Large Population-based Cohort Research Articles

Cardiovascular and mortality outcomes with GLP-1 receptor agonists vs other glucose-lowering drugs in individuals with NAFLD and type 2 diabetes: a large population-based matched cohort study.

We aimed to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus decreases the risk of new-onset adverse cardiovascular events (CVEs) and mortality rate compared with other glucose-lowering drugs in a real setting at a population level. We conducted a population-based propensity-matched retrospective cohort study using TriNetX. The cohort comprised patients over 20 years old who were newly treated with glucose-lowering drugs between 1 January 2013 and 31 December 2021, and followed until 30 September 2022. New users of GLP-1RAs were matched based on age, demographics, comorbidities and medication use by using 1:1 propensity matching with other glucose-lowering drugs. The primary outcome was the new onset of adverse CVEs, including heart failure, composite incidence of major adverse cardiovascular events (MACE; defined as unstable angina, myocardial infarction, or coronary artery procedures or surgeries) and composite cerebrovascular events (defined as the first occurrence of stroke, transient ischaemic attack, cerebral infarction, carotid intervention or surgery), and the secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate HRs. The study involved 2,835,398 patients with both NAFLD and type 2 diabetes. When compared with the sodium-glucose cotransporter 2 (SGLT2) inhibitors group, the GLP-1RAs group showed no evidence of a difference in terms of new-onset heart failure (HR 0.97; 95% CI 0.93, 1.01), MACE (HR 0.95; 95% CI 0.90, 1.01) and cerebrovascular events (HR 0.99; 95% CI 0.94, 1.03). Furthermore, the two groups had no evidence of a difference in mortality rate (HR 1.06; 95% CI 0.97, 1.15). Similar results were observed across sensitivity analyses. Compared with other second- or third-line glucose-lowering medications, the GLP-1RAs demonstrated a lower rate of adverse CVEs, including heart failure (HR 0.88; 95% CI 0.85, 0.92), MACE (HR 0.89; 95% CI 0.85, 0.94), cerebrovascular events (HR 0.93; 95% CI 0.89, 0.96) and all-cause mortality rate (HR 0.70; 95% CI 0.66, 0.75). In individuals with NAFLD and type 2 diabetes, GLP-1RAs are associated with lower incidences of adverse CVEs and all-cause mortality compared with metformin or other second- and third-line glucose-lowering medications. However, there was no significant difference in adverse CVEs or all-cause mortality when compared with those taking SGLT2 inhibitors.

The relationship between familial-genetic risk and pharmacological treatment in a Swedish national sample of patients with major depression, bipolar disorder, and schizophrenia.

Using Swedish registers, we examine whether the prescription of and the response to antidepressants (AD), mood stabilizers (MS), and antipsychotics (AP) in the treatment of, respectively, major depression (MD), bipolar disorder (BD), and schizophrenia (SZ), are influenced by familial-genetic risk. We examined individuals born in Sweden 1960-1995 with a first diagnosis of MD (n = 257,177), BD (n = 23,032), and SZ (n = 4248) from 2006 to 2018. Drug classes and Defined Daily Dose (DDD) were obtained from the Pharmacy register using the Anatomical Therapeutic Chemical system. We utilized the Familial Genetic Risk Scores (FGRS) calculated from morbidity risks in first- through fifth degree relatives. Treatment with antidepressants (AD) in MD, mood-stabilizers (MS) in BD, and antipsychotics (AP) in SZ were associated with significantly higher disorder-specific familial-genetic risks. Using dosage trajectory analysis of AD, MS, and AP treatment for MD, BD, and SZ, respectively, familial-genetic risk was positively associated with higher and/or increasing drug dosages over time. For MD and BD, examining cases started on the most common pharmacologic treatment class (SSRIs for MD and "other anti-epileptics" for BD), familial-genetic risks were significantly lower in those who did not versus did later receive treatment from other AD and MS classes, respectively. Higher familial-genetic risk for BD predicted switching AD medication in cases of MD. Among pharmacologically treated cases of BD, familial-genetic risk was significantly higher for those treated with lithium. In a large population-based patient cohort, we found evidence of a wide-spread association between higher familial-genetic risk and i) increased likelihood of receiving pharmacologic treatment but 2) responding more poorly to it-as indicated by a switching of medications -- and/or requiring higher doses. Further investigations into the clinical utility of genetic risk scores in the clinical managements of MD, BD, and SZ are warranted.

