Unmeasured Risk Factors Research Articles

Efficient Risk Assessment of Time-to-Event Targets With Adaptive Information Transfer.

Using informative sources to enhance statistical analysis in target studies has become an increasingly popular research topic. However, cohorts with time-to-event outcomes have not received sufficient attention, and external studies often encounter issues of incomparability due to population heterogeneity and unmeasured risk factors. To improve individualized risk assessments, we propose a novel methodology that adaptively borrows information from multiple incomparable sources. By extracting aggregate statistics through transitional models applied to both the external sources and the target population, we incorporate this information efficiently using the control variate technique. This approach eliminates the need to load individual-level records from sources directly, resulting in low computational complexity and strong privacy protection. Asymptotically, our estimators of both relative and baseline risks are more efficient than traditional results, and the power of covariate effects testing is much enhanced. We demonstrate the practical performance of our method via extensive simulations and a real case study.

Effect of Early Levodopa Treatment on Mortality in People with Parkinson's Disease.

The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long-term effects of levodopa. The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries. Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as "early initiators" (initiating levodopa within 2 years of diagnosis) or "nonearly initiators." We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates. Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05). Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.

Incorporating Road Network Connectivity in Neighboring Structures for Crash Prediction Models at the Area Level

Spatial correlation models have been traditionally used in road safety to account for spatial effects resulting from unmeasured or unknown risk factors that induce spatial correlation between neighboring areas. In transportation, the interaction between neighboring areas is highly influenced by the number of roads that connect those areas and the importance of those roads. This paper proposes an approach in which the weights of the spatial interaction (and therefore the spatial correlation) between areas depends on the number of road connections between those areas and the importance of those connections. The results using districts in Costa Rica show that the inclusion of road network connectivity in the models of spatial correlation significantly improves model fit, even after accounting for model complexity using the deviance information criterion (DIC) and widely applicable information criterion (WAIC). The inclusion of higher weights for national roads compared to municipal or local roads further improved the model fit. The best three models with respect to the posterior deviance, DIC, and WAIC are those that give at least three times more weight to national roads compared to local roads. With respect to site ranking, those three models present similar results, which also highlights the consistency among those models.

Abstract 15409: Analysis of Discrimination and Calibration of Two Cardiovascular Risk Scores in Patients With Non-Alcoholic Steatohepatitis Shows a Need for Improved Accuracy of These Models

Background: CV risk can be estimated by risk scores such as the Framingham and the Pooled Cohort Equations (PCE). The applicability of these tools in present day NASH (non-alcoholic steatohepatitis) cohorts, individuals with increased morbidity and mortality from CVD, was evaluated to assess their relevance. Hypothesis: The Null Hypothesis is that there is no difference between the predicted CV risk as estimated by the Framingham or PCE risk scores, and the actual CV events that occur in a NAFLD (non-alcoholic fatty liver disease)/ NASH cohort. Aim: To assess the prognostic performance of the Framingham and PCE risk scores in a NAFLD/NASH cohort. Methods: The study population were US patients in the observational TARGET-NASH study with NAFLD/NASH aged 18 years or older. Patients with any CV history at or prior to index were excluded. Patients’ five-year CV risk was estimated using recalibrated Framingham and PCE models and compared with observed CV events. Model discrimination and calibration were assessed using the area under the receiver operator curve (AUROC) and Hosmer-Lemeshow test statistic, respectively. Results: 980 and 587 patients in the Framingham and PCE cohorts, respectively, had all data needed for calculation of CV risk, of which 274 and 169 had at least five years of follow-up. Framingham five-year predicted CV risk was significantly greater among patients who did vs did not experience a CV event (13.7% [SD 9.0] vs 10.5% [SD 8.8]; p=0.02). No statistically significant difference was observed in the PCE analysis. The AUROC was 0.62 (95% CI 0.51, 0.73) for Framingham and 0.58 (95% CI 0.44, 0.72) for PCE at five years, with worst predictive performance among the subgroup of cirrhotic NASH patients for both risk equations. Analyses of model calibration revealed a statistically significant lack of calibration for both tools at five years (Framingham: χ 2 =25.58, p=0.001; PCE: χ 2 =33.86, p<0.001). Conclusion: Framingham and PCE may have poor predictive accuracy for CVD risk in NAFLD/NASH cohorts. This tended to be most apparent among the upper decile of predicted risk, with predicted values far exceeding the observed. Lack of ten-year follow-up and unmeasured risk factors may also explain some of the residual overestimation not accounted for in our models.

