Software application profile: tpc and micd-R packages for causal discovery with incomplete cohort data.

MOTIVATION: The Peter Clark (PC) algorithm is a popular causal discovery method to learn causal graphs in a data-driven way. Until recently, existing PC algorithm implementations in R had important limitations regarding missing values, temporal structure or mixed measurement scales (categorical/continuous), which are all common features of cohort data. The new R packages presented here, micd and tpc, fill these gaps. IMPLEMENTATION: micd and tpc packages are R packages. GENERAL FEATURES: The micd package provides add-on functionality for dealing with missing values to the existing pcalg R package, including methods for multiple imputations relying on the Missing At Random assumption. Also, micd allows for mixed measurement scales assuming conditional Gaussianity. The tpc package efficiently exploits temporal information in a way that results in a more informative output that is less prone to statistical errors. AVAILABILITY: The tpc and micd packages are freely available on the Comprehensive R Archive Network (CRAN). Their source code is also available on GitHub (https://github.com/bips-hb/micd; https://github.com/bips-hb/tpc).

Dose-response association between walking speed and all-cause mortality: A systematic review and meta-analysis of cohort studies.

This review aims to investigate the dose-response relationship between walking speed and all-cause mortality. PubMed, Web of Science, Embase and Cochrane Library were searched to September, 2023 for cohort studies. A meta-analysis estimated the overall hazard ratio (HR) of mortality incidence and 95% Confidence Interval (CI) for individuals with the fastest walking speed compared to those with the slowest walking speed. Subgroup analyses were conducted based on sex, age and speed-measuring methods. Dose-response meta-analyses were examined by using "mvmeta" packages available in STATA. A total of 13 studies involving 530,841 participants were included. Of these, 11 studies provided data for dose-response meta-analyses. Individuals in the fastest walking-speed category had a 43% lower risk of all-cause mortality compared to those in the slowest walking-speed category (HR = 0.57, 95% CI 0.48-0.66). There was an inverse linear dose-response relationship between walking speed and all-cause mortality; for every 0.1 m/s increment in walking speed, the risk of mortality decreased by 6% (HR = 0.94; 0.92-0.96). There was an inverse nonlinear dose-response relationship between them when participants' age was larger than 65 years, but linear dose-response relationships were detected in both the timed walking speed test and self-reported walking speed measurements.

Incidence and Risk Factors of Surgical Site Infection in Abdominal Surgeries: A Scoping Review of Cohort and Case-Control Studies.

Background: Abdominal surgery is considered a high-risk procedure for the development of surgical site infection (SSI). Few studies have evaluated the relative importance of surgical site infection risk factors in terms of consistency in abdominal surgery. Therefore, this comprehensive review article mapped and summarized the evidence aimed to determine the relative importance of the risk factors and incidence of SSIs in abdominal surgery. Methods: A literature review was conducted using electronic databases and search engines such as Scopus, PubMed, and Web of Science up to March 16, 2023. There was no language restriction for the papers to be included in the study. The relative consistency of the risk factors was measured and evaluated using the methodology of the Joanna Briggs Institute. Original peer-reviewed cohort and case-control studies were included if all types of SSIs were included. Meta-analysis was performed to determine the pooled estimates of SSI incidences. Results: Of 14,237 identified records, 107 articles were included in the review. The pooled incidence of SSI was 10.6% (95% CI: 9.02-12.55%, χ2=12986.44, P<0.001). Operative time and higher wound class were both significant consistent risk factors for SSI incidence. Patients' educational status, malnutrition, functional status, and history of neurological/psychiatric disorders were all candidates for consistent risk factors, with insufficient evidence. Conclusion: The findings of the present study indicated that SSI in abdominal surgery was a multifactorial phenomenon with a considerable risk and had different risk factors with various relative importance. Determining the relative importance of the risk factors for the prevention and control of SSI is strongly recommended.This manuscript has been released as a preprint at the research square: (https://doi.org/10.21203/rs.3.rs-3219597/v1).

Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS).

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

Persistent low-level viraemia is associated with non-infectious comorbidities in an observational cohort in four African countries.