Semiautomatic Assessment of Facet Tropism From Lumbar Spine MRI Using Deep Learning: A Northern Finland Birth Cohort Study.

This is a retrospective, cross-sectional, population-based study that automatically measured the facet joint (FJ) angles from T2-weighted axial magnetic resonance imagings (MRIs) of the lumbar spine using deep learning (DL). This work aimed to introduce a semiautomatic framework that measures the FJ angles using DL and study facet tropism (FT) in a large Finnish population-based cohort. T2-weighted axial MRIs of the lumbar spine (L3/4 through L5/S1) for (n=1288) in the NFBC1966 Finnish population-based cohort were used for this study. A DL model was developed and trained on 430 participants' MRI images. The authors computed FJ angles from the model's prediction for each level, that is, L3/4 through L5/S1, for the male and female subgroups. Inter-rater and intrarater reliability was analyzed for 60 participants using annotations made by two radiologists and a musculoskeletal researcher. With the developed method, we examined FT in the entire NFBC1966 cohort, adopting the literature definitions of FT thresholds at 7° and 10°. The rater agreement was evaluated both for the annotations and the FJ angles computed based on the annotations. FJ asymmetry ( - was used to evaluate the agreement and correlation between the raters. Bland-Altman analysis was used to assess the agreement and systemic bias in the FJ asymmetry. The authors used the Dice score as the metric to compare the annotations between the raters. The authors evaluated the model predictions on the independent test set and compared them against the ground truth annotations. This model scored Dice (92.7±0.1) and intersection over union (87.1±0.2) aggregated across all the regions of interest, that is, vertebral body (VB), FJs, and posterior arch (PA). The mean FJ angles measured for the male and female subgroups were in agreement with the literature findings. Intrarater reliability was high, with a Dice score of VB (97.3), FJ (82.5), and PA (90.3). The inter-rater reliability was better between the radiologists with a Dice score of VB (96.4), FJ (75.5), and PA (85.8) than between the radiologists and the musculoskeletal researcher. The prevalence of FT was higher in the male subgroup, with L4/5 found to be the most affected region. The authors developed a DL-based framework that enabled us to study FT in a large cohort. Using the proposed method, the authors present the prevalence of FT in a Finnish population-based cohort.

Urban greenspaces and child blood pressure in China: Evidence from a large population-based cohort study

BackgroundWith the world's population steadily shifting toward urban living, children's engagement with the natural environment seems to be diminishing. This raises significant concerns about the influence of urban greenspaces on the cardiovascular health of children. ObjectiveTo assess the association between urban greenspaces exposure and blood pressure (BP) in Chinese primary schoolchildren. MethodsThis prospective cohort study used data from the Children's growth environment, lifestyle, physical, and mental health development (COHERENCE) project in Guangzhou, China. Participants included 164,853 primary schoolchildren starting from 2016/17 to 2019/20 academic year. We assessed the surrounding greenspaces at home and school by using Sentinel-2 satellite data on the normalized difference vegetation index. Prehypertension and hypertension status were defined with BP above 90th to less than the 95th percentile, at or above the 95th percentile, respectively. The association of surrounding greenness with children's BP levels and risk of prehypertension/hypertension were examined using linear mixed-effects models and Cox proportional hazards model. ResultsAmong 164,853 eligible children aged 7.21 (0.74) years, 89,190 (54.1%) were boys. Our results showed that average systolic and diastolic BP increased by 0.48 and 0.42 standard deviations, respectively, over the 3-year follow-up. We identified 23,225 new cases of prehypertension and 35,067 of hypertension status. An interquartile range increase both in home-, school- and home-school NDVI100m was significantly associated with a reduction of 0.018–0.037 in BP z-scores and a 2.7%–7.6% lower risk of hypertension. Additionally, family socioeconomic status modified the impact of home-school greenness on BP levels. Air pollution exhibited mediating effects solely in school-greenness-BP associations, while physical activity and children's BMI mainly mediated the relationships between home-greenness and BP. ConclusionThe findings of this large cohort study suggest that surrounding greenspaces are associated with lower BP levels and a decreased risk of prehypertension and hypertension in Chinese schoolchildren.

TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma.

