Age affects drug survival rates of interleukin (IL)‐17 and IL‐23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi‐country, cohort study
Background Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. Objectives To evaluate the drug survival of interleukin (IL)‐23 or the IL‐17 inhibitors approved for the treatment of moderate‐to‐severe psoriasis in elderly patients (aged ≥65 y...
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| creator | Chiricozzi, Andrea Coscarella, Giulia Puig, Luis Vender, Ron Yeung, Jensen Carrascosa, José‐Manuel Piaserico, Stefano Gisondi, Paolo Lynde, Charles Ferreira, Paulo Bastos, Pedro Mendes Dauden, Esteban Leite, Luiz Valerio, Joana Alcázar‐Viladomiu, Elena Vilarrasa, Eva Llamas‐Velasco, Mar Alessandri‐Bonetti, Mario Messina, Francesco Bruni, Manfredo Di Brizzi, Eugenia Veronica Ricceri, Federica Nidegger, Alessia Hugo, Jan Mufti, Asfandyar Daponte, Athina‐Ioanna Teixeira, Laetitia Balato, Anna Romanelli, Marco Prignano, Francesca Gkalpakiotis, Spyridon Conrad, Curdin Lazaridou, Elizabeth Rompoti, Natalia Stratigos, Alexander J. Nogueira, Miguel Peris, Ketty Torres, Tiago |
| description | Background
Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available.
Objectives
To evaluate the drug survival of interleukin (IL)‐23 or the IL‐17 inhibitors approved for the treatment of moderate‐to‐severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged |
| doi_str_mv | 10.1111/jdv.20143 |
| format | Article |
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Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available.
Objectives
To evaluate the drug survival of interleukin (IL)‐23 or the IL‐17 inhibitors approved for the treatment of moderate‐to‐severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival.
Methods
This retrospective multicentric cohort study included adult patients with moderate‐to‐severe psoriasis, dissecting two‐patient subcohorts based on age: elderly versus younger adults. Kaplan–Meier estimator and proportional hazard Cox regression models were used for drug survival analysis.
Results
We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log‐rank p < 0.006). This difference was significant for treatment courses involving IL‐23 inhibitors (p < 0.001) but not for those with IL‐17 inhibitors (p = 0.2). According to both uni‐ and multi‐variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062–1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010–1.422; p = 0.0377). Anti‐IL‐23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368–0.735; p < 0.001). Being previously treated with IL‐17 inhibitors increased the probability of discontinuation.
Conclusions
Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL‐23 inhibitors. However, in stratified analyses conducted in elderly patients, IL‐23 inhibitors showed higher drug survival rates than IL‐17 inhibitors.]]></description><identifier>ISSN: 0926-9959</identifier><identifier>ISSN: 1468-3083</identifier><identifier>EISSN: 1468-3083</identifier><identifier>DOI: 10.1111/jdv.20143</identifier><identifier>PMID: 38860729</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Age Factors ; Aged ; Antibodies, Monoclonal, Humanized - therapeutic use ; Dermatologic Agents - therapeutic use ; Female ; Humans ; Interleukin-17 - antagonists & inhibitors ; Interleukin-23 - antagonists & inhibitors ; Male ; Middle Aged ; Psoriasis - drug therapy ; Retrospective Studies</subject><ispartof>Journal of the European Academy of Dermatology and Venereology, 2024-11, Vol.38 (11), p.2175-2185</ispartof><rights>2024 European Academy of Dermatology and Venereology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2853-140fac9334c9bbdcd8584a789825ab9d9adcd3798f85ee0fe84b4357a3bbbfb63</cites><orcidid>0000-0002-2624-2724 ; 0000-0002-2547-3440 ; 0000-0003-0404-0870 ; 0000-0002-6956-5961 ; 0000-0002-0278-2443 ; 0000-0002-5997-2045 ; 0000-0002-1187-1341 ; 0000-0002-2439-920X ; 0000-0002-1777-9001 ; 0000-0003-4266-0771 ; 0000-0001-6083-0952 ; 0000-0002-7959-5881 ; 0000-0002-5935-356X ; 0000-0003-1883-4268 ; 0000-0001-7420-408X ; 0000-0003-1957-6600 ; 0000-0002-6739-0387 ; 0000-0002-0676-1260 ; 0000-0002-9326-6726 ; 