Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0914
Geoffrey S Baird, Edwin G Lindo
{"title":"Reducing the Harm of Urine Drug Screening in Pregnancy.","authors":"Geoffrey S Baird, Edwin G Lindo","doi":"10.1001/jamanetworkopen.2025.0914","DOIUrl":"https://doi.org/10.1001/jamanetworkopen.2025.0914","url":null,"abstract":"","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250914"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648541","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}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0128
Daniel Jay Riskin, Keri L Monda, Joshua J Gagne, Robert Reynolds, A Reshad Garan, Nancy Dreyer, Paul Muntner, Brian D Bradbury
<p><strong>Importance: </strong>While it is well known that data quality underlies evidence validity, the measurement and impacts of data reliability are less well understood. The need has been highlighted in the 21st Century Cures Act of 2016 and US Food and Drug Administration (FDA) Real-World Evidence Program framework in 2018, draft guidance in 2021 and final guidance in 2024. Timely visibility into implementation may be provided by the Transforming Real-World Evidence With Unstructured and Structured Data to Advance Tailored Therapy (TRUST) study, a Verantos Inc-led FDA-funded demonstration project to explore data quality and inform regulatory decision-making.</p><p><strong>Objective: </strong>To report early learnings from the TRUST study on distilling data reliability to practice including developing a practical approach to quantify accuracy, completeness, and traceability of real-world data (routinely collected patient health data) and comparing traditional to advanced data and technologies on these dimensions.</p><p><strong>Design, setting, and participants: </strong>This quality improvement study was performed using data from 58 hospitals and more than 1180 associated outpatient clinics from academic and community settings in the US. Participants included patients with asthma treated between January 1, 2014, and December 31, 2022. Data were analyzed from January 1 to June 30, 2024.</p><p><strong>Exposures: </strong>The traditional approach used medical and pharmacy claims as source documentation. The advanced approach used medical and pharmacy claims, electronic health records with unstructured data extracted using artificial intelligence methods, and mortality registry data.</p><p><strong>Main outcomes and measures: </strong>Accuracy was assessed using the F1 score. Completeness was estimated as a weighted mean of available data sources during each calendar year under study for each patient. Traceability was estimated as the proportion of data elements identified in clinical source documentation.</p><p><strong>Results: </strong>In total, 120 616 patients met the minimum data requirements (mean [SD] age, 43.2 [18.5] years; 41 011 male [34.0%]). For accuracy, traditional approaches had F1 scores of 59.5% and advanced approaches had scores of 93.4%. For completeness, traditional approaches yielded mean scores of 46.1% (95% CI, 38.2%-54.0%); advanced approaches, 96.6% (95% CI, 85.8%-1.1%). For traceability, traditional approaches had 11.5% (95% CI, 11.4%-11.5%) and advanced approaches had 77.3% (95% CI, 77.3%-77.3%) of data elements traceable to clinical source data.</p><p><strong>Conclusions and relevance: </strong>In this study, practical implementation of data reliability measurement is described. Findings suggest the potential of using multiple data sources and applying advanced methods to increase real-world data reliability. The inclusion of data reliability standards when generating evidence from these sources has the potential to s
{"title":"Implementing Accuracy, Completeness, and Traceability for Data Reliability.","authors":"Daniel Jay Riskin, Keri L Monda, Joshua J Gagne, Robert Reynolds, A Reshad Garan, Nancy Dreyer, Paul Muntner, Brian D Bradbury","doi":"10.1001/jamanetworkopen.2025.0128","DOIUrl":"10.1001/jamanetworkopen.2025.0128","url":null,"abstract":"<p><strong>Importance: </strong>While it is well known that data quality underlies evidence validity, the measurement and impacts of data reliability are less well understood. The need has been highlighted in the 21st Century Cures Act of 2016 and US Food and Drug Administration (FDA) Real-World Evidence Program framework in 2018, draft guidance in 2021 and final guidance in 2024. Timely visibility into implementation may be provided by the Transforming Real-World Evidence With Unstructured and Structured Data to Advance Tailored Therapy (TRUST) study, a Verantos Inc-led FDA-funded demonstration project to explore data quality and inform regulatory decision-making.</p><p><strong>Objective: </strong>To report early learnings from the TRUST study on distilling data reliability to practice including developing a practical approach to quantify accuracy, completeness, and traceability of real-world data (routinely collected patient health data) and comparing traditional to advanced data and technologies on these dimensions.