Treatment resistance and relapse are common problems in head and neck squamous cell carcinoma (HNSCC). Except for p16, no clinically accepted prognostic biomarkers are available for HNSCC. New biomarkers predictive of recurrence and survival are crucial for optimal treatment planning and patient outcome. High translocator protein (TSPO) levels have been associated with poor survival in cancer, but the role of TSPO has not been extensively evaluated in HNSCC. TSPO expression was determined in a large population-based tissue microarray cohort including 611 patients with HNSCC and evaluated for survival in several clinicopathological subgroups. A TCGA HNSCC cohort was used to further analyze the role of TSPO in HNSCC. TSPO expression was downregulated in more aggressive tumors. Low TSPO expression associated with worse 5-year survival and was an independent prognostic factor for disease-specific survival. Subgroup analyses showed that low TSPO expression associated with worse survival particularly in p16-positive oropharyngeal cancer. In silico analyses supported the prognostic role of TSPO. Cellular respiration had the highest significance in pathway analyses for genes expressed positively with TSPO. Decreased TSPO expression associates with poor prognosis in HNSCC. TSPO is a prognostic biomarker in HNSCC to potentially guide treatment stratification especially in p16-positive oropharyngeal cancer.

Performance of Prediction Models for Esophageal Squamous Cell Carcinoma in General Population: A Systematic Review and External Validation Study.

Prediction models for esophageal squamous cell carcinoma (ESCC) need to be proven effective in the target population before they can be applied to population-based endoscopic screening to improve cost-effectiveness. We have systematically reviewed ESCC prediction models applicable to the general population and performed external validation and head-to-head comparisons in a large multicenter prospective cohort including 5 high-risk areas of China (Fei Cheng, Lin Zhou, Ci Xian, Yang Zhong, and Yan Ting). Models were identified through a systematic review and validated in a large population-based multicenter prospective cohort that included 89,753 participants aged 40-69 years who underwent their first endoscopic examination between April 2017 and March 2021 and were followed up until December 31, 2022. Model performance in external validation was estimated based on discrimination and calibration. Discrimination was assessed by C-statistic (concordance statistic), and calibration was assessed by calibration plot and Hosmer-Lemeshow test. The systematic review identified 15 prediction models that predicted severe dysplasia and above lesion (SDA) or ESCC in the general population, of which 11 models (4 SDA and 7 ESCC) were externally validated. The C-statistics ranged from 0.67 (95% confidence interval 0.66-0.69) to 0.70 (0.68-0.71) of the SDA models, and the highest was achieved by Liu et al (2020) and Liu et al (2022). The C-statistics ranged from 0.51 (0.48-0.54) to 0.74 (0.71-0.77), and Han et al (2023) had the best discrimination of the ESCC models. Most models were well calibrated after recalibration because the calibration plots coincided with the x = y line. Several prediction models showed moderate performance in external validation, and the prediction models may be useful in screening for ESCC. Further research is needed on model optimization, generalization, implementation, and health economic evaluation.

Low-level exposure to lead and atherosclerosis in the carotid arteries: Results from the Swedish population-based cohort SCAPIS

BackgroundLead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. AimTo investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. MethodsWe performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013–2018. Blood lead (B–Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B–Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. ResultsAtherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2–222). The median B–Pb concentration was 14 μg/L (range: 0.75–203). After adjusting for potential confounders, individuals in the fourth quartile of B–Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 μg/L increase in B–Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). ConclusionsThis study shows an association between B–Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.

Overview of Diabetes as a Risk Factor for Developing Dementia: A Systematic Review

Background: There is debate over the relationship between diabetes and the main forms of dementia. The cognitive alterations associated with type 2 diabetes (T2D) mostly impact mental flexibility, mental speed, and learning and memory.
 Objectives: To ascertain the degree of the link between diabetes and dementia, we thoroughly reviewed papers on the incidence of dementia in individuals with diabetes mellitus in this study.
 Methods: PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process.
 Results and Interpretation: We included ten studies with a total of 173797 participants, and 78828 (45.4%) were males. All of the included studies were prospective cohorts. For diabetic patients, early-onset diabetes, poor glycemic management, and diabetes status are risk factors for dementia development. There was also a higher chance of dementia development in those with mild to severe motor cognitive impairment and hereditary variables. Longitudinal studies that involve comprehensive evaluations of comorbid diseases and diabetes-related variables, as well as rigorous assessments of cognition—ideally in conjunction with neuroimaging—will be necessary for this process. This method will work best with large population-based cohort studies of older adults with diabetes and with longitudinal studies of at-risk groups that look at the development of diabetes, metabolic syndrome, vascular disease, and cognitive decline.