Invited Commentary: Beyond Barker-Mothers Are the Ones at Risk.

Dr. David Barker hypothesized that low birth weight (LBW) is the result of inadequate fetal nutrition, leading to increased risk ofcardiovascular disease (CVD) in the offspring. This hypothesis has stimulated thousands of reports on low birth weight (LBW) and CVD risk. One problem with this association is that many LBW infants are small because they are preterm, not growth-restricted. A second problem is that maternal CVD risk factors confound the association. In an accompanying article, Lu et al. (Am J Epidemiol. 2023;192(6):866-877) address both concerns. Using population data from Sweden and Denmark, the authors estimated CVD incidence among offspring born small for gestational age (SGA). The smallest 3% had a CVD hazard ratio of 1.44 (95% confidence interval: 1.38, 1.51). Even this moderate risk mostly evaporated in sibship analysis, which controlled for unmeasured maternal CVD risk factors (hazard ratio = 1.11, 95% confidence interval: 0.99, 1.25). The risk highlighted by Barker is negligible, especially when compared with a more urgent health issue-cardiovascular risk in women with pregnancy complications. Mothers of SGA infants have up to a 3-fold CVD risk, and mothers with preeclampsia and preterm delivery have up to a 9-fold risk. Pregnancy complications thus provide an early marker of a woman's propensity to develop CVD, and perhaps an opportunity for early intervention. From a public health perspective, Barker's hypothesis about CVD risk in LBW offspring is less compelling than the question of CVD risk among mothers with pregnancy complications. This article is part of a Special Collection on ABC.

Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden.

Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD. Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD.

Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.

Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).

Prenatal alcohol exposure and child sleep problems: Afamily-based quasi-experimental study.

We examine whether associations between prenatal exposure to hazardous maternal alcohol consumption during the first trimester of pregnancy and sleep problems in young children represent a causal association. The population-based sample consists of 15,911 mothers with 30,395 offspring from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). Women self-reported pre-pregnancy alcohol consumption and consumption during the first trimester of pregnancy twice: at gestational weeks 17 and 30. Mothers reported their children's sleep problems, when they were 1.5 and 3years (mean=50; SD=10). We tested models adjusting for (1) measured confounders, (2) unmeasured familial risk factors by sibling design, and (3) maternal hazardous drinking in the 3months prior to pregnancy as an instrumental variable within the sibling design. Children of mothers with hazardous drinking during the first trimester were at increased risk of sleep problems at 1.5 (β=1.14, 95%CI 0.04-2.25) and 3 (β=2.86, 95%CI 1.85-3.87) years of age. These associations were reduced to close to zero and non-significant at 1.5 (β=-0.32, 95%CI -1.91-1.26) and 3 (β=0.06, 95%CI -1.56-1.64) years when controlling for both familial and measured environmental risk factors. There is a moderate association between maternal hazardous drinking during pregnancy and offspring sleep problems up to age three. This association is explained by risk factors differing between families and does not reflect a cause-effect relationship.

