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Biomarkers used to track benefits of anti-aging therapies can be misleading, suggests nematode study

Researchers followed the birth and death of tens of thousands of nematode worms using the ‘Lifespan Machine’, which collects lifespan data at unprecedented statistical resolution. They found that worms have at least two distinct ‘biological ages’, and that these have consistent correlations between each other, suggesting the existence of an invisible hierarchical structure that regulates the ageing process. The findings challenge the idea of living organisms having a single, universal biological age. It also means mean that biomarkers used to assess biological age can be changed by interventions such as diet, exercise, or drug treatments without actually turning a ‘fast ager’ into a ‘slow ager’. The study calls into question the use of ageing biomarkers — what exactly are they measuring?
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Effects of a Digital Patient Empowerment and Communication Tool on Metabolic Control in People With Type 2 Diabetes: The DeMpower Multicenter Ambispective Study

JMIR Diabetes. 2022 Oct 3;7(4):e40377. doi: 10.2196/40377.

ABSTRACT

BACKGROUND: Diabetes is a major health care problem, reaching epidemic numbers worldwide. Reducing hemoglobin A1c (HbA1c) levels to recommended targets is associated with a marked decrease in the risk of type 2 diabetes mellitus (T2DM)-related complications. The implementation of new technologies, particularly telemedicine, may be helpful to facilitate self-care and empower people with T2DM, leading to improved metabolic control of the disease.

OBJECTIVE: This study aimed to analyze the effect of a home digital patient empowerment and communication tool (DeMpower App) on metabolic control in people with inadequately controlled T2DM.

METHODS: The DeMpower study was multicenter with a retrospective (observational: 52 weeks of follow-up) and prospective (interventional: 52 weeks of follow-up) design that included people with T2DM, aged ≥18 and ≤80 years, with HbA1c levels ≥7.5% to ≤9.5%, receiving treatment with noninsulin antihyperglycemic agents, and able to use a smartphone app. Individuals were randomly assigned (2:1) to the DeMpower app-empowered group or control group. We describe the effect of empowerment on the proportion of patients achieving the study glycemic target, defined as HbA1c≤7.5% with a ≥0.5% reduction in HbA1c at week 24.

RESULTS: Due to the COVID-19 pandemic, the study was stopped prematurely, and 50 patients (33 in the DeMpower app-empowered group and 17 in the control group) were analyzed. There was a trend toward a higher proportion of patients achieving the study glycemic target (46% vs 18%; P=.07) in the DeMpower app group that was statistically significant when the target was HbA1c≤7.5% (64% vs 24%; P=.02) or HbA1c≤8% (85% vs 53%; P=.02). The mean HbA1c was significantly reduced at week 24 (-0.81, SD 0.89 vs -0.15, SD 1.03; P=.03); trends for improvement in other cardiovascular risk factors, medication adherence, and satisfaction were observed.

CONCLUSIONS: The results suggest that patient empowerment through home digital tools has a potential effect on metabolic control, which might be even more relevant during the COVID-19 pandemic and in a digital health scenario.

PMID:36190763 | DOI:10.2196/40377

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A dynamical scan-path model for task-dependence during scene viewing

Psychol Rev. 2022 Oct 3. doi: 10.1037/rev0000379. Online ahead of print.

ABSTRACT

In real-world scene perception, human observers generate sequences of fixations to move image patches into the high-acuity center of the visual field. Models of visual attention developed over the last 25 years aim to predict two-dimensional probabilities of gaze positions for a given image via saliency maps. Recently, progress has been made on models for the generation of scan paths under the constraints of saliency as well as attentional and oculomotor restrictions. Experimental research demonstrated that task constraints can have a strong impact on viewing behavior. Here, we propose a scan-path model for both fixation positions and fixation durations, which include influences of task instructions and interindividual differences. Based on an eye-movement experiment with four different task conditions, we estimated model parameters for each individual observer and task condition using a fully Bayesian dynamical modeling framework using a joint spatial-temporal likelihood approach with sequential estimation. Resulting parameter values demonstrate that model properties such as the attentional span are adjusted to task requirements. Posterior predictive checks indicate that our dynamical model can reproduce task differences in scan-path statistics across individual observers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:36190753 | DOI:10.1037/rev0000379

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Association of Prior Intracerebral Hemorrhage With Major Adverse Cardiovascular Events

JAMA Netw Open. 2022 Oct 3;5(10):e2234215. doi: 10.1001/jamanetworkopen.2022.34215.

ABSTRACT

IMPORTANCE: Patients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population.