P140: Midlife diet and risk of dementia/mild cognitive impairment

The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake was assessed on two occasions: in the years 1995 and 2000 (aged 45-64 in 1995). In 2014-2015, approximately 1300 participants from Saku district in Nagano prefecture completed a mental health screening including later life depression and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). We used logistic regression analyses to calculate odds ratios (ORs) for MCI and dementia. Based on this survey, we found the following characteristics of midlife diet, which may be useful information to prevent cognitive decline/dementia.1.High-density lipoprotein cholesterol (HDL-C) and later cognitive decline (Svensson et al. Transl Psychiatry, 2019): Midlife high-density lipoprotein cholesterol (HDL-C) is a measure which could help identify individuals at reduced risk of developing age-related cognitive decline. Compared to the lowest HDL-C quartile, the highest HDL-C quartile was significantly inversely associated with MCI. High HDL-C (quartiles 2-4) was inversely associated with dementia compared to low HDL-C (quartile 1).2.Dietary fish and n-3 polyunsaturated fatty acid (PUFA) and later cognitive decline (Nozaki et al. J Alzheimers Dis, 2021): Higher intake of fish, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in midlife significantly reduced risks of dementia.3.Intake of soy and the isoflavone and later cognitive decline (Svensson et al. J Alzheimers Dis, 2021): Compared to the lowest dietary quartile of energy-adjusted isoflavone genistein intake, the highest quartile was significantly associated with late-life cognitive impairment.4.Cancer/diabetes and later cognitive decline (Sadahiro et al. Psychiatry Clin Neurosci, 2019): Comorbid cancer and diabetes from midlife may increase the risk of MCI or dementia in later life. In addition to the increased dementia risk associated with diabetes on the basis of insulin resistance, cancer and cancer therapies may also interfere with cognitive function via insulin resistance.

Multimorbidity of cardiovascular disease subtypes in a prospective cohort of 1.2 million UK women

ObjectiveCardiovascular multimorbidity (CVM) is the co-occurrence of multiple cardiovascular disease subtypes (CVDs) in one person. Because common patterns and incidence of CVM are not well-described, particularly in women, we conducted...

Association of circulating vitamin D and omega 3 fatty acid with all-cause mortality in patients with rheumatoid arthritis: A large population-based cohort study.

To assess the associations of both the level of circulating vitamin D and the ratio of omega-3 fatty acids to total fatty acids (omega-3%) with mortality among participants with rheumatoid arthritis. This study included 4,293 and 1,157 adults with rheumatoid arthritis identified by self-report from the UK Biobank for the analysis of vitamin D and omega-3%, respectively. Death outcomes were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland). Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for mortality. The medians (25th-75th percentiles) of serum 25(OH)D and omega-3% were 45.8 (31.4-62.9) nmol/L and 4.1% (3.3%-5.1%), respectively. During 52,612 person-years of follow-up in the 25(OH)D group, 502 all-cause deaths occurred; and during 14,192 person-years of follow-up in the omega-3% group, 122 all-cause deaths occurred. Rheumatoid arthritis patients with vitamin D levels of at least 20nmol/L had an approximately 40-50% lower risk of all-cause mortality than those with severe vitamin D deficiency (hazard ratio ranging from 0.51 to 0.62, all P values<0.05). Each unit increase in natural log-transformed 25(OH)D was associated with a 22% reduction in the risk of all-cause mortality, and a U-shaped association between serum 25(OH)D and all-cause mortality was found. However, the association between omega-3% and mortality was not significant. Lower serum 25(OH)D concentration, but not omega-3%, was significantly associated with higher all-cause mortality in patients with rheumatoid arthritis. Optimizing serum vitamin D levels may be an important factor in reducing mortality risk in this population.

The association between serum 25-hydroxyvitamin D levels and psoriasis in a large population-based cohort: across-sectional analysis of The Tromsø Study 2015-16.