INTRODUCTION: People living with HIV (PLWH) have higher rates of non-infectious comorbid diseases (NCDs) than individuals without HIV. We characterized the risk of NCDs among PLWH with undetectable viral load and persistent low-level viraemia (pLLV) in the African Cohort Study (AFRICOS). We secondarily quantified the role of immune activation in the association between LLV and NCDs. METHODS: AFRICOS enrols participants in 12 clinics in Uganda, Kenya, Tanzania and Nigeria. Participants on antiretroviral therapy ≥ 6 months without an NCD at enrolment were included. PLLV was defined as at least two consecutive visits with a detectable viral load <1000 copies/ml. We examined elevated blood pressure, hypercholesterolemia, hyperglycaemia, renal insufficiency and a composite variable of any NCD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard modelling. Among a subset of participants with biomarker data, we assessed the interaction between viral load and 13 biomarkers in the association with any NCD. RESULTS: From 23 January 2013 to 1 December 2022, 1755 participants met the inclusion criteria for these analyses. At the first eligible visit, the majority of participants had an undetectable viral load (n = 1375, 78.35%). Participants with pLLV had an increased rate of developing any NCD (aHR: 1.22, 95% CI: 1.02-1.47) compared to participants with an undetectable viral load. There was a statistically significant interaction between LLV and TNF-α, CCL2/MCP-1 and TNF-RII in the association with any NCD. CONCLUSIONS: PLLV was significantly associated with NCDs and immune inflammation in this population. Aggressive management of LLV may positively impact NCDs in PLWH.

Relative contribution of comorbid diseases to health-related quality of life in patients with Parkinson's disease.

BACKGROUND: Multimorbidity is common in elderly people, and one of the major consequences of multimorbidity is low health-related quality of life (HRQoL). The aim of this study was to investigate the frequency of comorbid diseases in patients with Parkinson's disease (PD) and to analyze their relative importance in HRQoL. The aim was also to examine agreement between the generic 15D questionnaire and the PD-specific Parkinson's Disease Questionnaire (PDQ-8) to further validate 15D in the evaluation of HRQoL in patients with PD. METHODS: Patients with PD (N = 551) filled a questionnaire on comorbid diseases, and the 15D questionnaire yielding a 15-dimensional health profile and a score representing the overall HRQoL. Self-organizing map was used for an unsupervised pattern recognition of the health profiles. Relative importance analysis was used to evaluate the contribution of 16 comorbid diseases to the 15D score. The agreement between 15D and PDQ-8 questionnaires was studied in a subset of 81 patients that were examined clinically. RESULTS: 533 patients (96.7%) reported comorbid diseases. The most affected dimensions in the 15D questionnaire were secretion, usual activities, discomfort and symptoms, and sexual activity. Self-organizing map identified three patterns of health profiles that included patients with high, low or transition HRQoL. The transition subgroup was similar to low HRQoL subgroup in non-motor dimensions. Sixteen comorbid diseases explained 33.7% of the variance in the 15D score. Memory deficit, depression, heart failure, and atrial fibrillation had the highest relative importance. The intraclass correlation coefficient between the generic 15D and the PD-specific PDQ-8 was 0.642 suggesting moderate reliability. CONCLUSIONS: The most marked differences in HRQoL were in the dimensions of secretion, usual activities, and sexual activity. Pattern detection of 15D health dimensions enabled the detection of a subgroup with disproportionately poor HRQoL in non-motor dimensions. The comorbid diseases affecting most to HRQoL were memory deficit and depression. The generic 15D questionnaire can be used in the evaluation of HRQoL in PD patients.

Very Long-term Risk of Moderate-Severe Post-Thrombotic Syndrome after Deep Vein Thrombosis.