</p><p><strong>Design, setting, and participants: </strong>This quality improvement study was performed using data from 58 hospitals and more than 1180 associated outpatient clinics from academic and community settings in the US. Participants included patients with asthma treated between January 1, 2014, and December 31, 2022. Data were analyzed from January 1 to June 30, 2024.</p><p><strong>Exposures: </strong>The traditional approach used medical and pharmacy claims as source documentation. The advanced approach used medical and pharmacy claims, electronic health records with unstructured data extracted using artificial intelligence methods, and mortality registry data.</p><p><strong>Main outcomes and measures: </strong>Accuracy was assessed using the F1 score. Completeness was estimated as a weighted mean of available data sources during each calendar year under study for each patient. Traceability was estimated as the proportion of data elements identified in clinical source documentation.</p><p><strong>Results: </strong>In total, 120 616 patients met the minimum data requirements (mean [SD] age, 43.2 [18.5] years; 41 011 male [34.0%]). For accuracy, traditional approaches had F1 scores of 59.5% and advanced approaches had scores of 93.4%. For completeness, traditional approaches yielded mean scores of 46.1% (95% CI, 38.2%-54.0%); advanced approaches, 96.6% (95% CI, 85.8%-1.1%). For traceability, traditional approaches had 11.5% (95% CI, 11.4%-11.5%) and advanced approaches had 77.3% (95% CI, 77.3%-77.3%) of data elements traceable to clinical source data.</p><p><strong>Conclusions and relevance: </strong>In this study, practical implementation of data reliability measurement is described. Findings suggest the potential of using multiple data sources and applying advanced methods to increase real-world data reliability. The inclusion of data reliability standards when generating evidence from these sources has the potential to s","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250128"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0341
Lyndon P James, Natasha K Stout, Taliser R Avery, Sarah Stein, Kenneth E Sands, Edward J Septimus, Julia Moody, Eunice J Blanchard, Russell E Poland, Richard Platt, Susan S Huang
Importance: The ABATE Infection trial investigated the effects of universal bacterial decolonization with chlorhexidine for patients in non-intensive care unit settings to reduce hospital-onset bacteremia and fungemia (HOB) events. Among patients with medical devices (central venous catheters, midline catheters, and lumbar drains), universal decolonization (UD) resulted in a significant and meaningful reduction in bacteremia compared with the standard of care (SOC), but cost-effectiveness is unclear.
Objective: To examine the cost-effectiveness of universal and targeted bathing strategies compared with SOC in general medical and surgical units.
Design, setting, and participants: A decision analytic model was constructed from June 1, 2021, to May 31, 2024, to simulate the frequency of HOB and costs under 3 strategies: SOC, UD, and targeted decolonization (TD). The model included a simulated cohort representative of the cluster-randomized ABATE Infection trial, which involved more than 500 000 participants across the US.
Main outcomes and measures: In TD, decolonization was administered for patients with medical devices only. Upstream costs of bathing and downstream costs of HOB, under payer and hospital perspectives were included. Parameters were informed by the ABATE Infection Trial and additional literature. Willingness-to-pay per HOB prevented was adopted as $25 000 for payers and $10 000 for hospitals. Sensitivity analyses were tailored to populations with different characteristics.
Results: The simulated cohort, based on the population from the ABATE trial, included 529 000 adult admissions with a mean (SD) age of 63 (18) years, 54% female, and 13% with a central venous catheter, midline catheter, or lumbar drain. In the base case, the SOC was least effective and most costly. Targeted decolonization was least costly and UD resulted in the fewest HOB events. Targeted decolonization was the cost-effective strategy from payer and hospital perspectives. Compared with TD, UD had an incremental cost-effectiveness ratio of $119 700 per HOB averted from the payer perspective, and $126 600 per HOB averted from the hospital perspective. Depending on willingness-to-pay, UD may be preferred in scenarios with a higher proportion of patients with medical devices, greater reductions in HOB from decolonizing in those with devices, and lower adherence under TD.
Conclusions and relevance: In this decision analytic model studying universal and targeted bathing, TD was cost-effective under a broad range of scenarios for both hospital system and payer decision-makers. Universal decolonization was cost-effective in some scenarios, such as in specific units where many patients have medical devices or if it were difficult to implement a targeted approach.
