A multimodal deep learning model for cardiac resynchronisation therapy response prediction

We present a novel multimodal deep learning framework for cardiac resynchronisation therapy (CRT) response prediction from 2D echocardiography and cardiac magnetic resonance (CMR) data. The proposed method first uses the ‘nnU-Net’ segmentation model to extract segmentations of the heart over the full cardiac cycle from the two modalities. Next, a multimodal deep learning classifier is used for CRT response prediction, which combines the latent spaces of the segmentation models of the two modalities. At test time, this framework can be used with 2D echocardiography data only, whilst taking advantage of the implicit relationship between CMR and echocardiography features learnt from the model. We evaluate our pipeline on a cohort of 50 CRT patients for whom paired echocardiography/CMR data were available, and results show that the proposed multimodal classifier results in a statistically significant improvement in accuracy compared to the baseline approach that uses only 2D echocardiography data. The combination of multimodal data enables CRT response to be predicted with 77.38% accuracy (83.33% sensitivity and 71.43% specificity), which is comparable with the current state-of-the-art in machine learning-based CRT response prediction. Our work represents the first multimodal deep learning approach for CRT response prediction.     

Association of Self-reported Walking Pace With Type 2 Diabetes Incidence in the UK Biobank Prospective Cohort Study

ObjectiveTo investigate the association between self-reported walking pace and type 2 diabetes (T2D) incidence and whether it differed by physical activity levels and walking time.MethodsThere were 162,155 participants (mean age, 57.1 years; 54.9% women) from the UK Biobank prospective study, recruited between 2006 and 2010, included in the study. Walking pace was self-reported and classified as brisk, average, or slow. Total physical activity and walking time were self-reported using the International Physical Activity Questionnaire. Association between walking pace and T2D incidence and the potential moderating role of physical activity and walking time were investigated using Cox proportional hazards models.ResultsThe median follow-up was 7.4 (interquartile range, 6.7 to 8.2) years. There were 4442 participants in whom T2D developed during the follow-up period. In the fully adjusted model (sociodemographic factors, diet, body mass index, and physical activity), average walking pace (hazard ratio [HR], 1.28; 95% CI, 1.14 to 1.44) and slow walking pace (HR, 1.91; 95% CI, 1.62 to 2.24) were associated with a higher T2D risk compared with brisk walking among women. Among men, average walking pace (HR, 1.28; 95% CI, 1.17 to 1.40) and slow walking pace (HR, 1.73; 95% CI, 1.50 to 1.99) were also associated with higher T2D risk. Compared with slow walkers, brisk walkers have the same diabetes incidence rate 18.6 and 16.0 years later, for women and men, respectively.ConclusionAverage and slow walking pace was associated with a higher risk of incident T2D in both men and women, independent of major confounding factors. The associations were consistent across different physical activity levels and walking time.     

Cardiometabolic Health Outcomes Associated With Discordant Visceral and Liver Fat Phenotypes: Insights From the Dallas Heart Study and UK Biobank

ObjectiveTo evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts.Patients and MethodsParticipants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable-adjusted regression and were replicated in the independent UK Biobank.ResultsThe Dallas Heart Study included 2064 participants (mean ± SD age, 44±9 years; 54% female; 47% black). High VAT–high LF and high VAT–low LF were associated with prevalent atherosclerosis, whereas low VAT–high LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VAT–high LF and high VAT–low LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VAT–high LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N=22,354; April 2014-May 2020), only high VAT–low LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]).ConclusionAlthough VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual.     

Association of Lifestyle Behaviors With Hearing Loss: The UK Biobank Cohort Study

ObjectiveTo examine the combined association of five healthy lifestyle behaviors with hearing loss (HL) in the UK Biobank cohort, established between 2006 and 2010 in the United Kingdom.MethodsThis longitudinal analysis included 61,958 participants aged 40 to 70 years from April 2007 to December 2016. The healthy behaviors examined were: never smoking, high level of physical activity, high diet quality, moderate alcohol intake, and optimal sleep. Hearing loss was self-reported at baseline and in any physical exam during the follow-up.ResultsOver a median follow-up of 3.9±2.5 years, 3072 (5.0%) participants reported incident HL. After adjustment for potential confounders, including age, social factors, exposure to high-intensity noise, ototoxic medication, and comorbidity, the HRs of HL associated with having 1, 2, 3, and 4 to 5 vs 0 behaviors were: 0.85 (95% CI, 0.75 to 0.96), 0.85 (95% CI, 0.75 to 0.96), 0.82 (95% CI, 0.71 to 0.94), and 0.80 (95% CI, 0.67 to 0.97), respectively (P for trend, 0.02). We estimated that the population attributable risk percent for not adhering to any five low-risk lifestyle behaviors was 15.6%.ConclusionIn this large study, an increasing number of healthy behaviors was associated with decreased risk of HL.     