BACKGROUND: Post thrombotic syndrome (PTS) refers to manifestations of chronic venous insufficiency (CVI) after a deep vein thrombosis (DVT). The risk of developing moderate-severe PTS in the very long-term is largely unknown and particularly in case of distal DVT. Furthermore, the impact of DVT vs. other causes of CVI on long-term manifestations of PTS is also unknown. OBJECTIVES: To assess the very long-term risk of moderate-severe PTS after DVT and the role that DVT plays in PTS symptoms. PATIENTS/METHODS: Patients with lower limb DVT enrolled in the multicenter OPTIMEV study underwent a very long-term telephone follow-up. We assessed: i) the proportion of moderatesevere PTS (assessed with the patient-reported Villalta score) according to DVT extent and, ii) the population attributable fraction (PAF) that DVT plays in patients moderate-severe PTS manifestations. RESULTS: 14 years after DVT, moderate-severe PTS developed in 35 of 185 patients with distal DVT (18.9%[95%CI: 13.5% ; 25.3%], 11 of 47 patients with popliteal DVT (23.4%[12.3% ; 38.0%]) and 27 of 74 patients with ilio-femoral DVT (36.5%[25.6% ; 48.5%]). The PAF of DVT in moderate-severe symptoms of PTS, was respectively, 25.7%[-18.1% ; 53.3%] in patients with distal DVT, 27.3%[-63.7% ; 67.7%] in patients with popliteal DVT and 43.1%[+0.7% ; 67.4%] in patients with ilio-femoral DVT. CONCLUSION: In the very long-term after DVT, a quarter of patients have moderate-severe PTS manifestations. However, the impact of the DVT on these manifestations appears nonpredominant and varies according to DVT extent. Distal DVT does not significantly increase the risk of developing moderate-severe PTS.

Subsequent musculoskeletal injury after concussion in National Football League players.

OBJECTIVE: To assess whether National Football League (NFL) players diagnosed with a concussion have an increased risk of injury after return to football. METHODS: A retrospective cohort study analysed the hazard of subsequent time-loss lower extremity (LEX) or any musculoskeletal injury among NFL players diagnosed with a concussion in 2015-2021 preseason or regular season games compared with: (1) all non-concussed players participating in the same game and (2) players with time-loss upper extremity injury. Cox proportional hazards models were adjusted for number of injuries and concussions in the prior year, player tenure and roster position. Additional models accounted for time lost from participation after concussion. RESULTS: There was no statistical difference in the hazards of LEX injury or any musculoskeletal injury among concussed players compared with non-concussed players, though concussed players had a slightly elevated hazard of injury (LEX injury: HR=1.12, 95% CI 0.90 to 1.41; any musculoskeletal injury: HR=1.08, 95% CI: 0.89 to 1.31). When comparing to players with upper extremity injuries, the hazard of injury for concussed players was not statistically different, though HRs suggested a lower injury risk among concussed players (LEX injury: HR=0.78, 95% CI: 0.60 to 1.02; any musculoskeletal injury: HR=0.82, 95% CI: 0.65 to 1.04). CONCLUSION: We found no statistical difference in the risk of subsequent injury among NFL players returning from concussion compared with non-concussed players in the same game or players returning from upper extremity injury. These results suggest deconditioning or other factors associated with lost participation time may explain subsequent injury risk in concussed players observed in some settings after return to play.

Prenatal and early-life air pollutant exposure and epigenetic aging acceleration.

BACKGROUND: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. RESULTS: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 µg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM2.5 (4.76 µg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM10 (4.30 µg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively. CONCLUSION: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.

The impact of comorbidity burden on cardiac arrest mortality: A population-based cohort study.