Preterm birth, abnormal foetal growth and the risk of atrial fibrillation later in life: a cohort study in Denmark, Finland and Sweden

Abstract Background Increasing evidence suggests that adverse birth outcomes, including preterm birth, small for gestational age (SGA) and large for gestational age (LGA), are associated with increased risks of hypertension, ischemic heart disease, stroke and heart failure. However, knowledge regarding their associations with atrial fibrillation (AF) is limited and inconsistent. Objective To investigate whether preterm birth, SGA and LGA are associated with increased risks of AF later in life. Methods We conducted a population-based cohort study involving 8,012,433 live singleton births based on the nation-wide Danish (1978–2016), Swedish (1973–2014) and Finnish (1987–2014) Medical Birth Registers. Information on birth outcomes, atrial fibrillation and covariates was obtained from nationwide health and socioeconomic registers. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for AF according to preterm birth (<37 weeks), SGA and LGA (<10th and >90th birth weight for gestational age percentiles, respectively) with multivariable Cox proportional hazard models and flexible parametric survival models. We conducted sibling analyses to control for unmeasured familial risk factors. Results Preterm birth and LGA were associated with increased AF risks in both the full population cohort and in the sibling analyses; the multivariate HRs (95% CI) from the cohort analyses were 1.53 (1.37–1.71) and 1.55 (1.44–1.65), respectively. The associations were stronger with AF in childhood than in adulthood. Children born SGA had an increased risk of AF in the first 18 years of life, but not later. Conclusions Individuals born preterm or LGA had an increased AF risk independently of familial confounding factors. Individuals born SGA had an increased AF risk only during childhood. Persons born prematurely or with abnormal foetal growth may benefit from early screening and prevention to reduce the risk of AF later in life. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Council for Working Life and Social Research; China Scholarship Council

Implications of Mortality Displacement for Effect Modification and Selection Bias

Mortality displacement is the concept that deaths are moved forward in time (e.g., a few days, several months, and years) by exposure from when they would occur without the exposure, which is common in environmental time-series studies. Using concepts of a frail population and loss of life expectancy, it is understood that mortality displacement may decrease rate ratio (RR). Such decreases are thought to be minimal or substantial depending on study populations. Environmental epidemiologists have interpreted RR considering mortality displacement. This theoretical paper reveals that mortality displacement can be formulated as a built-in selection bias of RR in Cox models due to unmeasured risk factors independent from exposure of interest, and mortality displacement can also be viewed as an effect modifier by integrating the concepts of rate and loss of life expectancy. Thus, depending on the framework through which we view bias, mortality displacement can be categorized as selection bias in the bias taxonomy of epidemiology, and simultaneously mortality displacement can be seen as an effect modifier. This dichotomy provides useful implications regarding policy, effect modification, exposure time-windows selection, and generalizability, specifically why research in epidemiology may produce unexpected and heterogeneous RR over different studies and sub-populations. Keywords: Selection bias, Effect modification, Mediation, Directed Acyclic Graph, Frailty, Depletion of susceptible, Non-collapsibility, Generalizability, Hazard ratio (HR), Rate Ratio (RR),

Hospital-treated infections in early- and mid-life and risk of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis: A nationwide nested case-control study in Sweden.