OBJECTIVE: To evaluate the risk of a MACE for patients with a prior ICH compared with the general population.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study identified 8991 patients with a first ICH in the Danish Stroke Registry from January 1, 2005, to June 30, 2018, who were aged 45 years or older and survived more than 30 days after an ICH. Patients in this ICH cohort were matched 1:40 on age, sex, and ICH-onset date with a comparison cohort of 359 185 individuals from the general population without a prior ICH. Both cohorts were followed up for 6 months or more until December 31, 2018, for outcomes using registry data. Data were analyzed from October 1, 2021, to July 19, 2022.

EXPOSURES: Intracerebral hemorrhage identified by a nationwide clinical database.

MAIN OUTCOMES AND MEASURES: The main outcomes were ICH, ischemic stroke, myocardial infarction, and a composite of MACEs. For each outcome, a case-control study nested within the cohorts was also performed, adjusting for time-varying exposures and potential confounders. Crude absolute event rates per 100 person-years, adjusted hazard ratios (aHRs) and 95% CIs and, in the nested case-control analyses, crude and adjusted odds ratios and 95% CIs were calculated.

RESULTS: The ICH cohort (n = 8991; 4814 men [53.5%]; mean [SD] age, 70.7 [11.5] years) had higher event rates than the comparison cohort (n = 359 185; 192 256 men [53.5%]; mean [SD] age, 70.7 [11.5] years) for MACEs (4.16 [95% CI, 3.96-4.37] per 100 person-years vs 1.35 [95% CI, 1.33-1.36] per 100 person-years; aHR, 3.13 [95% CI, 2.97-3.30]), ischemic stroke (1.52 [95% CI, 1.40-1.65] per 100 person-years vs 0.56 [95% CI, 0.55-0.57] per 100 person-years; aHR, 2.64 [95% CI, 2.43-2.88]), and ICH (1.44 [95% CI, 1.32-1.56] per 100 person-years vs 0.06 [95% CI, 0.06-0.07] per 100 person-years; aHR, 23.49 [95% CI, 21.12-26.13]) but not myocardial infarction (0.52 [95% CI, 0.45-0.60] per 100 person-years vs 0.48 [95% CI, 0.47-0.49] per 100 person-years; aHR, 1.12 [95% CI, 0.97-1.29]). Nested case-control analyses returned risk estimates of similar magnitude as the cohort analyses.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that Danish patients with a prior ICH had statistically significantly higher rates of MACEs than the general population, indicating a need for attention to optimal secondary prevention with blood pressure lowering and antithrombotic and statin therapies after an ICH in clinical research and practice.

PMID:36190733 | DOI:10.1001/jamanetworkopen.2022.34215

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Association of Appendicitis Incidence With Warmer Weather Independent of Season

JAMA Netw Open. 2022 Oct 3;5(10):e2234269. doi: 10.1001/jamanetworkopen.2022.34269.

ABSTRACT

IMPORTANCE: Acute appendicitis is a common cause of abdominal pain and the most common reason for emergency surgery in several countries. Increased cases during summer months have been reported.

OBJECTIVE: To investigate the incidence of acute appendicitis by considering local temperature patterns in geographic regions with different climate over several years.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used insurance claims data from the MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental and Coordination of Benefits Database from January 1, 2001, to December 31, 2017. The cohort included individuals at risk for appendicitis who were enrolled in US insurance plans that contribute data to the MarketScan databases. Cases of appendicitis in the inpatient, outpatient, and emergency department settings were identified using International Classification of Diseases, Ninth Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. Local weather data were obtained for individuals living in a metropolitan statistical area (MSA) from the Integrated Surface Database. Associations were characterized using a fixed-effects generalized linear model based on a negative binomial distribution. The model was adjusted for age, sex, and day of week and included fixed effects for year and MSA. The generalized linear model was fit with a piecewise linear model by searching each 0.56 °C in temperature for change points. To further isolate the role of temperature, observed temperature was replaced with the expected temperature and the deviation of the observed temperature from the expected temperature for a given city on a given day of year. Data were analyzed from October 1, 2021, to July 31, 2022.

MAIN OUTCOMES AND MEASURES: The primary outcome was the daily number of appendicitis cases in a given city stratified by age and sex, with mean temperature in the MSA over the previous 7 days as the independent variable.