AIM: Patients experiencing cardiac arrest are often burdened with comorbidities that increase mortality. This study examined the impact of comorbidity burden on cardiac arrest mortality by quantifying biological interaction. METHODS: Nationwide population-based Danish cohort study of adult patients hospitalized for cardiac arrest during 1996-2021 and 5:1 matched comparisons from the general population (matched on age, sex, calendar year, and all Charlson Comorbidity Index comorbidities). Mortality rates and hazard ratios for the association between cardiac arrest and mortality was calculated according to comorbidity burden (none, low, moderate, severe). Biological interaction was examined by calculating interaction contrasts (difference in rate differences). RESULTS: For no comorbidity burden, the 30-day mortality rate per 1,000 person-years was 18,110 in the cardiac arrest cohort and 24 in the comparison cohort (hazard ratio = 1,435). For low comorbidity burden, the 30-day mortality rate increased to 20,272 in the cardiac arrest cohort and 41 in the comparison cohort (hazard ratio = 504). The corresponding interaction contrast of 2,145 indicated that 11% of the mortality rate in patients with cardiac arrest and low comorbidity burden was explained by interaction between the two. This percentage increased to 20% for moderate and to 28% for severe comorbidity burden. Within 31-365-day follow-up, the percentage of the mortality rate explained by interaction was 28% for low, 38% for moderate, and 41% for severe comorbidity burden. The interaction effect was present for both out-of-hospital and in-hospital cardiac arrest. CONCLUSIONS: Comorbidity burden interacted with cardiac arrest to increase mortality beyond that explained by their separate effects.

Association of Uterine Leiomyoma with Type 2 Diabetes Mellitus in Young Women: A Population-Based Cohort Study.

Background: We investigated the association between uterine leiomyoma (UL) and incident type 2 diabetes mellitus (T2DM) in young women. Methods: A nationwide population-based cohort study of 2,541,550 women aged between 20 and 40 years was performed using the National Health Information Database. Cox proportional hazards models were used to analyze the risk of incident T2DM according to the presence of UL and myomectomy. Results: The mean age was 29.70 years, and mean body mass index was 21.31 kg/m2. Among 2,541,550 participants, 18,375 (0.72%) women had UL. During a median 7.45 years of follow-up, 23,829 women (0.94%) were diagnosed with T2DM. The incidence of T2DM in women with UL (1.805/1,000 person-years) was higher than in those without UL (1.289/1,000 person-years). Compared with women without UL, women with UL had a higher risk of incident T2DM (hazard ratio, 1.216; 95% confidence interval [CI], 1.071 to 1.382). Women with UL who did not undergo myomectomy had a 1.505 times (95% CI, 1.297 to 1.748) higher risk for incident T2DM than women without UL. However, women with UL who underwent myomectomy did not have increased risk for incident T2DM. Conclusion: Young women with UL were associated with a high risk of incident T2DM. In addition, myomectomy seemed to attenuate the risk for incident T2DM in young women with UL.

Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey.

BACKGROUND: In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. METHODS: We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. RESULTS: Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. CONCLUSIONS: Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

Bidirectional association between type 2 diabetes and irritable bowel syndrome: A large-scale prospective cohort study.

AIM: To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort. METHODS: Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs). RESULTS: In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings. CONCLUSIONS: T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases.

Diagnostic and demographic factors of pediatric and adult catatonia hospitalizations: A 2016-2020 National Inpatient Sample Study.

OBJECTIVE: Catatonia is a neuropsychiatric disorder that can occur in patients of any age, but it is uncertain whether patient demographics or underlying diagnoses differ between pediatric and adult patients. This study investigates patients of all ages diagnosed with catatonia during acute care hospitalizations in the United States over a 5-year period. METHOD: The National Inpatient Sample, an all-payors database of acute care hospital discharges, was queried for patients with a discharge diagnosis of catatonia between 2016 and 2020 with patients stratified by age as pediatric (≤18 years) or adult (>18 years). RESULTS: Among 174,776,205 hospitalizations recorded in the NIS from 2016 to 2020, 61,990 (95% CI: 60,257 to 63,723; 0.035%) involved a diagnosis of catatonia. Of these, 3255 were for pediatric patients and 58,735 were for adult patients. Compared with adult patients, pediatric catatonia patients were more likely to be male and non-White. Diagnostically, psychotic disorders, encephalitis, and neurodevelopmental disorders were more common primary discharge diagnoses in pediatric patients, while adult patients more frequently were diagnosed with mood disorders. Length of stay was not significantly different between pediatric and adult catatonia hospitalizations. Physical restraints were commonly applied for patients with catatonia. CONCLUSION: Pediatric and adult catatonia patients differed in sex, race, and diagnosis, although hospital length of stay was not different between pediatric and adult catatonia hospitalizations. These results may inform catatonia diagnosis in the hospital setting and point to disparities that could be targets of quality improvement efforts.