Experimental observations have suggested a role of infection in the etiology of neurodegenerative disease. In human studies, however, it is difficult to disentangle whether infection is a risk factor or rather a comorbidity or secondary event of neurodegenerative disease. To this end, we examined the risk of 3 most common neurodegenerative diseases in relation to previous inpatient or outpatient episodes of hospital-treated infections. We performed a nested case-control study based on several national registers in Sweden. Cases were individuals newly diagnosed with Alzheimer's disease (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) during 1970 to 2016 in Sweden, identified from the National Patient Register. For each case, 5 controls individually matched to the case on sex and year of birth were randomly selected from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for potential confounders, including sex, year of birth, area of residence, educational attainment, family history of neurodegenerative disease, and Charlson comorbidity index. Infections experienced within 5 years before diagnosis of neurodegenerative disease were excluded to reduce the influence of surveillance bias and reverse causation. The analysis included 291,941 AD cases (median age at diagnosis: 76.2 years; male: 46.6%), 103,919 PD cases (74.3; 55.1%), and 10,161 ALS cases (69.3; 56.8%). A hospital-treated infection 5 or more years earlier was associated with an increased risk of AD (OR = 1.16, 95% CI: 1.15 to 1.18, P < 0.001) and PD (OR = 1.04, 95% CI: 1.02 to 1.06, P < 0.001). Similar results were observed for bacterial, viral, and other infections and among different sites of infection including gastrointestinal and genitourinary infections. Multiple infections before age 40 conveyed the greatest risk of AD (OR = 2.62, 95% CI: 2.52 to 2.72, P < 0.001) and PD (OR = 1.41, 95% CI: 1.29 to 1.53, P < 0.001). The associations were primarily due to AD and PD diagnosed before 60 years (OR = 1.93, 95% CI: 1.89 to 1.98 for AD, P < 0.001; OR = 1.29, 95% CI: 1.22 to 1.36 for PD, P < 0.001), whereas no association was found for those diagnosed at 60 years or older (OR = 1.00, 95% CI: 0.98 to 1.01 for AD, P = 0.508; OR = 1.01, 95% CI: 0.99 to 1.03 for PD, P = 0.382). No association was observed for ALS (OR = 0.97, 95% CI: 0.92 to 1.03, P = 0.384), regardless of age at diagnosis. Excluding infections experienced within 10 years before diagnosis of neurodegenerative disease confirmed these findings. Study limitations include the potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of the National Patient Register, as well as the residual confounding from unmeasured risk or protective factors for neurodegenerative diseases. Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of AD and PD, primarily among AD and PD cases diagnosed before 60 years. These findings suggest that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age. However, due to the observational nature of the study, these results do not formally prove a causal link.

Assessing seasonality and the role of its potential drivers in environmental epidemiology: a tutorial.

Several methods have been used to assess the seasonality of health outcomes in epidemiological studies. However, little information is available on the methods to study the changes in seasonality before and after adjusting for environmental or other known seasonally varying factors. Such investigations will help us understand the role of these factors in seasonal variation in health outcomes and further identify currently unknown or unmeasured risk factors. This tutorial illustrates a statistical procedure for examining the seasonality of health outcomes and their changes, after adjusting for potential environmental drivers by assessing and comparing shape, timings and size. We recommend a three-step procedure, each carried out and compared before and after adjustment: (i) inspecting the fitted seasonal curve to determine the broad shape of seasonality; (ii) identifying the peak and trough of seasonality to determine the timings of seasonality; and (iii) estimating the peak-to-trough ratio and attributable fraction to measure the size of seasonality. Reporting changes in these features on adjusting for potential drivers allows readers to understand their role in seasonality and the nature of any residual seasonal pattern. Furthermore, the proposed approach can be extended to other health outcomes and environmental drivers.

Risks of mental disorders among intensive care unit survivors: A nationwide cohort study in Taiwan

ObjectiveThis study aimed to investigate the risk of mental disorders among the intensive care unit (ICU) survivors compared with the hospitalized non-ICU and non-hospitalized patients. MethodWe extracted data from the Taiwanese National Health Insurance Research Database (NHIRD) to conduct a retrospective cohort study. Multivariate Cox proportional hazard regression models were used to analyze the data. Identified from the NHIRD, we matched 15,918 patients with ICU admissions, 63,672 patients without any inpatient admission (non-inpatient department [non-IPD] cohort), and 63,672 patients admitted to a general ward but not the ICU (non-ICU cohort). The patient records were extracted between the periods of 2000–2015 to identify any occurrence of mental disorders. ResultsDuring the study period, the overall risk of mental disorder diagnosis was 1.68-fold higher in the ICU cohort than the non-IPD cohort (95% confidence interval (CI): 1.23–1.89, P < 0.001). Alternatively, there were no differences in risks for any mental disorders between the ICU and non-ICU cohorts. ConclusionBoth admissions to the ICU and the general ward cohorts were associated with a higher risk of any mental disorders compared to the general population. Further clinical studies are warranted to confirm this association due to residual or unmeasured risk factors.

Drug exposure misclassification in pharmacoepidemiology: Sources and relative impact.