Case-control studies indicate an association between lower serum 25-hydroxyvitamin D [25(OH)D] levels and psoriasis. Data from larger population-based cohorts including mild cases are sparse. To investigate the association between 25(OH)D and psoriasis in a large population-based cohort, and assess possible effect modification by overweight. Data from the Tromsø Study 2015-16 (Tromsø7), which included 19 520 participants from the general population aged 40-79 years, were subjected to a cross-sectional analysis. We assessed the shapes of the relationships between 25(OH)D and psoriasis using fractional polynomials. Odds ratios (ORs) for lifetime and active psoriasis were estimated using logistic regression. Adjusted models included month of blood sampling, body mass index (BMI), age and sex. Two-way and additive interaction between BMI and 25(OH)D were explored. From a total of 19 520 participants [10 203 women (52.3%); mean age 56.3 years (SD 10.4); mean 25[OH]D, 63.4 nmol L-1 (SD 21.9)], 2088 (10.7%) reported lifetime psoriasis and 1179 (6.0%) reported active psoriasis the past 12 months. There was no association between 25(OH)D and lifetime psoriasis [OR per 10 nmol L-1 increase in 25(OH)D 1.02, 95% confidence interval (CI) 0.99-1.04]. The relationship between 25(OH)D and active psoriasis was suggested to be nonlinear, but the model was not significant (P = 0.098). There was evidence for a superadditive effect (i.e. larger than the sum of the factors) of BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1 on the odds for active psoriasis (OR 1.92, 95% CI 1.18-3.12), but not for lifetime psoriasis (OR 1.41, 95% CI 0.93-2.15). There was no evidence for two-way interaction between BMI and 25(OH)D. This large population-based study found no significant relationship between 25(OH)D and psoriasis. The analysis may have been underpowered to detect a threshold effect in the lower 25(OH)D spectrum. Interaction analysis indicates that high BMI and vitamin D deficiency combined increase the odds of active psoriasis more than the sum of these factors, with an estimated 92% higher odds for active psoriasis in participants with BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1. Providing advice to prevent vitamin D deficiency may be considered in the follow-up of overweight patients with psoriasis.

Prospective Real-World Outcomes of Acute Myeloid Leukemia

Background: It is evident that treatment outcomes improve with the clinical studies, in this study we aimed to investigate the demographics and treatment modalities of the acute myeloid leukemia (AML) patients in a large population-based cohort who were diagnosed and followed up in Turkey as a real-world data. Methods: All AML adult patients who were recorded on the database of Turkish AML Registry project from 25 sites were included in this study if they were diagnosed before 1st of June 2022. Study approved by ethics committee and Ministry of Health of Turkey. Demographics and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. Results: A total of 906 patients were included in the study, 891 patients data accepted as adequate and underwent further evaluation. Median follow-up period was 12.0 (SD:26.6) months and 45.4% of the patients were female. Median age at the time of diagnosis was 58 (18-91). According to the FAB classification most common subtypes were M4 (23.6%), M2 (21.6%), M5 (16.8%) and M1 (13.5%) and AML, NOS (36.9%) is the most common type according to the WHO classification. Of the patients 60.8%, 24.7%, 14.5%, was intermediate, favorable and poor respectively considering AML risk stratification (ELN 2017) by genetics. Only 4.4% of the patients had extramedullary involvement. For the first induction 70.8% of the patients had received intensive regimens composing anthracyclines and ARA-C and for the first relapse 71.8%. ARA-C (71.7%) backbone and Azacitidine alone (13.4%) are the most used regimens, 10.5% and 22.5% underwent allo-HCT during the first and second induction respectively. Response rates obtained by the induction therapies were as follows; 61.7% CR (including 9.3% MLFS), 14.2% PR, 8.6% SD, 15.5% PD, the ratio was 59.7% and 24.3% for CR2 and PD respectively. Median overall survival has not been reached for the favorable risk group, were 16.2 months for the intermediate risk and 14.1 months for the poor risk group (p&amp;lt;0.001) and 22.7 months for the entire population. Median progression free survival were 32.6 months for the favorable risk group, 12.7 months for the intermediate risk and 9.4 months for the poor risk group (p&amp;lt;0.001) and 15.2 months for the entire population (Figure 1). COX regression analysis were performed for the prognostic factors of OS, univariate analysis performed with the parameters; age (&amp;lt;60 and ≥60), FAB classification, ECOG, FLT3, NMP1, HCT were accepted as clinically significant covariates. First univariate then with the significant parameters (p&amp;lt;0.05) multivariate COX regression analysis were perfomed. With the multivariate analysis age (p:0.005, HR:2.140, 95% CI: 1.254-3.653), FAB classification (favorable were reference, intermediate p:0.045, HR: 2.269, 95% CI: 1.017-5.064, poor p:0.217, HR: 2.105, 95% CI: 6.858) and HCT (p:0.034, HR:2.618, 95% CI: 1.073-6.387) were found as significant. Conclusion: Progression free survival obtained after induction therapy and overall survival were relatively shorter than the ones which were presented by other real-world registries. Lack of early access to the targeted and novel agents, like Flt3 inhibitors, Venetoclax, IDH1 and 2 inhibitors, CPX351 and Glasdegib should be a potential explanation to this relatively short PFS and OS. We have also been aware of un-ideal access to well established and nation wide cytogenetic laboratory service to induce early integration of targeted agents to the treatment and better risk stratification to determine the patients who should obtain the best prolonged survival via allo-HCT.