{"title":"Universal vs Targeted Chlorhexidine Bathing and Nasal Decolonization in Hospitalized Patients.","authors":"Lyndon P James, Natasha K Stout, Taliser R Avery, Sarah Stein, Kenneth E Sands, Edward J Septimus, Julia Moody, Eunice J Blanchard, Russell E Poland, Richard Platt, Susan S Huang","doi":"10.1001/jamanetworkopen.2025.0341","DOIUrl":"10.1001/jamanetworkopen.2025.0341","url":null,"abstract":"<p><strong>Importance: </strong>The ABATE Infection trial investigated the effects of universal bacterial decolonization with chlorhexidine for patients in non-intensive care unit settings to reduce hospital-onset bacteremia and fungemia (HOB) events. Among patients with medical devices (central venous catheters, midline catheters, and lumbar drains), universal decolonization (UD) resulted in a significant and meaningful reduction in bacteremia compared with the standard of care (SOC), but cost-effectiveness is unclear.</p><p><strong>Objective: </strong>To examine the cost-effectiveness of universal and targeted bathing strategies compared with SOC in general medical and surgical units.</p><p><strong>Design, setting, and participants: </strong>A decision analytic model was constructed from June 1, 2021, to May 31, 2024, to simulate the frequency of HOB and costs under 3 strategies: SOC, UD, and targeted decolonization (TD). The model included a simulated cohort representative of the cluster-randomized ABATE Infection trial, which involved more than 500 000 participants across the US.</p><p><strong>Main outcomes and measures: </strong>In TD, decolonization was administered for patients with medical devices only. Upstream costs of bathing and downstream costs of HOB, under payer and hospital perspectives were included. Parameters were informed by the ABATE Infection Trial and additional literature. Willingness-to-pay per HOB prevented was adopted as $25 000 for payers and $10 000 for hospitals. Sensitivity analyses were tailored to populations with different characteristics.</p><p><strong>Results: </strong>The simulated cohort, based on the population from the ABATE trial, included 529 000 adult admissions with a mean (SD) age of 63 (18) years, 54% female, and 13% with a central venous catheter, midline catheter, or lumbar drain. In the base case, the SOC was least effective and most costly. Targeted decolonization was least costly and UD resulted in the fewest HOB events. Targeted decolonization was the cost-effective strategy from payer and hospital perspectives. Compared with TD, UD had an incremental cost-effectiveness ratio of $119 700 per HOB averted from the payer perspective, and $126 600 per HOB averted from the hospital perspective. Depending on willingness-to-pay, UD may be preferred in scenarios with a higher proportion of patients with medical devices, greater reductions in HOB from decolonizing in those with devices, and lower adherence under TD.</p><p><strong>Conclusions and relevance: </strong>In this decision analytic model studying universal and targeted bathing, TD was cost-effective under a broad range of scenarios for both hospital system and payer decision-makers. Universal decolonization was cost-effective in some scenarios, such as in specific units where many patients have medical devices or if it were difficult to implement a targeted approach.</p>","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250341"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0535
Quan Sun, Jiawen Du, Yihan Tang, Lyle G Best, Karin Haack, Ying Zhang, Shelley A Cole, Nora Franceschini
<p><strong>Importance: </strong>Numerous efforts have been made to include diverse populations in genetic studies, but American Indian populations are still severely underrepresented. Polygenic scores derived from genetic data have been proposed in clinical care, but how polygenic scores perform in American Indian individuals and whether they can predict disease risk in this population remains unknown.</p><p><strong>Objective: </strong>To study the performance of polygenic scores for cardiometabolic risk factors of lipid traits and C-reactive protein in American Indian adults and to determine whether such scores are helpful in clinical prediction for cardiometabolic diseases.</p><p><strong>Design, setting, and participants: </strong>The Strong Heart Study (SHS) is a large American Indian cohort recruited from 1989 to 1991, with ongoing follow-up (phase VII). In this genetic association study, data from SHS American Indian participants were used in addition to data from 2 large-scale, external, ancestry-mismatched genome-wide association studies (GWASs; 450 865 individuals from a European GWAS and 33 096 individuals from a multi-ancestry GWAS) and 1 small-scale internal ancestry-matched American Indian GWAS (2000 individuals). Analyses were conducted from February 2023 to August 2024.</p><p><strong>Exposure: </strong>Genetic risk score for cardiometabolic disease risk factors from 6 traits including 5 lipids (apolipoprotein A, apolipoprotein B, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), and an inflammatory biomarker (C-reactive protein [CRP]).