RESULTS: A total of 450 723 744 person-years at risk and 689 917 patients with appendicitis (mean [SD] age, 35 [18] years; 347 473 male [50.4%] individuals) were included. Every 5.56 °C increase in temperature was associated with a 1.3% increase in the incidence of appendicitis (incidence rate ratio [IRR], 1.01; 95% CI, 1.01-1.02) when temperatures were 10.56 °C or lower and a 2.9% increase in incidence (IRR, 1.03; 95% CI, 1.03-1.03) for temperatures higher than 10.56 °C. In terms of temperature deviations, a higher-than-expected temperature increase greater than 5.56 °C was associated with a 3.3% (95% CI, 1.0%-5.7%) increase in the incidence of appendicitis compared with days with near-0 deviations.

CONCLUSIONS AND RELEVANCE: Results of this cohort study observed seasonality in the incidence of appendicitis and found an association between increased incidence and warmer weather. These results could help elucidate the mechanism of appendicitis.

PMID:36190731 | DOI:10.1001/jamanetworkopen.2022.34269

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Association of Household Deprivation, Comorbidities, and COVID-19 Hospitalization in Children in Germany, January 2020 to July 2021

JAMA Netw Open. 2022 Oct 3;5(10):e2234319. doi: 10.1001/jamanetworkopen.2022.34319.

ABSTRACT

IMPORTANCE: Adults in disadvantaged socioeconomic positions have elevated risks of a severe course of COVID-19, but it is unclear whether this holds true for children.

OBJECTIVE: To investigate whether young people from disadvantaged households have a higher risk of COVID-19 hospitalization and whether differences were associated with comorbidities that predispose children to severe courses.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included all children and adolescents (aged 0-18 years) who were enrolled in a statutory health insurance carrier in Germany during the observation period of January 1, 2020, to July 13, 2021. Logistic regressions were calculated to compare children from households with and without an indication of poverty. Age, sex, days under observation, nationality, and comorbidities (eg, obesity, diabetes) were controlled for to account for explanatory factors.

EXPOSURES: Disadvantage on the household level was assessed by the employment status of the insurance holder (ie, employed, long- or short-term unemployed, low-wage employment, economically inactive). Socioeconomic characteristics of the area of residence were also assessed.

MAIN OUTCOMES AND MEASURES: Daily hospital diagnoses of COVID-19 (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes U07.1 and U07.2) were recorded. Comorbidities were assessed using inpatient and outpatient diagnoses contained in the insurance records.

RESULTS: A total of 688 075 children and adolescents were included, with a mean (SD) age of 8.3 (5.8) years and 333 489 (48.4%) female participants. COVID-19 hospital diagnosis was a rare event (1637 participants [0.2%]). Children whose parents were long-term unemployed were 1.36 (95% CI, 1.22-1.51) times more likely than those with employed parents to be hospitalized. Elevated odds were also found for children whose parents had low-wage employment (odds ratio, 1.29; 95% CI, 1.05-1.58). Those living in low-income areas had 3.02 (95% CI, 1.73-5.28) times higher odds of hospitalization than those in less deprived areas. Comorbidities were associated with hospitalization, but their adjustment did not change main estimates for deprivation.

CONCLUSIONS AND RELEVANCE: In this cohort study, children who had parents who were unemployed and those who lived in low-income areas were at higher risk of COVID-19 hospitalization. This finding suggests that attention must be paid to children with SARS-CoV-2 from vulnerable families and closer monitoring should be considered. A number of explanatory factors, including comorbidities, were taken into account, but their analysis yielded no clear picture about underlying processes.

PMID:36190730 | DOI:10.1001/jamanetworkopen.2022.34319

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Comparison of a Target Trial Emulation Framework vs Cox Regression to Estimate the Association of Corticosteroids With COVID-19 Mortality

JAMA Netw Open. 2022 Oct 3;5(10):e2234425. doi: 10.1001/jamanetworkopen.2022.34425.

ABSTRACT

IMPORTANCE: Communication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data.

OBJECTIVE: To compare a modern method for statistical inference, including a target trial emulation framework and doubly robust estimation, with approaches common in the clinical literature, such as Cox proportional hazards models.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used longitudinal electronic health record data for outcomes at 28-days from time of hospitalization within a multicenter New York, New York, hospital system. Participants included adult patients hospitalized between March 1 and May 15, 2020, with COVID-19 and not receiving corticosteroids for chronic use. Data were analyzed from October 2021 to March 2022.

EXPOSURES: Corticosteroid exposure was defined as more than 0.5 mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, exposures were corticosteroids for 6 days if and when a patient met criteria for severe hypoxia vs no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models varied by study design (no time frame, 1 day, and 5 days from time of severe hypoxia).