0000-0002-4341-3812</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjdv.20143$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjdv.20143$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38860729$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chiricozzi, Andrea</creatorcontrib><creatorcontrib>Coscarella, Giulia</creatorcontrib><creatorcontrib>Puig, Luis</creatorcontrib><creatorcontrib>Vender, Ron</creatorcontrib><creatorcontrib>Yeung, Jensen</creatorcontrib><creatorcontrib>Carrascosa, José‐Manuel</creatorcontrib><creatorcontrib>Piaserico, Stefano</creatorcontrib><creatorcontrib>Gisondi, Paolo</creatorcontrib><creatorcontrib>Lynde, Charles</creatorcontrib><creatorcontrib>Ferreira, Paulo</creatorcontrib><creatorcontrib>Bastos, Pedro Mendes</creatorcontrib><creatorcontrib>Dauden, Esteban</creatorcontrib><creatorcontrib>Leite, Luiz</creatorcontrib><creatorcontrib>Valerio, Joana</creatorcontrib><creatorcontrib>Alcázar‐Viladomiu, Elena</creatorcontrib><creatorcontrib>Vilarrasa, Eva</creatorcontrib><creatorcontrib>Llamas‐Velasco, Mar</creatorcontrib><creatorcontrib>Alessandri‐Bonetti, Mario</creatorcontrib><creatorcontrib>Messina, Francesco</creatorcontrib><creatorcontrib>Bruni, Manfredo</creatorcontrib><creatorcontrib>Di Brizzi, Eugenia Veronica</creatorcontrib><creatorcontrib>Ricceri, Federica</creatorcontrib><creatorcontrib>Nidegger, Alessia</creatorcontrib><creatorcontrib>Hugo, Jan</creatorcontrib><creatorcontrib>Mufti, Asfandyar</creatorcontrib><creatorcontrib>Daponte, Athina‐Ioanna</creatorcontrib><creatorcontrib>Teixeira, Laetitia</creatorcontrib><creatorcontrib>Balato, Anna</creatorcontrib><creatorcontrib>Romanelli, Marco</creatorcontrib><creatorcontrib>Prignano, Francesca</creatorcontrib><creatorcontrib>Gkalpakiotis, Spyridon</creatorcontrib><creatorcontrib>Conrad, Curdin</creatorcontrib><creatorcontrib>Lazaridou, Elizabeth</creatorcontrib><creatorcontrib>Rompoti, Natalia</creatorcontrib><creatorcontrib>Stratigos, Alexander J.</creatorcontrib><creatorcontrib>Nogueira, Miguel</creatorcontrib><creatorcontrib>Peris, Ketty</creatorcontrib><creatorcontrib>Torres, Tiago</creatorcontrib><title>Age affects drug survival rates of interleukin (IL)‐17 and IL‐23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi‐country, cohort study</title><title>Journal of the European Academy of Dermatology and Venereology</title><addtitle>J Eur Acad Dermatol Venereol</addtitle><description><![CDATA[Background
Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available.
Objectives
To evaluate the drug survival of interleukin (IL)‐23 or the IL‐17 inhibitors approved for the treatment of moderate‐to‐severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival.
Methods
This retrospective multicentric cohort study included adult patients with moderate‐to‐severe psoriasis, dissecting two‐patient subcohorts based on age: elderly versus younger adults. Kaplan–Meier estimator and proportional hazard Cox regression models were used for drug survival analysis.
Results
We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log‐rank p < 0.006). This difference was significant for treatment courses involving IL‐23 inhibitors (p < 0.001) but not for those with IL‐17 inhibitors (p = 0.2). According to both uni‐ and multi‐variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062–1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010–1.422; p = 0.0377). Anti‐IL‐23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368–0.735; p < 0.001). Being previously treated with IL‐17 inhibitors increased the probability of discontinuation.
Conclusions
Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL‐23 inhibitors. However, in stratified analyses conducted in elderly patients, IL‐23 inhibitors showed higher drug survival rates than IL‐17 inhibitors.]]></description><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Dermatologic Agents - therapeutic use</subject><subject>Female</subject><subject>Humans</subject><subject>Interleukin-17 - antagonists & inhibitors</subject><subject>Interleukin-23 - antagonists & inhibitors</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Psoriasis - drug therapy</subject><subject>Retrospective 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affects drug survival rates of interleukin (IL)‐17 and IL‐23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi‐country, cohort study</title><author>Chiricozzi, Andrea ; Coscarella, Giulia ; Puig, Luis ; Vender, Ron ; Yeung, Jensen ; Carrascosa, José‐Manuel ; Piaserico, Stefano ; Gisondi, Paolo ; Lynde, Charles ; Ferreira, Paulo ; Bastos, Pedro Mendes ; Dauden, Esteban ; Leite, Luiz ; Valerio, Joana ; Alcázar‐Viladomiu, Elena ; Vilarrasa, Eva ; Llamas‐Velasco, Mar ; Alessandri‐Bonetti, Mario ; Messina, Francesco ; Bruni, Manfredo ; Di Brizzi, Eugenia Veronica ; Ricceri, Federica ; Nidegger, Alessia ; Hugo, Jan ; Mufti, Asfandyar ; Daponte, Athina‐Ioanna ; Teixeira, Laetitia ; Balato, Anna ; Romanelli, Marco ; Prignano, Francesca ; Gkalpakiotis, Spyridon ; Conrad, Curdin ; Lazaridou, Elizabeth ; Rompoti, Natalia ; Stratigos, Alexander J. ; Nogueira, Miguel ; Peris, Ketty ; Torres, Tiago</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2853-140fac9334c9bbdcd8584a789825ab9d9adcd3798f85ee0fe84b4357a3bbbfb63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Dermatologic Agents - therapeutic use</topic><topic>Female</topic><topic>Humans</topic><topic>Interleukin-17 - antagonists & inhibitors</topic><topic>Interleukin-23 - antagonists & inhibitors</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Psoriasis - drug therapy</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiricozzi, Andrea</creatorcontrib><creatorcontrib>Coscarella, Giulia</creatorcontrib><creatorcontrib>Puig, Luis</creatorcontrib><creatorcontrib>Vender, Ron</creatorcontrib><creatorcontrib>Yeung, Jensen</creatorcontrib><creatorcontrib>Carrascosa, José‐Manuel</creatorcontrib><creatorcontrib>Piaserico, Stefano</creatorcontrib><creatorcontrib>Gisondi, Paolo</creatorcontrib><creatorcontrib>Lynde, Charles</creatorcontrib><creatorcontrib>Ferreira, Paulo</creatorcontrib><creatorcontrib>Bastos, Pedro Mendes</creatorcontrib><creatorcontrib>Dauden, Esteban</creatorcontrib><creatorcontrib>Leite, Luiz</creatorcontrib><creatorcontrib>Valerio, Joana</creatorcontrib><creatorcontrib>Alcázar‐Viladomiu, Elena</creatorcontrib><creatorcontrib>Vilarrasa, Eva</creatorcontrib><creatorcontrib>Llamas‐Velasco, Mar</creatorcontrib><creatorcontrib>Alessandri‐Bonetti, Mario</creatorcontrib><creatorcontrib>Messina, Francesco</creatorcontrib><creatorcontrib>Bruni, Manfredo</creatorcontrib><creatorcontrib>Di Brizzi, Eugenia Veronica</creatorcontrib><creatorcontrib>Ricceri, Federica</creatorcontrib><creatorcontrib>Nidegger, Alessia</creatorcontrib><creatorcontrib>Hugo, Jan</creatorcontrib><creatorcontrib>Mufti, Asfandyar</creatorcontrib><creatorcontrib>Daponte, Athina‐Ioanna</creatorcontrib><creatorcontrib>Teixeira, Laetitia</creatorcontrib><creatorcontrib>Balato, Anna</creatorcontrib><creatorcontrib>Romanelli, Marco</creatorcontrib><creatorcontrib>Prignano, Francesca</creatorcontrib><creatorcontrib>Gkalpakiotis, Spyridon</creatorcontrib><creatorcontrib>Conrad, Curdin</creatorcontrib><creatorcontrib>Lazaridou, Elizabeth</creatorcontrib><creatorcontrib>Rompoti, Natalia</creatorcontrib><creatorcontrib>Stratigos, Alexander J.</creatorcontrib><creatorcontrib>Nogueira, Miguel</creatorcontrib><creatorcontrib>Peris, Ketty</creatorcontrib><creatorcontrib>Torres, Tiago</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the European Academy of Dermatology and Venereology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chiricozzi, Andrea</au><au>Coscarella, Giulia</au><au>Puig, Luis</au><au>Vender, Ron</au><au>Yeung, Jensen</au><au>Carrascosa, José‐Manuel</au><au>Piaserico, Stefano</au><au>Gisondi, Paolo</au><au>Lynde, Charles</au><au>Ferreira, Paulo</au><au>Bastos, Pedro Mendes</au><au>Dauden, Esteban</au><au>Leite, Luiz</au><au>Valerio, Joana</au><au>Alcázar‐Viladomiu, Elena</au><au>Vilarrasa, Eva</au><au>Llamas‐Velasco, Mar</au><au>Alessandri‐Bonetti, Mario</au><au>Messina, Francesco</au><au>Bruni, Manfredo</au><au>Di Brizzi, Eugenia Veronica</au><au>Ricceri, Federica</au><au>Nidegger, Alessia</au><au>Hugo, Jan</au><au>Mufti, Asfandyar</au><au>Daponte, Athina‐Ioanna</au><au>Teixeira, Laetitia</au><au>Balato, Anna</au><au>Romanelli, Marco</au><au>Prignano, Francesca</au><au>Gkalpakiotis, Spyridon</au><au>Conrad, Curdin</au><au>Lazaridou, Elizabeth</au><au>Rompoti, Natalia</au><au>Stratigos, Alexander J.</au><au>Nogueira, Miguel</au><au>Peris, Ketty</au><au>Torres, Tiago</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age affects drug survival rates of interleukin (IL)‐17 and IL‐23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi‐country, cohort study</atitle><jtitle>Journal of the European Academy of Dermatology and Venereology</jtitle><addtitle>J Eur Acad Dermatol Venereol</addtitle><date>2024-11</date><risdate>2024</risdate><volume>38</volume><issue>11</issue><spage>2175</spage><epage>2185</epage><pages>2175-2185</pages><issn>0926-9959</issn><issn>1468-3083</issn><eissn>1468-3083</eissn><abstract><![CDATA[Background
Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available.