</p><p><strong>Main outcomes and measures: </strong>Data from SHS participants and the 2 GWASs were used to construct 8 polygenic scores. The association of polygenic scores with cardiometabolic disease was assessed using 2-sided z tests and 1-sided likelihood ratio tests.</p><p><strong>Results: </strong>In the 3157 SHS participants (mean [SD] age, 56.44 [8.12] years; 1845 female [58.4%]), a large European-based polygenic score had the most robust performance (mean [SD] R2 = 5.0% [1.7%]), but adding a small-scale ancestry-matched GWAS using American Indian data helped improve polygenic score prediction for 5 of 6 traits (all but CRP; mean [SD] R2, 7.6% [3.2%]). Lipid polygenic scores developed in American Indian individuals improved prediction of diabetes compared with baseline clinical risk factors (area under the curve for absolute improvement, 0.86%; 95% CI, 0.78%-0.93%; likelihood ratio test P = 3.8 × 10-3).</p><p><strong>Conclusions and relevance: </strong>In this genetic association study of lipids and CRP among American Indian individuals, polygenic scores of lipid traits were found to improve prediction of diabetes when added to clinical risk factors, although the magnitude of improvement was small. The transferability of polygenic scores derived from other populations is still a concern, with implications for the advancement of precision medicine an
{"title":"Polygenic Scores of Cardiometabolic Risk Factors in American Indian Adults.","authors":"Quan Sun, Jiawen Du, Yihan Tang, Lyle G Best, Karin Haack, Ying Zhang, Shelley A Cole, Nora Franceschini","doi":"10.1001/jamanetworkopen.2025.0535","DOIUrl":"10.1001/jamanetworkopen.2025.0535","url":null,"abstract":"<p><strong>Importance: </strong>Numerous efforts have been made to include diverse populations in genetic studies, but American Indian populations are still severely underrepresented. Polygenic scores derived from genetic data have been proposed in clinical care, but how polygenic scores perform in American Indian individuals and whether they can predict disease risk in this population remains unknown.</p><p><strong>Objective: </strong>To study the performance of polygenic scores for cardiometabolic risk factors of lipid traits and C-reactive protein in American Indian adults and to determine whether such scores are helpful in clinical prediction for cardiometabolic diseases.</p><p><strong>Design, setting, and participants: </strong>The Strong Heart Study (SHS) is a large American Indian cohort recruited from 1989 to 1991, with ongoing follow-up (phase VII). In this genetic association study, data from SHS American Indian participants were used in addition to data from 2 large-scale, external, ancestry-mismatched genome-wide association studies (GWASs; 450 865 individuals from a European GWAS and 33 096 individuals from a multi-ancestry GWAS) and 1 small-scale internal ancestry-matched American Indian GWAS (2000 individuals). Analyses were conducted from February 2023 to August 2024.</p><p><strong>Exposure: </strong>Genetic risk score for cardiometabolic disease risk factors from 6 traits including 5 lipids (apolipoprotein A, apolipoprotein B, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), and an inflammatory biomarker (C-reactive protein [CRP]).</p><p><strong>Main outcomes and measures: </strong>Data from SHS participants and the 2 GWASs were used to construct 8 polygenic scores. The association of polygenic scores with cardiometabolic disease was assessed using 2-sided z tests and 1-sided likelihood ratio tests.</p><p><strong>Results: </strong>In the 3157 SHS participants (mean [SD] age, 56.44 [8.12] years; 1845 female [58.4%]), a large European-based polygenic score had the most robust performance (mean [SD] R2 = 5.0% [1.7%]), but adding a small-scale ancestry-matched GWAS using American Indian data helped improve polygenic score prediction for 5 of 6 traits (all but CRP; mean [SD] R2, 7.6% [3.2%]). Lipid polygenic scores developed in American Indian individuals improved prediction of diabetes compared with baseline clinical risk factors (area under the curve for absolute improvement, 0.86%; 95% CI, 0.78%-0.93%; likelihood ratio test P = 3.8 × 10-3).</p><p><strong>Conclusions and relevance: </strong>In this genetic association study of lipids and CRP among American Indian individuals, polygenic scores of lipid traits were found to improve prediction of diabetes when added to clinical risk factors, although the magnitude of improvement was small. The transferability of polygenic scores derived from other populations is still a concern, with implications for the advancement of precision medicine an","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250535"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0171
Daria E A Jensen, Klaus P Ebmeier, Tasnime Akbaraly, Michelle G Jansen, Archana Singh-Manoux, Mika Kivimäki, Eniko Zsoldos, Miriam C Klein-Flügge, Sana Suri