BackgroundDrug exposure assessment based on dispensing data can be misclassified when patients do not adhere to their therapy or when information about over‐the‐counter drugs is not captured in the study database. Previous research has considered hypothetical sensitivity and specificity values, whereas this study aims to assess the impact of literature‐based real values of exposure misclassification.MethodsA synthetic cohort study was constructed based on the proportion of exposure theoretically captured in a database (range 0.5–1.0) and the level of adherence (0.5–1.0). Three scenarios were explored: nondifferential misclassification, differential misclassification (misclassifications dependent on an unmeasured risk factor doubling the outcome risk), and nondifferential misclassification in a comparative effectiveness study (RRA and RRB both 2.0 compared to nonuse, RRA‐B 1.0).ResultsFor the scenarios with nondifferential misclassification, 25% nonadherence or 25% uncaptured exposure changed the RR from 2.0 to 1.75, and 1.95, respectively. Applying different proportions of nonadherence or uncaptured use (20% vs. 40%) for subgroups with and without the risk factor, an RR of 0.95 was observed in the absence of a true effect (i.e., true RR = 1). In the comparative effectiveness study, no effect on RR was seen for different proportions of uncaptured exposure; however, different levels of nonadherence for the drugs (20% vs. 40%) led to an underestimation of RRA‐B (0.89).DiscussionAll scenarios led to biased estimates, but the magnitude of the bias differed across scenarios. When testing the robustness of findings of pharmacoepidemiologic studies, we recommend using realistic values of nonadherence and uncaptured exposure based on real‐world data.

Changes in children's lung function over two decades in relation to socioeconomic, parental and household factors in Wuhan, China.

BackgroundIt is important to identify risk and beneficial factors for children’s lung function. This study aims to ascertain potential changes in children’s lung function in relation to changes in socioeconomic, parental and household factors, based on a comparison between two periods spanning 25 years in Wuhan, the largest metropolis in central China.MethodsIn two cross-sectional studies, lung function measurements and questionnaire surveys were conducted on school-age children in 1993–1996 (Period I) and in 2018 (Period II). Children of 6–12 years old from elementary schools were selected by a multistage sampling method. Demographic information, socioeconomic status, feeding methods, parental illness and behavior patterns, as well as household characteristics, were collected through a questionnaire survey. Spirometric lung function was measured, including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), forced expiratory flow at 25% and 75% of the pulmonary volume (FEF25–75), and peak expiratory flow (PEF). Wilcoxon analysis of variances was used to assess the differences in lung function indexes between Period I and Period II. Multiple linear regression models were used to estimate the association of lung function with regard to socioeconomic, parental and household factors, respectively.ResultsSignificant prevalence reductions were observed for household coal use, paternal smoking and maternal asthma, while the prevalence increased significantly for children sleeping in their own rooms or own beds and breastfeeding, ventilation use during cooking, and parental education level from Period I to Period II. When adjusted for age, height, weight, sex and other factors assessed in the study, children had significant lower values of FVC, FEV1, and PEF in Period II than in Period I. Enclosed kitchen was significantly associated with lower lung function in children in Period I. Urban living condition and higher maternal education level were each associated with a higher FVC, while father having no fixed income was associated with a lower FVC and a lower FEV1, respectively, in Period II. In comparison with Period I, the beneficial impact of urban living and that of breastfeeding were enhanced and the detrimental effect of poor household condition was weakened in Period II.ConclusionsLung function was lower in 2018 than in 1993–1996 in school-age children living in Wuhan. Although improvements in urban living and household environmental conditions as well as increased breastfeeding in Period II could have contributed to increased lung function, other unmeasured risk factors may have played a more dominant role in leading to a net decrease in lung function from Period I to Period II. Future studies are needed to identify these risk factors.