A population-based cohort study of electronic tolling, traffic congestion, and adverse birth outcomes

BackgroundAlthough traffic-related air pollution is largely regulated at the federal level, congestion reduction projects may reduce local traffic and air pollution to levels that create positive co-benefits for population health. In recent years, many urban areas have implemented electronic tolling systems to improve traffic conditions. ObjectiveQuantify associations between implementing electronic tolling and local changes in traffic and infant health. MethodsUsing a population-based birth cohort (Texas, 1999–2016), we calculated residential proximity to the nearest tolled road segment within 5 km (n = 625,279) and examined changes in local traffic before and after toll implementation. Using a difference-in-differences design, we compared four markers of adverse birth outcomes (term birth weight, term low birth weight, preterm birth, very preterm birth) among infants from pregnant people residing < 0.5 km from a road segment before and after the tolls were implemented and compared them to a contemporaneous population of pregnant people residing at 2–5 km. ResultsWe observed minimal changes in local traffic after the implementation of tolling. Among births within 500 m of a tolled road, we found little evidence of an association between the implementation of tolling and adverse birth outcomes (term birth weight [β: −4.5, 95 % CI: −11.7, 2.6], term low birth weight [OR: 1.00, 95 % CI: 0.89, 1.13], preterm birth [OR: 0.99, 95 % CI: 0.92, 1.05], very preterm birth [OR: 1.00, 95 % CI: 0.84, 1.18]), compared to the contemporaneous control group of births at 2–5 km. In sub-analyses, we found some evidence of a reduced association between toll booth removal and preterm birth (OR: 0.84, 95 % CI: 0.70, 1.01) but not for other outcomes or tolling types. DiscussionIn this large population-based retrospective cohort study of births in Texas, we found little evidence that the implementation of tolling was consistently associated with improvements in local infant health outcomes.

Factors Associated With Length of Stay for Hip and Knee Arthroplasty: A 20-Year Single-Province Population-Based Analysis of Longitudinal Temporal Trends

BackgroundWith notable benefits in reducing length of stay (LOS), this study aimed to quantify the temporal trend and the factors contributing to increased LOS for primary and revision total hip (THA and rTHA) and knee (TKA and rTKA) arthroplasty. The study was carried out for a large population-based cohort over a 20-year period. MethodsThis was a retrospective population-based study assessing the LOS for all primary and revision THA and TKA procedures between 2003 and 2022. The primary outcome of interest was LOS. Univariate and multivariate analyses were performed to identify associated variables. ResultsFor the entire dataset, there were 16,677 primary THAs, 13,018 primary TKAs, 3276 (aseptic) rTHAs, 1445 (aseptic) rTKAs, 820 (septic) rTHAs, and 667 (septic) rTKAs. The median LOS over the 20-year period between 2003 and 2022 demonstrated a steady and continuous decline from a median of 5 days (interquartile range 3-7) in 2003 to 1 day (interquartile range 1-2) in 2022. On multivariate analysis, there were a number of factors associated with increasing LOS: year of procedure (P < .0001), procedure type (P < .0001), age (P < .0001), and American Society of Anesthesiologists class (P < .0001). On multivariate analysis, body mass index was not associated with increased LOS (P = .5631). ConclusionsThere was a downward trend in LOS for all types of primary and revision THA and TKA. The factors contributing most to a reduction in LOS include the year the procedure was performed, primary THA procedures, aseptic (vs periprosthetic joint infection) revision procedures, younger age, and lower American Society of Anesthesiologists classes.

Noninvasive Staging of Lymph Node Status in Breast Cancer Using Machine Learning: External Validation and Further Model Development.