<p><strong>Importance: </strong>Epidemiological studies suggest that lifestyle factors are associated with risk of dementia. However, few studies have examined the association of diet and waist to hip ratio (WHR) with hippocampus connectivity and cognitive health.</p><p><strong>Objective: </strong>To ascertain how longitudinal changes in diet quality and WHR during midlife are associated with hippocampal connectivity and cognitive function in later life.</p><p><strong>Design, setting, and participants: </strong>This cohort study analyzed data from participants in the Whitehall II Study at University College London (study inception: 1985) and Whitehall II Imaging Substudy at the University of Oxford (data collection: 2012-2016). Healthy participants from the Whitehall II Imaging Study with a mean age of 48 years at baseline to 70 years at magnetic resonance imaging (MRI) were included if they had information on diet from at least 1 wave, information on WHR from at least 2 waves, and good-quality MRI scans. Study analyses were completed from October 2019 to November 2024.</p><p><strong>Exposures: </strong>Diet quality was measured in participants(mean age, 48 years at baseline to 60 years) using the Alternative Healthy Eating Index-2010 score, which was assessed 3 times across 11 years. WHR was measured 5 times over 21 years in participants aged 48 to 68 years.</p><p><strong>Main outcomes and measures: </strong>White matter structural connectivity assessed using diffusion tensor imaging, hippocampal functional connectivity assessed using resting-state functional MRI, and cognitive performance measures. Brain imaging and cognitive tests were performed at a mean (SD) age of 70 (5) years.</p><p><strong>Results: </strong>The final diet quality sample comprised 512 participants (403 males [78.7%]; mean [SD] age, 47.8 [5.2] years), and the final WHR sample included 664 participants (532 males [80.1%]; mean [SD] age, 47.7 [5.1] years). Better diet quality in midlife and from midlife to late life was associated with higher hippocampal functional connectivity to the occipital lobe and cerebellum (left hippocampus: 9176 mm3, P < .05; left hippocampus and to the right cerebellum: 136 mm3, P = .04) and better white matter integrity as measured by higher fractional anisotropy (FA; 19 432 mm3, P < .05) and lower diffusivity (mean diffusivity [MD]: 5560 mm3, P < .05; axial diffusivity [AD]: 2600 mm3, P < .045; AD in fornix: β [SE] = 0.26 [0.11], false discovery rate-corrected P = .02). Higher WHR in midlife was associated with higher MD and radial diffusivity (covering 26.4% [333 088 mm3, P < .001] and 23.1% [291 888 mm3, P < .05], respectively, of the total white matter tracts in the cingulum and superior and inferior longitudinal fasciculus) and lower FA in the corticospinal tract (covering 4.9% of the white matter skeleton), including the inferior longitudinal fasciculus and cingulum (61 272 mm3, P < .05). Associations between midlife WHR, working memory, and
{"title":"Association of Diet and Waist-to-Hip Ratio With Brain Connectivity and Memory in Aging.","authors":"Daria E A Jensen, Klaus P Ebmeier, Tasnime Akbaraly, Michelle G Jansen, Archana Singh-Manoux, Mika Kivimäki, Eniko Zsoldos, Miriam C Klein-Flügge, Sana Suri","doi":"10.1001/jamanetworkopen.2025.0171","DOIUrl":"10.1001/jamanetworkopen.2025.0171","url":null,"abstract":"<p><strong>Importance: </strong>Epidemiological studies suggest that lifestyle factors are associated with risk of dementia. However, few studies have examined the association of diet and waist to hip ratio (WHR) with hippocampus connectivity and cognitive health.</p><p><strong>Objective: </strong>To ascertain how longitudinal changes in diet quality and WHR during midlife are associated with hippocampal connectivity and cognitive function in later life.</p><p><strong>Design, setting, and participants: </strong>This cohort study analyzed data from participants in the Whitehall II Study at University College London (study inception: 1985) and Whitehall II Imaging Substudy at the University of Oxford (data collection: 2012-2016). Healthy participants from the Whitehall II Imaging Study with a mean age of 48 years at baseline to 70 years at magnetic resonance imaging (MRI) were included if they had information on diet from at least 1 wave, information on WHR from at least 2 waves, and good-quality MRI scans. Study analyses were completed from October 2019 to November 2024.</p><p><strong>Exposures: </strong>Diet quality was measured in participants(mean age, 48 years at baseline to 60 years) using the Alternative Healthy Eating Index-2010 score, which was assessed 3 times across 11 years. WHR was measured 5 times over 21 years in participants aged 48 to 68 years.</p><p><strong>Main outcomes and measures: </strong>White matter structural connectivity assessed using diffusion tensor imaging, hippocampal functional connectivity assessed using resting-state functional MRI, and cognitive performance measures. Brain imaging and cognitive tests were performed at a mean (SD) age of 70 (5) years.