Impact of depression on quality of life in systemic lupus erythematosus patients

BackgroundDepression is common in systemic lupus erythematosus (SLE) and is an unmeasured risk factor, yet its symptoms can be neglected in standard disease evaluations. The purpose of this study was to assess the frequency and the impact of depression on quality of life in SLE patients. We recruited 32 patients with SLE and 15 healthy control volunteers in the study. The following investigations were undertaken in each patient: clinical and rheumatologic assessment, SLE Disease Activity Index-2k (SLEDAI-2k), Beck Depression Inventory (BDI), Short-Form Health Survey (SF-36) questionnaire, and routine laboratory tests.ResultsThere was a high percentage of depression (46.9%) in the SLE patients. Regarding quality of life (SF-36), there were significant affection of the physical and mental composite summary domains (PCS and MCS) scores in lupus patients compared with controls (P < 0.000 for both) with the same significant in depressed compared with non-depressed patients. SF-36 subscales (physical function, limit emotional, emotional wellbeing, and social function) were significantly affected in depressed lupus patients compared with non-depressed patients. There was a significant negative correlation between the score of MCS domain of SF-36 with BDI (P < 0.000) while positive correlation between SLEDAI score with depression score. In contrast, there were no significant correlations between MCS or PCS with age, duration of illness, or SLEDAI-2K.ConclusionsDepression is common in SLE patients and had a negative impact on quality of life particularly on MCS domain and positive correlation with disease severity score.Trial registrationThis study was registered on clinical trial with registration number: NCT03165682 https://clinicaltrials.gov/ct2/show/NCT03165682 on 24 May 2017.

Self-identified Race and COVID-19-Associated Acute Kidney Injury and Inflammation: a Retrospective Cohort Study of Hospitalized Inner-City COVID-19 Patients.

BackgroundBlack individuals have been disproportionately affected by the coronavirus disease 2019 (COVID-19). However, it remains unclear whether there are any biological factors that predispose Black patients to COVID-19-related morbidity and mortality.ObjectiveTo compare in-hospital morbidity, mortality, and inflammatory marker levels between Black and White hospitalized COVID-19 patients.Design and ParticipantsThis single-center retrospective cohort study analyzed data for Black and White patients aged ≥18 years hospitalized with a positive SARS-CoV-2 PCR test between March 1, 2020, and August 4, 2020.Main MeasuresThe exposure was self-identified race documented in the medical record. The primary outcome of was in-hospital death. Secondary outcomes included intensive care unit admission, hospital morbidities, and inflammatory marker levels.Key ResultsA total of 1,424 Black and White patients were identified. The mean ± SD age was 56.1 ± 17.4 years, and 663 (44.5%) were female. There were 683 (48.0%) Black and 741 (52.0%) White patients. In the univariate analysis, Black patients had longer hospital stays (8.1 ± 10.2 vs. 6.7 ± 8.3 days, p = 0.011) and tended to have higher rates of in-hospital death (11.0% vs. 7.3%), myocardial infarction (6.9% vs. 4.5%), pulmonary embolism (PE; 5.0% vs. 2.3%), and acute kidney injury (AKI; 39.4% vs. 23.1%) than White patients (p <0.05). However, after adjusting for potential confounders, only PE (adjusted odds ratio [aOR] 2.07, 95% CI, 1.13–3.79) and AKI (aOR 2.16, 95% CI, 1.57–2.97) were statistically significantly associated with Black race. In comparison with White patients, Black patients had statistically significantly higher peak plasma D-dimer (standardized β = 0.10), erythrocyte sedimentation rate (standardized β = 0.13), ferritin (standardized β = 0.09), and lactate dehydrogenase (standardized β = 0.11), after adjusting for potential confounders (p<0.05).ConclusionsBlack hospitalized COVID-19 patients had increased risks of developing PE and AKI and higher inflammatory marker levels compared with White patients. This observation may be explained by differences in the prevalence and severity of underlying comorbidities and other unmeasured biologic risk factors between Black and White patients. Future research is needed to investigate the mechanism of these observed differences in outcomes of severe COVID-19 infection in Black versus White patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06931-1.