Comparison of Asthma Phenotypes in Severe Asthma Cohorts (SARP, U-BIOPRED, ProAR and COREA) From 4 Continents.

PURPOSE: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. METHODS: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. RESULTS: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. CONCLUSIONS: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.

Mixed effects models but not t-tests or linear regression detect progression of apathy in Parkinson's disease over seven years in a cohort: a comparative analysis.

INTRODUCTION: While there is an interest in defining longitudinal change in people with chronic illness like Parkinson's disease (PD), statistical analysis of longitudinal data is not straightforward for clinical researchers. Here, we aim to demonstrate how the choice of statistical method may influence research outcomes, (e.g., progression in apathy), specifically the size of longitudinal effect estimates, in a cohort. METHODS: In this retrospective longitudinal analysis of 802 people with typical Parkinson's disease in the Luxembourg Parkinson's study, we compared the mean apathy scores at visit 1 and visit 8 by means of the paired two-sided t-test. Additionally, we analysed the relationship between the visit numbers and the apathy score using linear regression and longitudinal two-level mixed effects models. RESULTS: Mixed effects models were the only method able to detect progression of apathy over time. While the effects estimated for the group comparison and the linear regression were smaller with high p-values (+ 1.016/ 7 years, p = 0.107, -0.056/ 7 years, p = 0.897, respectively), effect estimates for the mixed effects models were positive with a very small p-value, indicating a significant increase in apathy symptoms by + 2.345/ 7 years (p < 0.001). CONCLUSION: The inappropriate use of paired t-tests and linear regression to analyse longitudinal data can lead to underpowered analyses and an underestimation of longitudinal change. While mixed effects models are not without limitations and need to be altered to model the time sequence between the exposure and the outcome, they are worth considering for longitudinal data analyses. In case this is not possible, limitations of the analytical approach need to be discussed and taken into account in the interpretation.

Derivation and external validation of a portable method to identify patients with pulmonary embolism from radiology reports: The READ-PE algorithm.

BACKGROUND: Identification of pulmonary embolism (PE) across a cohort currently requires burdensome manual review. Previous approaches to automate capture of PE diagnosis have either been too complex for widespread use or have lacked external validation. We sought to develop and validate the Regular Expression Aided Determination of PE (READ-PE) algorithm, which uses a portable text-matching approach to identify PE in reports from computed tomography with angiography (CTA). METHODS: We identified derivation and validation cohorts of final radiology reports for CTAs obtained on adults (≥ 18 years) at two independent, quaternary academic emergency departments (EDs) in the United States. All reports were in the English language. We manually reviewed CTA reports for PE as a reference standard. In the derivation cohort, we developed the READ-PE algorithm by iteratively combining regular expressions to identify PE. We validated the READ-PE algorithm in an independent cohort, and compared performance against three prior algorithms with sensitivity, specificity, positive-predictive-value (PPV), negative-predictive-value (NPV), and the F1 score. RESULTS: Among 2948 CTAs in the derivation cohort 10.8 % had PE and the READ-PE algorithm reached 93 % sensitivity, 99 % specificity, 94 % PPV, 99 % NPV, and 0.93 F1 score, compared to F1 scores ranging from 0.50 to 0.85 for three prior algorithms. Among 1206 CTAs in the validation cohort 9.2 % had PE and the algorithm had 98 % sensitivity, 98 % specificity, 85 % PPV, 100 % NPV, and 0.91 F1 score. CONCLUSIONS: The externally validated READ-PE algorithm identifies PE in English-language reports from CTAs obtained in the ED with high accuracy. This algorithm may be used in the electronic health record to accurately identify PE for research or surveillance. If implemented at other EDs, it should first undergo local validation and may require maintenance over time.

Association between internet exclusion and depressive symptoms among older adults: panel data analysis of five longitudinal cohort studies.