</p><p><strong>Results: </strong>The final diet quality sample comprised 512 participants (403 males [78.7%]; mean [SD] age, 47.8 [5.2] years), and the final WHR sample included 664 participants (532 males [80.1%]; mean [SD] age, 47.7 [5.1] years). Better diet quality in midlife and from midlife to late life was associated with higher hippocampal functional connectivity to the occipital lobe and cerebellum (left hippocampus: 9176 mm3, P < .05; left hippocampus and to the right cerebellum: 136 mm3, P = .04) and better white matter integrity as measured by higher fractional anisotropy (FA; 19 432 mm3, P < .05) and lower diffusivity (mean diffusivity [MD]: 5560 mm3, P < .05; axial diffusivity [AD]: 2600 mm3, P < .045; AD in fornix: β [SE] = 0.26 [0.11], false discovery rate-corrected P = .02). Higher WHR in midlife was associated with higher MD and radial diffusivity (covering 26.4% [333 088 mm3, P < .001] and 23.1% [291 888 mm3, P < .05], respectively, of the total white matter tracts in the cingulum and superior and inferior longitudinal fasciculus) and lower FA in the corticospinal tract (covering 4.9% of the white matter skeleton), including the inferior longitudinal fasciculus and cingulum (61 272 mm3, P < .05). Associations between midlife WHR, working memory, and ","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250171"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0107
Yunlin Feng, Min Jun, Amanda Y Wang, Song Ren, Steven D Weisbord, Rinaldo Bellomo, Marlies Ostermann, Clare Arnott, Martin Gallagher
{"title":"Predicting Contrast-Associated Acute Kidney Injury.","authors":"Yunlin Feng, Min Jun, Amanda Y Wang, Song Ren, Steven D Weisbord, Rinaldo Bellomo, Marlies Ostermann, Clare Arnott, Martin Gallagher","doi":"10.1001/jamanetworkopen.2025.0107","DOIUrl":"10.1001/jamanetworkopen.2025.0107","url":null,"abstract":"","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250107"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0160
Matthew J Molloy, Matthew Hall, Jessica L Markham, Jillian M Cotter, Elisha McCoy, Michael J Tchou, Megan E Collins, Michael J Steiner, John R Stephens, Andrew G Yu, Irma T Ugalde, Rustin B Morse, Monika K Goyal, Samantha A House
<p><strong>Importance: </strong>Respiratory pathogen testing has been a common deimplementation focus. The COVID-19 pandemic brought new considerations for respiratory testing; recent trends in testing rates are not well understood.</p><p><strong>Objective: </strong>To measure trends in respiratory testing among encounters for acute respiratory infections among children and adolescents (aged <18 years) from 2016 to 2023, assess the association of COVID-19 with these trends, and describe associated cost trends.</p><p><strong>Design, setting, and participants: </strong>This retrospective serial cross-sectional study included emergency department (ED) encounters and hospitalizations in US children's hospitals among children and adolescents with a primary acute infectious respiratory illness diagnosis. Data were ascertained from the Pediatric Health Information System database from January 1, 2016, to December 31, 2023.</p><p><strong>Exposure: </strong>Respiratory pathogen testing.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was the percentage of encounters with respiratory testing over time. Interrupted time series models were created to assess the association of COVID-19 with testing patterns. The inflation-adjusted standardized unit cost associated with respiratory testing was also examined.</p><p><strong>Results: </strong>There were 5 090 923 eligible encounters among patients who were children or adolescents (mean [SD] age, 3.36 [4.06] years); 55.0% of the patients were male. Among these encounters, 87.5% were ED only, 77.9% involved children younger than 6 years, and 94.5% involved children without complex chronic conditions. Respiratory testing was performed in 37.2% of all encounters. The interrupted time series models demonstrated increasing prepandemic testing rates in both ED-only encounters (slope, 0.26 [95% CI, 0.21-0.30]; P < .001) and hospitalizations (slope, 0.12 [95% CI, 0.07-0.16]; P < .001). Increases in respiratory testing were seen at the onset of the COVID-19 pandemic in both ED-only encounters (level change, 33.78 [95% CI, 31.77-35.79]; P < .001) and hospitalizations (level change, 30.97 [95% CI, 29.21-32.73]; P < .001), associated initially with COVID-19-only testing. Postpandemic testing rates remained elevated relative to prepandemic levels. The percentage of encounters with respiratory testing increased from 13.6% [95% CI, 13.5%-13.7%] in 2016 to a peak of 62.2% [95% CI, 62.1%-62.3%] in 2022. While COVID-19-only testing decreased after 2020, other targeted testing and large-panel (>5 targets) testing increased. The inflation-adjusted standardized unit cost associated with respiratory testing increased from $34.2 [95% CI, $33.9-$34.6] per encounter in 2017 to $128.2 [95% CI, $127.7-$128.6] per encounter in 2022.</p><p><strong>Conclusions and relevance: </strong>The findings of this cross-sectional study suggest that respiratory testing rates have increased over time, with large increases at the ons