Geostatistical analysis, web-based mapping, and environmental determinants of under-5 stunting: evidence from the 2014 Ghana Demographic and Health Survey

Stunting rates in children younger than 5 years are among the most important health indicators globally. At the national level, malnutrition accounts for about 40% of under-5 deaths in Ghana. Disease risk mapping provides opportunities for disease surveillance and targeted interventions. We aimed to estimate and map under-5 stunting prevalence in Ghana, with the goal of identifying communities at higher risk where interventions and further research can be targeted. For this modelling study, we used data from the 2014 Ghana Demographic and Health Survey. Analyses were done on 2734 children residing in 415 geographical clusters. The outcome variable was the number of stunted children younger than 5 years in each sampled cluster. We employed a Bayesian geostatistical model to investigate both measured and unmeasured spatial risk factors for child stunting, comparing the performance of non-spatial (adjusting for selected covariates without spatial correlation), spatial (including spatial correlation), and null spatial (without the selected covariates) models. We then visualised the stunting prevalence across Ghana by mapping the predicted prevalence and exceedance probabilities to resolutions as refined as 5 km × 5 km. In 2014, 535 (19·6%) of 2734 children surveyed in Ghana were stunted. Elevation (log odds mean -0·0017, 95% credible interval -0·0034 to -0·0001), precipitation (0·0403, 0·0192 to 0·0615), and aridity (-3·7013, -6·5478 to -0·8723) were environmental and climatic factors associated with stunting in the non-spatial model, but were not significant in the spatial model. Substantial geographical variations in prevalence of childhood stunting were found. The predicted mean stunting prevalence was 27·7% (SD 3·7%) with predicted prevalence ranging from 4·2% to 45·1% across Ghana. Children residing in parts of the Northern region were at highest risk of stunting, whereas parts of the Greater Accra, Brong-Ahafo, Ashanti, and Eastern regions showed some of the lowest prevalence. There are substantial geographical differences in childhood stunting across Ghana. Our prevalence maps can be used as an effective tool to identify communities that require targeted interventions by programme managers and implementers, as part of an overall strategy to reduce the burden of malnutrition in a country with limited public health resources. None.

Geospatial analysis, web-based mapping and determinants of prostate cancer incidence in Georgia counties: evidence from the 2012\u20132016 SEER data

BackgroundProstate cancer (CaP) cases are high in the United States. According to the American Cancer Society, there are an estimated number of 174,650 CaP new cases in 2019. The estimated number of deaths from CaP in 2019 is 31,620, making CaP the second leading cause of cancer deaths among American men with lung cancer been the first. Our goal is to estimate and map prostate cancer relative risk, with the ultimate goal of identifying counties at higher risk where interventions and further research can be targeted.MethodsThe 2012–2016 Surveillance, Epidemiology, and End Results (SEER) Program data was used in this study. Analyses were conducted on 159 Georgia counties. The outcome variable is incident prostate cancer. We employed a Bayesian geospatial model to investigate both measured and unmeasured spatial risk factors for prostate cancer. We visualised the risk of prostate cancer by mapping the predicted relative risk and exceedance probabilities. We finally developed interactive web-based maps to guide optimal policy formulation and intervention strategies.ResultsNumber of persons above age 65 years and below poverty, higher median family income, number of foreign born and unemployed were risk factors independently associated with prostate cancer risk in the non-spatial model. Except for the number of foreign born, all these risk factors were also significant in the spatial model with the same direction of effects. Substantial geographical variations in prostate cancer incidence were found in the study. The predicted mean relative risk was 1.20 with a range of 0.53 to 2.92. Individuals residing in Towns, Clay, Union, Putnam, Quitman, and Greene counties were at increased risk of prostate cancer incidence while those residing in Chattahoochee were at the lowest risk of prostate cancer incidence.ConclusionOur results can be used as an effective tool in the identification of counties that require targeted interventions and further research by program managers and policy makers as part of an overall strategy in reducing the prostate cancer burden in Georgia State and the United States as a whole.

Triangulating evidence on the role of perceived versus objective experiences of childhood adversity in psychopathology

Triangulating evidence on the role of perceived versus objective experiences of childhood adversity in psychopathology