Background: Internet exclusion and depressive symptoms are prevalent phenomena among older adults; however, the association between internet exclusion and depressive symptoms remains limited. This study aims to investigate the association between internet exclusion and depressive symptoms among older adults from high-income countries (HICs) and low- and middle-income countries (LMICs). Methods: We conducted a comprehensive longitudinal, cross-cultural analysis, and the participants were adults aged 60 years and older from 32 countries participating in five nationally representative longitudinal cohort studies: the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), the China Health and Retirement Longitudinal Study (CHARLS), and the Mexican Health and Ageing Study (MHAS). Internet exclusion was defined as the self-reported absence from internet use. Depressive symptoms were evaluated using the Centre for Epidemiologic Studies of Depression scale (CES-D) or the Euro-Depression scale (Euro-D). These five cohorts, being heterogeneous, were respectively conducted with panel data analysis. Logistic regression, implemented within the generalized estimating equations framework, was used to examine the association between internet exclusion and the likelihood of experiencing depressive symptoms, adjusting for the causal-directed-acyclic-graph (DAG) minimal sufficient adjustment set (MSAS), including gender, age, education, labour force status, household wealth level, marital status, co-residence with children, residence status, cognitive impairment, and functional ability. Findings: Our study included a total of 129,847 older adults during the period from 2010 to 2020, with a median follow-up of 5 (2, 7) years. The pooled proportion of internet exclusion was 46.0% in HRS, 32.6% in ELSA, 54.8% in SHARE, 92.3% in CHARLS, and 65.3% in MHAS. Internet exclusion was significantly associated with depressive symptoms across all cohort studies: HRS (OR = 1.13, 95% CI 1.07-1.20), ELSA (OR = 1.22, 95% CI 1.11-1.34), SHARE (OR = 1.55, 95% CI 1.47-1.62), CHARLS (OR = 1.49, 95% CI 1.26-1.77), and MHAS (OR = 1.48, 95% CI 1.39-1.58). Moreover, internet exclusion was found to be associated with all dimensions of depression in the SHARE, MHAS, and ELSA cohorts (except for sleep and felt sad) cohorts. Interpretation: A considerable proportion of older adults experienced internet exclusion, particularly those in LMICs. Internet exclusion among older adults, irrespective of their geographic location in HICs or LMICs, was associated with a higher likelihood of experiencing depressive symptoms, which demonstrated the importance of addressing barriers to internet access and promoting active participation in the internet society among older adults. Funding: National Key R&D Program of China (grant number 2022ZD0160704), the Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University (grant number ZYCXTD2023005), the Collaborative Innovation Major Project of Zhengzhou (grant number 20XTZX08017), the Joint Project of Medical Science and Technology of Henan Province (grant number LHGJ20220428), and National Natural Science Foundation of China (grant number 82373341).

Emulating Randomized Trials by Observational Database Studies: The RCT-DUPLICATE Initiative in COPD and Asthma.

Observational studies are increasingly used to provide real-world evidence in regulatory decision-making. The RCT-DUPLICATE initiative conducted observational studies emulating two trials in patients with asthma and three in COPD. For each trial, new-user cohorts were constructed from two US healthcare claims databases, comparing initiators of the study and comparator drugs, matched on propensity scores. Proportional hazards models were used to compare the treatments on study outcomes. The observational studies involved more subjects than the corresponding trials, with treatment arms well-matched on baseline characteristics. An asthma example involved emulation of the 26-week FDA-mandated D5896 trial. With 6,494 asthma patients per arm, the hazard ratio (HR) of a serious asthma-related event with budesonide-formoterol versus budesonide was 1.29 (95% CI: 0.63-2.65), compared with 1.07 (95% CI: 0.70-1.65) in the trial. A COPD example is the emulation of the one-year IMPACT trial. With 4,365 COPD patients per arm, the HR of a COPD exacerbation with triple therapy versus dual bronchodilators was 1.08 (95% CI: 1.00-1.17), compared with 0.84 (95% CI: 0.78-0.91) in the trial. We found mainly discordant results between observational analyses and randomized trials, likely from the forced discontinuation of treatments prior to randomization in the trials, not mimicable in the observational analyses.