Most patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using postoperative data or imaging features that are not part of the diagnostic workup. Lymphovascular invasion (LVI) is a top-ranked predictor of nodal metastasis; however, its preoperative assessment is challenging. This paper aimed to externally validate a multilayer perceptron (MLP) model for noninvasive lymph node staging (NILS) in a large population-based cohort (n=18,633) and develop a new MLP in the same cohort. Data were extracted from the Swedish National Quality Register for Breast Cancer (NKBC, 2014-2017), comprising only routinely and preoperatively available documented clinicopathological variables. A secondary aim was to develop and validate an LVI MLP for imputation of missing LVI status to increase the preoperative feasibility of the original NILS model. Three nonoverlapping cohorts were used for model development and validation. A total of 4 MLPs for nodal status and 1 LVI MLP were developed using 11 to 12 routinely available predictors. Three nodal status models were used to account for the different availabilities of LVI status in the cohorts and external validation in NKBC. The fourth nodal status model was developed for 80% (14,906/18,663) of NKBC cases and validated in the remaining 20% (3727/18,663). Three alternatives for imputation of LVI status were compared. The discriminatory capacity was evaluated using the validation area under the receiver operating characteristics curve (AUC) in 3 of the nodal status models. The clinical feasibility of the models was evaluated using calibration and decision curve analyses. External validation of the original NILS model was performed in NKBC (AUC 0.699, 95% CI 0.690-0.708) with good calibration and the potential of sparing 16% of patients with node-negative disease from SLNB. The LVI model was externally validated (AUC 0.747, 95% CI 0.694-0.799) with good calibration but did not improve the discriminatory performance of the nodal status models. A new nodal status model was developed in NKBC without information on LVI (AUC 0.709, 95% CI: 0.688-0.729), with excellent calibration in the holdout internal validation cohort, resulting in the potential omission of 24% of patients from unnecessary SLNBs. The NILS model was externally validated in NKBC, where the imputation of LVI status did not improve the model's discriminatory performance. A new nodal status model demonstrated the feasibility of using register data comprising only the variables available in the preoperative setting for NILS using machine learning. Future steps include ongoing preoperative validation of the NILS model and extending the model with, for example, mammography images.

Accuracy of self-reported diagnoses of polymyalgia rheumatica and giant cell arteritis in the French prospective E3N- EPIC cohort: A validation study

ObjectivesTo assess the accuracy of self-reported giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) diagnoses in a large French population-based prospective cohort, and to devise algorithms to improve their accuracy. MethodsThe E3N-EPIC cohort study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale) includes 98,995 French women born between 1925 and 1950, recruited in 1990 to study risk factors of cancer and chronic diseases. They completed biennially mailed questionnaires to update their health-related information and lifestyle characteristics. In three questionnaires, women could self-report a diagnosis of GCA/PMR. Those women were additionally sent a specific questionnaire, designed to ascertain self-reported diagnoses of GCA/PMR. Four algorithms were then devised to improve their identification. Accuracies of self-reported diagnoses and of each algorithm were calculated by comparing the diagnoses with a blinded medical chart review. ResultsAmong 98,995 participants, 1,392 women self-reported GCA/PMR. 830 women sent back the specific questionnaire, and 202 women provided medical charts. After independent review of the 202 medical charts, 87.6 % of the self-reported diagnoses of GCA/PMR were accurate. Using additional data from a specific questionnaire (diagnosis confirmation by a physician, and self-report of >3-month of glucocorticoids), and from a reimbursement database (at least two deliveries of glucocorticoids in less than 3 consecutive months) improved their accuracy (91.8 % to 92.8 %). ConclusionThe accuracy of self-reported diagnosis of GCA/PMR was high in the E3N-cohort but using additional data as a specific GCA/PMR questionnaire and/or corticosteroid reimbursement database further improved this accuracy. With nearly 600 detected cases of GCA/PMR, we will be able to investigate risk factors for GCA/PMR in women.