MAIN OUTCOMES AND MEASURES: The main outcome was 28-day mortality from time of hospitalization. The association of corticosteroids with mortality for patients with moderate to severe COVID-19 was assessed using the World Health Organization (WHO) meta-analysis of corticosteroid randomized clinical trials as a benchmark.

RESULTS: A total of 3298 patients (median [IQR] age, 65 [53-77] years; 1970 [60%] men) were assessed, including 423 patients who received corticosteroids at any point during hospitalization and 699 patients who died within 28 days of hospitalization. Target trial emulation analysis found corticosteroids were associated with a reduced 28-day mortality rate, from 32.2%; (95% CI, 30.9%-33.5%) to 25.7% (95% CI, 24.5%-26.9%). This estimate is qualitatively identical to the WHO meta-analysis odds ratio of 0.66 (95% CI, 0.53-0.82). Hazard ratios using methods comparable with current corticosteroid research range in size and direction, from 0.50 (95% CI, 0.41-0.62) to 1.08 (95% CI, 0.80-1.47).

CONCLUSIONS AND RELEVANCE: These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing the study and analyzing the data based on principles that are different from the current standard in clinical research.

PMID:36190729 | DOI:10.1001/jamanetworkopen.2022.34425

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Anesthesia Care for Cataract Surgery in Medicare Beneficiaries

JAMA Intern Med. 2022 Oct 3. doi: 10.1001/jamainternmed.2022.4333. Online ahead of print.

ABSTRACT

IMPORTANCE: Cataract surgery in the US is routinely performed with anesthesia care, whereas anesthesia care for other elective, low-risk, outpatient procedures is applied more selectively.

OBJECTIVE: To identify predictors of anesthesia care in Medicare beneficiaries undergoing cataract surgery and evaluate anesthesia care for cataract surgery compared with other elective, low-risk, outpatient procedures.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective observational cohort study included Medicare beneficiaries 66 years or older who underwent cataract surgery in 2017. The data were analyzed from August 2020 through May 2021.

INTERVENTIONS (FOR CLINICAL TRIALS) OR EXPOSURES (FOR OBSERVATIONAL STUDIES): Anesthesia care during elective, low-risk, outpatient procedures.

MAIN OUTCOMES AND MEASURES: Prevalence of anesthesia care during cataract surgery compared with other low-risk procedures; association of anesthesia care with patient, clinician, and health system characteristics; and proportion of patients experiencing a systemic complication within 7 days of cataract surgery compared with patients undergoing other low-risk procedures.

RESULTS: Among 36 652 cataract surgery patients, the mean (SD) age was 74.7 (6.1) years; 21 690 (59.2%) were female; 2200 (6.6%) were Black and 32 049 (87.4%) were White. Anesthesia care was more common among patients undergoing cataract surgery compared with patients undergoing other low-risk procedures (89.8% vs range of <1% to 70.2%). Neither the patient’s age (adjusted odds ratio, 1.01; 95% CI, 1.00-1.02; P = .01) nor Charlson Comorbidity Index (CCI) score (CCI of ≥3: adjusted odds ratio, 1.06; 95% CI, 0.95-1.18; P = .28; reference, CCI score of 0-1) was strongly associated with anesthesia care for cataract surgery, but a model comprising a single variable identifying the ophthalmologist predicted anesthesia care with a C statistic of 0.96. Approximately 6.0% of ophthalmologists never used anesthesia care, 76.6% always used anesthesia care, and 17.4% used it for only a subset of patients. Fewer cataract surgery patients experienced systemic complications within 7 days (2833 [7.7%]), even when limited to patients of ophthalmologists who never used anesthesia care (108 [7.4%]), than patients undergoing other low-risk procedures (range, 13.2%-52.2%).

CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that systemic complications occurred less frequently after cataract surgery compared with other elective, low-risk, outpatient procedures during which anesthesia care was less commonly used. Anesthesia care was not associated with patient characteristics, such as older age or worse health status, but with the ophthalmologists’ usual approach to cataract surgery sedation. The study findings suggest an opportunity to use anesthesia care more selectively in patients undergoing cataract surgery.

PMID:36190717 | DOI:10.1001/jamainternmed.2022.4333

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The multiple mediating effects of grit and learning agility on academic burnout and learning engagement among Korean university students: a cross-sectional study

Ann Med. 2022 Dec;54(1):2710-2724. doi: 10.1080/07853890.2022.2122551.

ABSTRACT

INTRODUCTION: This article reports the results of a study conducted to assess the mediating effects of grit and learning agility on the relationship between academic burnout and learning engagement among undergraduate students.