{"title":"Trends in Respiratory Pathogen Testing at US Children's Hospitals.","authors":"Matthew J Molloy, Matthew Hall, Jessica L Markham, Jillian M Cotter, Elisha McCoy, Michael J Tchou, Megan E Collins, Michael J Steiner, John R Stephens, Andrew G Yu, Irma T Ugalde, Rustin B Morse, Monika K Goyal, Samantha A House","doi":"10.1001/jamanetworkopen.2025.0160","DOIUrl":"10.1001/jamanetworkopen.2025.0160","url":null,"abstract":"<p><strong>Importance: </strong>Respiratory pathogen testing has been a common deimplementation focus. The COVID-19 pandemic brought new considerations for respiratory testing; recent trends in testing rates are not well understood.</p><p><strong>Objective: </strong>To measure trends in respiratory testing among encounters for acute respiratory infections among children and adolescents (aged <18 years) from 2016 to 2023, assess the association of COVID-19 with these trends, and describe associated cost trends.</p><p><strong>Design, setting, and participants: </strong>This retrospective serial cross-sectional study included emergency department (ED) encounters and hospitalizations in US children's hospitals among children and adolescents with a primary acute infectious respiratory illness diagnosis. Data were ascertained from the Pediatric Health Information System database from January 1, 2016, to December 31, 2023.</p><p><strong>Exposure: </strong>Respiratory pathogen testing.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was the percentage of encounters with respiratory testing over time. Interrupted time series models were created to assess the association of COVID-19 with testing patterns. The inflation-adjusted standardized unit cost associated with respiratory testing was also examined.</p><p><strong>Results: </strong>There were 5 090 923 eligible encounters among patients who were children or adolescents (mean [SD] age, 3.36 [4.06] years); 55.0% of the patients were male. Among these encounters, 87.5% were ED only, 77.9% involved children younger than 6 years, and 94.5% involved children without complex chronic conditions. Respiratory testing was performed in 37.2% of all encounters. The interrupted time series models demonstrated increasing prepandemic testing rates in both ED-only encounters (slope, 0.26 [95% CI, 0.21-0.30]; P < .001) and hospitalizations (slope, 0.12 [95% CI, 0.07-0.16]; P < .001). Increases in respiratory testing were seen at the onset of the COVID-19 pandemic in both ED-only encounters (level change, 33.78 [95% CI, 31.77-35.79]; P < .001) and hospitalizations (level change, 30.97 [95% CI, 29.21-32.73]; P < .001), associated initially with COVID-19-only testing. Postpandemic testing rates remained elevated relative to prepandemic levels. The percentage of encounters with respiratory testing increased from 13.6% [95% CI, 13.5%-13.7%] in 2016 to a peak of 62.2% [95% CI, 62.1%-62.3%] in 2022. While COVID-19-only testing decreased after 2020, other targeted testing and large-panel (>5 targets) testing increased. The inflation-adjusted standardized unit cost associated with respiratory testing increased from $34.2 [95% CI, $33.9-$34.6] per encounter in 2017 to $128.2 [95% CI, $127.7-$128.6] per encounter in 2022.</p><p><strong>Conclusions and relevance: </strong>The findings of this cross-sectional study suggest that respiratory testing rates have increased over time, with large increases at the ons","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250160"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1001/jamanetworkopen.2025.0562
Xiaoyi Xu, Jiseon Kwon, Ruiqi Yan, Catherine Apio, Soomin Song, Gyujin Heo, Qijun Yang, Jigyasha Timsina, Menghan Liu, John Budde, Kaj Blennow, Henrik Zetterberg, Alberto Lleó, Agustin Ruiz, José Luis Molinuevo, Virginia Man-Yee Lee, Yuetiva Deming, Amanda J Heslegrave, Tim J Hohman, Pau Pastor, Elaine R Peskind, Marilyn S Albert, John C Morris, Taesung Park, Carlos Cruchaga, Yun Ju Sung
<p><strong>Importance: </strong>Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of APOE in AD varies with sex and ancestry. While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.</p><p><strong>Objective: </strong>To systematically investigate the association of sex and APOE-ε4 with 3 core CSF biomarkers across ancestries.</p><p><strong>Design, setting, and participants: </strong>This cohort study examined 3 CSF biomarkers (amyloid β1-42 [Aβ42], phosphorylated tau 181 [p-tau], and total tau, in participants from 20 cohorts from July 1, 1985, to March 31, 2020. These individuals were grouped into African, Asian, and European ancestries based on genetic data. Data analyses were conducted from June 1, 2023, to November 10, 2024.</p><p><strong>Exposure: </strong>Sex (male or female) and APOE-ε4.</p><p><strong>Main outcomes and measures: </strong>The associations of sex and APOE-ε4 with biomarker levels were assessed within each ancestry group, adjusting for age. Meta-analyses were performed to identify these associations across ancestries. Sensitivity analyses were conducted to exclude the potential influence of the APOE-ε2 allele.