylic acid (BTC) as ligands. The detailed structural characterization revealed that varying ligand chemistries led to distinct MOF features affecting TENG performance. Single ligand bimetallic MOFs (designated as CoCe-2MeIm, CoCe-BDC, CoCe-BTC) has lower performance than binary ligand (designated as CoCe-2MeIm-BDC, CoCe-2MeIm-BTC, CoCe-BDC-BTC) and ternary ligand MOFs (designated as CoCe-2MeIm-BDC-BTC). Among all, the binary ligand MOF, CoCe-2MeIm-BTC, shows the best results (598 V, 26.7 µA) due to the combined effect of imidazole ring and (─COO─) groups. This is attributed to lone pairs on nitrogen atoms and a delocalized π-electron system in imidazole system in this material. CoCe-BTC has the lowest results (31 V, 3.2 µA) due to the bulkier nature of the electron-withdrawing (─COO─) groups and their impact on the π-electron system of the benzene ring. This study showcases the potential of ligand chemistry manipulation to control triboelectric charge and thereby enhance MOF-based TENG performance.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Highly Selective Fluorescent Probe for Monitoring the Thyroid Hormone Transporter Activity in Mammalian Cells. 用于监测哺乳动物细胞中甲状腺激素转运体活性的高选择性荧光探针
IF 3.9 2区 化学
Chemistry - A European Journal Pub Date : 2024-07-12 DOI: 10.1002/chem.202401719
Debasish Giri, Vijayakumar Govindaraj, Sagar Kumar, Harinarayana Ungati, Govindasamy Mugesh
{"title":"A Highly Selective Fluorescent Probe for Monitoring the Thyroid Hormone Transporter Activity in Mammalian Cells.","authors":"Debasish Giri, Vijayakumar Govindaraj, Sagar Kumar, Harinarayana Ungati, Govindasamy Mugesh","doi":"10.1002/chem.202401719","DOIUrl":"https://doi.org/10.1002/chem.202401719","url":null,"abstract":"<p><p>Monocarboxylate transporter 8 (MCT8) is a trans-membrane transporter, which mediates the cellular delivery of thyroid hormones, L-thyroxine (T4) and 3,5,3 '-triiodo-L-thyronine (T3). In humans, the MCT8 protein is encoded by the SLC16A2 gene and mutations in the transporter cause a genetic neurological disorder known as Allan-Herndon-Dudley syndrome (AHDS). MCT8 deficiency leads to impaired transport of thyroid hormones in the brain. Radiolabelled T4 and T3 or LC/MS-MS methods have been used to monitor the thyroid hormone uptake through MCT8. Herein, we developed a fluorescent based assay to monitor the thyroid hormone uptake through MCT8. A dansyl-based fluorescent probe having L-thyroxine moiety is found to be highly selective towards MCT8 in living cells. The high selectivity of the probe towards MCT8 can be attributed to the halogen bond-mediated recognition by the transporter protein. The presence of a free carboxylic acid group is essential for the specificity of the probe towards MCT8. Additionally, the selectivity of the probe for MCT8 is abolished upon esterification of the carboxylic group. Similarly, MCT8 does not recognize the probe when it contains a free amine group.</p>","PeriodicalId":144,"journal":{"name":"Chemistry - A European Journal","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A target trial emulation comparing the antidepressant effectiveness of selective serotonin reuptake inhibitors (SSRIs) highlighting the importance of patent-related confounding by indication. 比较选择性 5-羟色胺再摄取抑制剂(SSRIs)的抗抑郁效果的目标试验模拟,突出了与专利相关的适应症混杂的重要性。
IF 5.3 2区 医学
Acta Psychiatrica Scandinavica Pub Date : 2024-07-12 DOI: 10.1111/acps.13729
Christopher Rohde, Fredrik Hieronymus, Søren Dinesen Østergaard
{"title":"A target trial emulation comparing the antidepressant effectiveness of selective serotonin reuptake inhibitors (SSRIs) highlighting the importance of patent-related confounding by indication.","authors":"Christopher Rohde, Fredrik Hieronymus, Søren Dinesen Østergaard","doi":"10.1111/acps.13729","DOIUrl":"https://doi.org/10.1111/acps.13729","url":null,"abstract":"<p><strong>Background: </strong>The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram.</p><p><strong>Aims: </strong>To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice.</p><p><strong>Method: </strong>We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of (\"patent-related\") confounding by indication.</p><p><strong>Results: </strong>We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events.</p><p><strong>Conclusions: </strong>Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.</p>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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