METHODS: A cross-sectional survey was conducted using a self-report questionnaire. Undergraduate students (N = 344) were recruited from one university in South Korea (58.0% female; average age 21.43) to complete assessments of academic burnout, grit, learning agility, and learning engagement. Data were analysed using descriptive statistics, Pearson’s correlation coefficient, hierarchical regression and bootstrapping to verify the multiple parallel mediation effect.

RESULTS: We found that the direct effect of academic burnout on learning engagement (B= -0.26, p<.001) and the indirect effect of academic burnout as mediated by learning agility (B= -0.13; 95% CI, -0.20∼-0.06) were significant. This finding confirmed that 33.3% of the total effect of academic burnout on learning engagement was the result of indirect effects via learning agility.

CONCLUSION: These results indicate the necessity of developing an educational programme that focuses not only on reducing academic burnout but also on improving learning agility to increase undergraduate students’ learning engagement. This study contributes to the development of a curriculum aimed at increasing the effectiveness of university education, promoting learning engagement, and reducing academic burnout.KEY MESSAGEOur study reports that academic burnout has both a direct effect on learning engagement and an indirect effect via learning agility. Learning agility mediates the relationship between academic burnout and learning engagement among undergraduate students.Although grit has been reported by many previous studies to mediate the relationship between the tendency to pursue happiness and the willingness to continue learning and effectively improving one’s academic achievement and ability, our study did not find any mediating effect via grit in this context.

PMID:36190716 | DOI:10.1080/07853890.2022.2122551

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Racial and Ethnic Differences in Amyloid PET Positivity in Individuals With Mild Cognitive Impairment or Dementia: A Secondary Analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Cohort Study

JAMA Neurol. 2022 Oct 3. doi: 10.1001/jamaneurol.2022.3157. Online ahead of print.

ABSTRACT

IMPORTANCE: Racial and ethnic groups with higher rates of clinical Alzheimer disease (AD) are underrepresented in studies of AD biomarkers, including amyloid positron emission tomography (PET).

OBJECTIVE: To compare amyloid PET positivity among a diverse cohort of individuals with mild cognitive impairment (MCI) or dementia.

DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS), a single-arm multisite cohort study of Medicare beneficiaries who met appropriate-use criteria for amyloid PET imaging between February 2016 and September 2017 with follow-up through January 2018. Data were analyzed between April 2020 and January 2022. This study used 2 approaches: the McNemar test to compare amyloid PET positivity proportions between matched racial and ethnic groups and multivariable logistic regression to assess the odds of having a positive amyloid PET scan. IDEAS enrolled participants at 595 US dementia specialist practices. A total of 21 949 were enrolled and 4842 (22%) were excluded from the present analysis due to protocol violations, not receiving an amyloid PET scan, not having a positive or negative scan, or because of small numbers in some subgroups.

EXPOSURES: In the IDEAS study, participants underwent a single amyloid PET scan.

MAIN OUTCOMES AND MEASURES: The main outcomes were amyloid PET positivity proportions and odds.

RESULTS: Data from 17 107 individuals (321 Asian, 635 Black, 829 Hispanic, and 15 322 White) with MCI or dementia and amyloid PET were analyzed between April 2020 and January 2022. The median (range) age of participants was 75 (65-105) years; 8769 participants (51.3%) were female and 8338 (48.7%) were male. In the optimal 1:1 matching analysis (n = 3154), White participants had a greater proportion of positive amyloid PET scans compared with Asian participants (181 of 313; 57.8%; 95% CI, 52.3-63.2 vs 142 of 313; 45.4%; 95% CI, 39.9-50.9, respectively; P = .001) and Hispanic participants (482 of 780; 61.8%; 95% CI, 58.3-65.1 vs 425 of 780; 54.5%; 95% CI, 51.0-58.0, respectively; P = .003) but not Black participants (359 of 615; 58.4%; 95% CI, 54.4-62.2 vs 333 of 615; 54.1%; 95% CI, 50.2-58.0, respectively; P = .13). In the adjusted model, the odds of having a positive amyloid PET scan were lower for Asian participants (odds ratio [OR], 0.47; 95% CI, 0.37-0.59; P < .001), Black participants (OR, 0.71; 95% CI, 0.60-0.84; P < .001), and Hispanic participants (OR, 0.68; 95% CI, 0.59-0.79; P < .001) compared with White participants.

CONCLUSIONS AND RELEVANCE: Racial and ethnic differences found in amyloid PET positivity among individuals with MCI and dementia in this study may indicate differences in underlying etiology of cognitive impairment and guide future treatment and prevention approaches.

PMID:36190710 | DOI:10.1001/jamaneurol.2022.3157