Carotid Artery Stiffness Mechanisms Associated With Cardiovascular Disease Events and Incident Hypertension: the MESA

Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000–2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson’s elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson’s elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Results: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09–1.34] P <0.001) events while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.10). Analysis of participants who were normotensive (blood pressure <130/80, no antihypertensives) at baseline exam (n=2122) found higher load-dependent stiffness was also associated with significantly higher incidence of hypertension (hazard ratio, 1.53 [95% CI, 1.35–1.75] P <0.001) while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.16). Conclusions: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.

Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Objective: Intensive glycemic control reduces risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces risk of lower extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFU) and lower extremity amputations (LEA) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p>Research Design and Methods: DCCT participants [n=1441] completed 6.5 years on average of intensive vs conventional diabetes treatment, after which 1408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. </p> <p>Results: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFU (Hazard Ratio [HR] 0.77, 95% CI 0.60 to 0.97), and a similar magnitude but nonsignificant risk reduction for first recorded DFU (HR 0.78, 95% CI 0.59 to 1.03) and first LEA (HR 0.70, 95% CI 0.36 to 1.36). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity and cardiovascular autonomic neuropathy were associated with higher DFU risk; eGFR < 60 mL/min/1.73 m², albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (p<0.05).</p> <p>Conclusions: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.</p>

MRI-Based Random Survival Forest Model Improves the Prediction of Progression-Free Survival to Induction Chemotherapy plus Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

BackgroundThe present study aimed to explore the application value of random survival forest (RSF) model and Cox model in predicting the progression-free survival (PFS) among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT).MethodsEligible LANPC patients underwent magnetic resonance imaging (MRI) scan before treatment were subjected to radiomics feature extraction. Radiomics and clinical features of patients in the training cohort were subjected to RSF analysis to predict PFS and were tested in the testing cohort. The performance of an RSF model with clinical and radiologic predictors was assessed with the area under the receiver operating characteristic (ROC) curve (AUC) and Delong test and compared with Cox models based on clinical and radiologic parameters. Further, the Kaplan-Meier method was used for risk stratification of patients.ResultsA total of 294 LANPC patients (206 in the training cohort; 88 in the testing cohort) were enrolled and underwent magnetic resonance imaging (MRI) scans before treatment. The AUC value of the clinical Cox model, radiomics Cox model, clinical + radiomics Cox model, and clinical + radiomics RSF model in predicting 3- and 5-year PFS for LANPC patients was [0.545 vs 0.648 vs 0.648 vs 0.899 (training cohort), and 0.566 vs 0.736 vs 0.73 vs 0.861 (testing cohort); 0.556 vs 0.604 vs 0.611 vs 0.897 (training cohort), and 0.591 vs 0.661 vs 0.676 vs 0.847 (testing cohort), respectively]. Delong test showed that the RSF model and the other three Cox models were statistically significant, and the RSF model markedly improved prediction performance (P<0.001). Additionally, the PFS of the high-risk group was lower than that of the low-risk group in the RSF model (P<0.001), while comparable in the Cox model (P>0.05).ConclusionThe RSF model may be a potential tool for prognostic prediction and risk stratification of LANPC patients.

MIND diet and the risk of dementia: a population-based study

Background Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed to address these issues by studying the associations over cumulative time periods, which may provide insight into possible reverse causality, and by using both historical and more contemporary dietary data as this could give insight into confounding since historical data may be less affected by lifestyle factors. Methods In the population-based Rotterdam Study, dietary intake was assessed using validated food frequency questionnaires in 5375 participants between 1989 and 1993 (baseline I) and in a largely non-overlapping sample in 2861 participants between 2009 and 2013 (baseline II). We calculated the MIND diet score and studied its association with the risk of all-cause dementia, using Cox models. Incident all-cause dementia was recorded until 2018. Results During a mean follow-up of 15.6 years from baseline I, 1188 participants developed dementia. A higher MIND diet score at baseline I was associated with a lower risk of dementia over the first 7 years of follow-up (hazard ratio (HR) [95% confidence interval (CI)] per standard deviation (SD) increase, 0.85 [0.74, 0.98]), but associations disappeared over longer follow-up intervals. The mean follow-up from baseline II was 5.9 years during which 248 participants developed dementia. A higher MIND diet score at baseline II was associated with a lower risk of dementia over every follow-up interval, but associations slightly attenuated over time (HR [95% CI] for 7 years follow-up per SD increase, 0.76 [0.66, 0.87]). The MIND diet score at baseline II was more strongly associated with the risk of dementia than the MIND diet score at baseline I. Conclusion Better adherence to the MIND diet is associated with a decreased risk of dementia within the first years of follow-up, but this may in part be explained by reverse causality and residual confounding by lifestyle. Further research is needed to unravel to which extent the MIND diet may affect the risk of dementia.

Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Objective: Intensive glycemic control reduces risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces risk of lower extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFU) and lower extremity amputations (LEA) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p>Research Design and Methods: DCCT participants [n=1441] completed 6.5 years on average of intensive vs conventional diabetes treatment, after which 1408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. </p> <p>Results: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFU (Hazard Ratio [HR] 0.77, 95% CI 0.60 to 0.97), and a similar magnitude but nonsignificant risk reduction for first recorded DFU (HR 0.78, 95% CI 0.59 to 1.03) and first LEA (HR 0.70, 95% CI 0.36 to 1.36). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity and cardiovascular autonomic neuropathy were associated with higher DFU risk; eGFR < 60 mL/min/1.73 m², albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (p<0.05).</p> <p>Conclusions: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.</p>

The Effectiveness of a Diverse COVID-19 Vaccine Portfolio and Its Impact on the Persistence of Positivity and Length of Hospital Stays: The Veneto Region’s Experience

The vaccination campaign for the Veneto region (northeastern Italy) started on 27 December 2020. As of early December 2021, 75.1% of the whole Veneto population has been fully vaccinated. Vaccine efficacy has been demonstrated in many clinical trials, but reports on real-world contexts are still necessary. We conducted a retrospective cohort study on 2,233,399 residents in the Veneto region to assess the reduction in the COVID-19 burden, taking different outcomes into consideration. First, we adopted a non-brand-specific approach borrowed from survival analysis to estimate the effectiveness of vaccination against SARS-CoV-2 in preventing infections, hospitalizations, and deaths. We used t-tests and multivariate regressions to examine vaccine impact on breakthrough infections, in terms of the persistence of positivity and the length of hospital stays. Evidence emerging from this study suggests that unvaccinated individuals are significantly more likely to become infected, need hospitalization, and are at a higher risk of death from COVID-19 than those given at least one dose of vaccine. Cox models indicate that the effectiveness of full vaccination is 88% against infection, 94% against hospitalization, and 95% against death. Multivariate regressions suggest that vaccination is significantly correlated with a shorter period of positivity and shorter hospital stays, with each step toward completion of the vaccination cycle coinciding with a reduction of 3.3 days in the persistence of positivity and 2.3 days in the length of hospital stay.

COVID-19 vaccine effectiveness among healthcare workers in Portugal: results from a hospital-based cohort study, December 2020 to November 2021

Introduction: Healthcare workers (HCW) were amongst the first prioritized for COVID-19 vaccination but data on COVID–19 vaccine effectiveness among HCW is still limited. This study aims to estimate the COVID–19 vaccine effectiveness (VE) against SARS–CoV–2 symptomatic infection among HCW from Portuguese hospitals. Methods: In this prospective cohort study, we analysed data from HCW (all professional categories) from two central hospitals in the Lisbon and Tagus Valley and Centre regions of mainland Portugal between December 2020 and November 2021. VE against symptomatic SARS–CoV–2 infection was estimated as one minus the confounder adjusted hazard ratios by Cox models considering age group, sex, presence of chronic disease and occupational exposure to patients diagnosed with COVID–19 as adjustment variables. Results: During the 11 months of follow up, the 2213 HCW contributed a total of 1950 person-years at risk and 171 SARS–CoV–2 events occurred. The COVID–19 incidence rate for unvaccinated HCW was 348.7 per 1000 person-years while for fully vaccinated HCW was 43.0 per 1000 person-years. We observed a VE against symptomatic SARS–CoV–2 infection of 73.9% (95% CI: 26.2–90.8%) for complete vaccination status. Conclusion: This cohort study found a high COVID-19 VE against symptomatic SARS–CoV–2 infection in Portuguese HCW, which is in concordance with previous studies from other countries. Monitoring of VE in this HCW cohort continues during the winter 2021/2022 to evaluate potential VE decay and booster vaccine effect. Keywords: Vaccine effectiveness, SARS–CoV–2 , COVID–19, symptomatic infection, healthcare workers.

Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

OBJECTIVE Intensive glycemic control reduces the risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces the risk of lower-extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFUs) and lower-extremity amputations (LEAs) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS DCCT participants (n = 1,441) completed 6.5 years on average of intensive versus conventional diabetes treatment, after which 1,408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox proportional hazard regression models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. RESULTS Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFUs (hazard ratio 0.77 [95% CI 0.60, 0.97]) and a similar magnitude but nonsignificant risk reduction for first-recorded DFUs (0.78 [0.59, 1.03]) and first LEAs (0.70 [0.36, 1.36]). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity, and cardiovascular autonomic neuropathy were associated with higher DFU risk; estimated glomerular filtration rate &lt;60 mL/min/1.73 m2, albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (P &lt; 0.05). CONCLUSIONS Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.

Glycemic Variability Is Associated With All-Cause Mortality In COVID-19 Patients With ARDSFindings From The COVAS Cohort

There is high mortality among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease 19 (COVID-19). Important factors for COVID-19 mortality are diabetes status and elevated fasting plasma glucose (FPG). However, the effect of glycemic variability on survival has not been explored in patients with COVID-19 and ARDS. This single-centre cohort-study compared several metrics of daily glycemic variability (DGV) for goodness-of-fit in patients requiring mechanical ventilation due to COVID-19 ARDS in the ICU at University Hospital Aachen, Germany. 106 patients had moderate to severe ARDS (P/F ratio median [IQR]: 112 [87-148] mmHg). Continuous HRs showed a proportional increase in mortality risk with DGV. Multivariable unadjusted and adjusted Cox-models showed a statistically significant difference in mortality for DGV (HR: 1.02, (P)<0.001, LR(P)<0.001; HR: 1.016, (P)=0.001, LR(P)<0.001, respectively). Kaplan-Meier estimators yielded a shorter median survival (25 vs. 87 days) and higher likelihood of death (75% vs. 31%) in patients with DGV ≥ 25.5mg/dl (P<0.0001). High glycemic variability during ICU admission is associated with significant increase in all-cause mortality for patients admitted with COVID-19 ARDS to the ICU. This effect persisted even after adjustment for clinically predetermined confounders, including diabetes, procalcitonin and FPG levels at baseline.

Adherence to Social-Distancing and Personal Hygiene Behavior Guidelines and Risk of COVID-19 Diagnosis: Evidence From the Understanding America Study

Objectives. To assess the association between individual-level adherence to social-distancing and personal hygiene behaviors recommended by public health experts and subsequent risk of COVID-19 diagnosis in the United States. Methods. Data are from waves 7 through 26 (June 10, 2020–April 26, 2021) of the Understanding America Study COVID-19 survey. We used Cox models to assess the relationship between engaging in behaviors considered high risk and risk of COVID-19 diagnosis. Results. Individuals engaging in behaviors indicating lack of adherence to social-distancing guidelines, especially those related to large gatherings or public interactions, had a significantly higher risk of COVID-19 diagnosis than did those who did not engage in these behaviors. Each additional risk behavior was associated with a 9% higher risk of COVID-19 diagnosis (hazard ratio [HR] = 1.09; 95% confidence interval [CI] = 1.05, 1.13). Results were similar after adjustment for sociodemographic characteristics and local infection rates. Conclusions. Personal mitigation behaviors appear to influence the risk of COVID-19, even in the presence of social factors related to infection risk. Public Health Implications. Our findings emphasize the importance of individual behaviors for preventing COVID-19, which may be relevant in contexts with low vaccination. (Am J Public Health. 2022;112(1):169–178. https://doi.org/10.2105/AJPH.2021.306565 )