</p><p><strong>Results: </strong>This cohort study included 4592 individuals (mean [SD] age, 70.8 [10.2] years; 2425 [52.8%] female; 119 [2.6%] African, 52 [1.1%] Asian, and 4421 [96.3%] European). Higher APOE-ε4 dosage scores were associated with lower Aβ42 values (β [SE], -0.58 [0.02], P < .001), indicating more severe pathology; these associations were seen in men and women separately and jointly. The association with APOE-ε4 was statistically greater in men (β [SE], -0.63 [0.03]; P < .001) vs women (β [SE], -0.52 [0.03]; P < .001) of European ancestry (P = .01 for interaction). Women had higher levels of p-tau, indicating more severe neurofibrillary pathology. The association between APOE-ε4 dosage and p-tau was in the expected direction (higher APOE-ε4 dosage for higher p-tau values) in both sexes, but the difference between sexes was significant only in those of African ancestry (β [SE], 0.10 [0.18]; P = .57 for men; β [SE], 0.66 [0.17]; P < .001 for women; P = .03 for interaction). Women also had higher levels of total tau, indicating more neuronal damage. The association between APOE-ε4 dosage and total tau was stronger in women than in men in the African cohort (β [SE], 0.20 [0.22]; P = .36 for men and β [SE], 0.65 [0.22], P = .004 for women [P = .16 for interaction]) and European cohort (β [SE], 0.36 [0.03]; P < .001 in women and β [SE], 0.27 [0.03], P < .001 in men [P = .053 for interaction]); no significant associations were found in the Asian cohort. Sensitivity analysis excluding APOE-ε2 carriers yielded similar results.</
{"title":"Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries.","authors":"Xiaoyi Xu, Jiseon Kwon, Ruiqi Yan, Catherine Apio, Soomin Song, Gyujin Heo, Qijun Yang, Jigyasha Timsina, Menghan Liu, John Budde, Kaj Blennow, Henrik Zetterberg, Alberto Lleó, Agustin Ruiz, José Luis Molinuevo, Virginia Man-Yee Lee, Yuetiva Deming, Amanda J Heslegrave, Tim J Hohman, Pau Pastor, Elaine R Peskind, Marilyn S Albert, John C Morris, Taesung Park, Carlos Cruchaga, Yun Ju Sung","doi":"10.1001/jamanetworkopen.2025.0562","DOIUrl":"10.1001/jamanetworkopen.2025.0562","url":null,"abstract":"<p><strong>Importance: </strong>Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of APOE in AD varies with sex and ancestry. While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.</p><p><strong>Objective: </strong>To systematically investigate the association of sex and APOE-ε4 with 3 core CSF biomarkers across ancestries.</p><p><strong>Design, setting, and participants: </strong>This cohort study examined 3 CSF biomarkers (amyloid β1-42 [Aβ42], phosphorylated tau 181 [p-tau], and total tau, in participants from 20 cohorts from July 1, 1985, to March 31, 2020. These individuals were grouped into African, Asian, and European ancestries based on genetic data. Data analyses were conducted from June 1, 2023, to November 10, 2024.</p><p><strong>Exposure: </strong>Sex (male or female) and APOE-ε4.</p><p><strong>Main outcomes and measures: </strong>The associations of sex and APOE-ε4 with biomarker levels were assessed within each ancestry group, adjusting for age. Meta-analyses were performed to identify these associations across ancestries. Sensitivity analyses were conducted to exclude the potential influence of the APOE-ε2 allele.</p><p><strong>Results: </strong>This cohort study included 4592 individuals (mean [SD] age, 70.8 [10.2] years; 2425 [52.8%] female; 119 [2.6%] African, 52 [1.1%] Asian, and 4421 [96.3%] European). Higher APOE-ε4 dosage scores were associated with lower Aβ42 values (β [SE], -0.58 [0.02], P < .001), indicating more severe pathology; these associations were seen in men and women separately and jointly. The association with APOE-ε4 was statistically greater in men (β [SE], -0.63 [0.03]; P < .001) vs women (β [SE], -0.52 [0.03]; P < .001) of European ancestry (P = .01 for interaction). Women had higher levels of p-tau, indicating more severe neurofibrillary pathology. The association between APOE-ε4 dosage and p-tau was in the expected direction (higher APOE-ε4 dosage for higher p-tau values) in both sexes, but the difference between sexes was significant only in those of African ancestry (β [SE], 0.10 [0.18]; P = .57 for men; β [SE], 0.66 [0.17]; P < .001 for women; P = .03 for interaction). Women also had higher levels of total tau, indicating more neuronal damage. The association between APOE-ε4 dosage and total tau was stronger in women than in men in the African cohort (β [SE], 0.20 [0.22]; P = .36 for men and β [SE], 0.65 [0.22], P = .004 for women [P = .16 for interaction]) and European cohort (β [SE], 0.36 [0.03]; P < .001 in women and β [SE], 0.27 [0.03], P < .001 in men [P = .053 for interaction]); no significant associations were found in the Asian cohort. Sensitivity analysis excluding APOE-ε2 carriers yielded similar results.</","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 3","pages":"e250562"},"PeriodicalIF":10.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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