Comparing Costs of Noninvasive Cardiac Diagnostic Tests—a Population-Based Study

Noninvasive cardiac diagnostic tests (NITs) for the diagnosis of coronary artery disease have been estimated to cost >$3 billion annually in the United States alone and have recently undergone scrutiny over concerns of overuse. Consequently, comparing costs of different NIT testing strategies is of urgent importance to health care planning. We utilized population-based administrative and clinical data from Ontario, Canada, to compare downstream costs between 4 available NIT testing strategies (graded exercise stress testing [GXT], stress echocardiography, cardiac computed tomography angiography [CCTA], and myocardial perfusion imaging [MPI] as well as no testing), among patients evaluated for chest pain. To compare costs among the tested (overall and by testing strategy) and nontested groups, we used a log-gamma generalized linear model to account for the skewed distribution of health care cost data, adjusting for relevant clinical covariates. A total of 2,340,699 patients were included in our cohort, of whom 481,170 (21%) patients received 1 of the 4 NITs. Among patients who received a NIT, 254,492 (53%) received a GXT as their initial test, 154,137 (32%) received MPI, 69,160 (14%) received a stress echo, and 3,381 (<1%) received a CCTA. After adjustment for differences in baseline patient characteristics, receipt of any NIT was associated with an approximate 12% reduction in downstream 1-year mean costs (cost ratio= 0.88; 95% CI, 0.87, 0.89) compared with those without any testing. Comparing the different testing strategies with no testing, both GXT (cost ratio= 0.80; 95% CI, 0.79-0.81) and stress echocardiography (cost ratio= 0.82; 95% CI, 0.81-0.83) were associated with the lower downstream costs, while both MPI (cost ratio= 1.26; 95% CI, 1.25, 1.27) and CCTA (cost ratio= 1.29; 95% CI, 1.23, 1.35) were associated with higher downstream costs. In a large population-based cohort consisting of >2 million people evaluated for chest pain, we report that receipt of noninvasive testing was associated with a 12% reduction in downstream costs when compared with no testing. Graded exercise stress testing and stress echocardiography were associated with the least downstream costs, whereas CCTA and MPI were associated with higher costs when compared with no testing. These findings may help inform testing decisions in chest pain patients.

Two- and three-dimensional indicators of green and grey space exposure and psychiatric conditions and medicine use: A longitudinal study in a large population-based Italian cohort

BackgroundEvidence available on the associations between urban greenness and mental health is mainly based on cross-sectional studies and has relied on 2D indicators of greenness. This longitudinal study aimed at investigating the association between 2D and 3D indicators of green and grey spaces and incident mental health-related outcomes in a large population-based cohort. MethodsOur study used data from 593,894 Italian adults (≥30 years) from the Rome Longitudinal Study. Mental health outcomes were defined using either drug prescriptions (antidepressants, antipsychotics, lithium and other mood stabilisers, and anxiolytics, hypnotics and sedatives), or hospitalisation records (for schizophrenia spectrum disorder, depression, anxiety, stress-related and somatoform, or substance use disorders). We obtained 2D and 3D indicators of green and grey exposures including Normalized Difference Vegetation Index (NDVI), green volume, grey volume, number of trees, and Normalized Difference Green-Grey Volume Index around participants’ homes. Cox proportional hazards regression models were developed to estimate the association of green and grey space exposure and psychiatric conditions and medicine use, adjusted for relevant covariates. ResultsWe found beneficial associations of NDVI and the number of trees with antipsychotic and lithium and other mood stabiliser drugs. We also observed detrimental associations between grey volume and lithium and other mood stabilisers and anxiolytic, hypnotic and sedative drugs. Finally, we found a protective association of the NDGG with lithium and other mood stabilisers (HR: 0.977; 95% CI: 0.965–0.990) and anxiolytic, hypnotic and sedative drugs (HR: 0.851; 95% CI: 0.762–0.950). The associations for hospitalisation for psychiatric conditions were less consistent and generally not statistically significant. ConclusionsFindings suggested that higher greenness areas around residential addresses are associated with reduced use of drugs for psychiatric conditions, while the opposite is true for higher grey space exposure. The study highlights the importance of accurately characterising green and grey spaces, using novel exposure indicators.

Characteristics and prognosis of patients with elevated triglycerides in acute myocardial infarction: observational data from a large database over a 17-year period: High triglycerides in acute myocardial infarction

From a large regional registry, we aimed to address the characteristics and prognosis of patients with elevated triglycerides (TG) among patients hospitalized for an acute myocardial infarction (MI). From the multicenter database of the RICO survey, all consecutive patients hospitalized for an acute MI (2001-2017) and alive at discharge were included. Among the 10,667 patients included, 17.7% had elevated TG. When compared with patients with TG ≤ 200 mg/dL, patients with high TG (>200 mg/dL) were 10 years younger, had a higher BMI, were more frequently men, diabetic, and smokers. At 1-year follow-up, recurrent ischemic events were more frequent in elevated TG patients. In multivariate logistic regression analysis, high TG (OR (95%CI): 1.356 (1.095-1.679)) remained an independent estimate for recurrent ischemic events, even after adjustment for confounding factors. In our large population-based cohort, elevated TG are common in acute MI, and associated with residual risk of recurrent ischemic events, beyond traditional prognostic markers.