Objectives
To evaluate the drug survival of interleukin (IL)‐23 or the IL‐17 inhibitors approved for the treatment of moderate‐to‐severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival.
Methods
This retrospective multicentric cohort study included adult patients with moderate‐to‐severe psoriasis, dissecting two‐patient subcohorts based on age: elderly versus younger adults. Kaplan–Meier estimator and proportional hazard Cox regression models were used for drug survival analysis.
Results
We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log‐rank p < 0.006). This difference was significant for treatment courses involving IL‐23 inhibitors (p < 0.001) but not for those with IL‐17 inhibitors (p = 0.2). According to both uni‐ and multi‐variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062–1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010–1.422; p = 0.0377). Anti‐IL‐23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368–0.735; p < 0.001). Being previously treated with IL‐17 inhibitors increased the probability of discontinuation.
Conclusions
Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL‐23 inhibitors. However, in stratified analyses conducted in elderly patients, IL‐23 inhibitors showed higher drug survival rates than IL‐17 inhibitors.]]></abstract><cop>England</cop><pmid>38860729</pmid><doi>10.1111/jdv.20143</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2624-2724</orcidid><orcidid>https://orcid.org/0000-0002-2547-3440</orcidid><orcidid>https://orcid.org/0000-0003-0404-0870</orcidid><orcidid>https://orcid.org/0000-0002-6956-5961</orcidid><orcidid>https://orcid.org/0000-0002-0278-2443</orcidid><orcidid>https://orcid.org/0000-0002-5997-2045</orcidid><orcidid>https://orcid.org/0000-0002-1187-1341</orcidid><orcidid>https://orcid.org/0000-0002-2439-920X</orcidid><orcidid>https://orcid.org/0000-0002-1777-9001</orcidid><orcidid>https://orcid.org/0000-0003-4266-0771</orcidid><orcidid>https://orcid.org/0000-0001-6083-0952</orcidid><orcidid>https://orcid.org/0000-0002-7959-5881</orcidid><orcidid>https://orcid.org/0000-0002-5935-356X</orcidid><orcidid>https://orcid.org/0000-0003-1883-4268</orcidid><orcidid>https://orcid.org/0000-0001-7420-408X</orcidid><orcidid>https://orcid.org/0000-0003-1957-6600</orcidid><orcidid>https://orcid.org/0000-0002-6739-0387</orcidid><orcidid>https://orcid.org/0000-0002-0676-1260</orcidid><orcidid>https://orcid.org/0000-0002-9326-6726</orcidid><orcidid>https://orcid.org/0000-0002-4341-3812</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0926-9959 |
| ispartof | Journal of the European Academy of Dermatology and Venereology, 2024-11, Vol.38 (11), p.2175-2185 |
| issn | 0926-9959 1468-3083 1468-3083 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3066790329 |
| source | Wiley-Blackwell Journals; MEDLINE |
| subjects | Adult Age Factors Aged Antibodies, Monoclonal, Humanized - therapeutic use Dermatologic Agents - therapeutic use Female Humans Interleukin-17 - antagonists & inhibitors Interleukin-23 - antagonists & inhibitors Male Middle Aged Psoriasis - drug therapy Retrospective Studies |
| title | Age affects drug survival rates of interleukin (IL)‐17 and IL‐23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi‐country, cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T08%3A54%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Age%20affects%20drug%20survival%20rates%20of%20interleukin%20(IL)%E2%80%9017%20and%20IL%E2%80%9023%20inhibitors%20in%20patients%20with%20plaque%20psoriasis:%20Results%20from%20a%20retrospective,%20multicentric,%20multi%E2%80%90country,%20cohort%20study&rft.jtitle=Journal%20of%20the%20European%20Academy%20of%20Dermatology%20and%20Venereology&rft.au=Chiricozzi,%20Andrea&rft.date=2024-11&rft.volume=38&rft.issue=11&rft.spage=2175&rft.epage=2185&rft.pages=2175-2185&rft.issn=0926-9959&rft.eissn=1468-3083&rft_id=info:doi/10.1111/jdv.20143&rft_dat=%3Cproquest_cross%3E3066790329%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3066790329&rft_id=info:pmid/38860729&rfr_iscdi=true |