Prognostic Value of Cardiac Magnetic Resonance Imaging in Acute Coronary Syndrome Patients With Troponin Elevation and Nonobstructive Coronary Arteries

ObjectiveTo define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses.MethodsCardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a “working diagnosis” of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 μg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality.ResultsCardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with “true” MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction.ConclusionsCardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.     

Comparative Relevance of Physical Fitness and Adiposity on Life Expectancy: A UK Biobank Observational Study

ObjectiveTo investigate the extent to which 2 measures of physical fitness—walking pace and handgrip strength—are associated with life expectancy across different levels of adiposity, as the relative importance of physical fitness and adiposity on health outcomes is still debated.Patients and MethodsUsual walking pace (self-defined as slow, steady/average, brisk), dynamometer-assessed handgrip strength, body mass index (BMI), waist circumference, and body-fat percentage determined at baseline in the UK Biobank prospective cohort study (March 13, 2006, to January 31, 2016). Life expectancy was estimated at 45 years of age.ResultsThe median age and BMI of the 474,919 participants included in this analysis were 58.2 years and 26.7 kg/m², respectively; over a median follow-up of 6.97 years, 12,823 deaths occurred. Participants reporting brisk walking pace had longer life expectancies across all levels of BMIs, ranging from 86.7 to 87.8 years in women and 85.2 to 86.8 years in men. Conversely, subjects reporting slow walking pace had shorter life expectancies, being the lowest observed in slow walkers with a BMI less than 20 kg/m² (women: 72.4 years; men: 64.8 years). Smaller, less consistent differences in life expectancy were observed between participants with high and low handgrip strength, particularly in women. The same pattern of results was observed for waist circumference or body-fat percentage.ConclusionBrisk walkers were found to have longer life expectancies, which was constant across different levels and indices of adiposity. These findings could help clarify the relative importance of physical fitness and adiposity on mortality.     

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study

ObjectiveTo prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes.Patients and MethodsPatients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health–AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non–current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020.ResultsA total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses.ConclusionThe international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.     

Replacing Sedentary Behavior Time With Physical Activities,Recommended Physical Activity,and Incident Coronary Heart Disease

ObjectiveTo prospectively analyze the associations with coronary heart disease (CHD) risk of reallocating time from sedentary behavior to various physical activities using the isotemporal substitution model, particularly according to whether the participants meet the recommended physical activity level.MethodsWe included 455,298 UK Biobank participants free of CHD at baseline (March 13, 2006, to October 10, 2010). Sedentary behavior time was quantified by summing up the time spent on television watching, computer (not at work), and driving. Physical activities were categorized as daily-life activities (walking for pleasure, light do-it-yourself, and heavy do-it-yourself) and structured exercise (strenuous sports and other exercise).ResultsDuring a median follow-up of 11 years, 20,162 incident CHD cases were documented. Sedentary behavior time was significantly associated with a higher risk of CHD, independent of physical activity. Replacing 30 min/d of sedentary behavior with an equal time of various physical activities was associated with a 3% to 12% risk reduction of CHD. Replacing 1 h/d of sedentary behavior with different types of physical activities was associated with a 6% to 23% risk reduction of CHD. Sedentary behavior to strenuous sports reallocations showed the largest benefit. Reallocations of sedentary behavior to various physical activities showed particularly greater benefits among those who did not meet the physical activity recommendations.ConclusionsReplacing sedentary behavior time with various daily-life activities or structured exercise is associated with significant reductions in CHD risk.     

Ultrasound Imaging Offers Promising Alternative to Create 3-D Models for Personalised Auricular Implants

Three-dimensional imaging and advanced manufacturing are being applied in health care research to create novel diagnostic and surgical planning methods, as well as personalised treatments and implants. For ear reconstruction, where a cartilage-shaped implant is embedded underneath the skin to re-create shape and form, volumetric imaging and segmentation processing to capture patient anatomy are particularly challenging. Here, we introduce 3-D ultrasound (US) as an available option for imaging the external ear and underlying auricular cartilage structure, and compare it with computed tomography (CT) and magnetic resonance imaging (MRI) against micro-CT (µCT) as a high-resolution reference (gold standard). US images were segmented to create 3-D models of the auricular cartilage and compared against models generated from µCT to assess accuracy. We found that CT was significantly less accurate than the other methods (root mean square [RMS]: 1.30 ± 0.5 mm) and had the least contrast between tissues. There was no significant difference between MRI (RMS: 0.69 ± 0.2 mm) and US (0.55 ± 0.1 mm). US was also the least expensive imaging method at half the cost of MRI. These results unveil a novel use of ultrasound imaging that has not been presented before, as well as support its more widespread use in biofabrication as a low-cost imaging technique to create patient-specific 3D models and implants.     

Physical Activity and Mortality Across Levels of Adiposity: A Prospective Cohort Study From the UK Biobank

ObjectiveTo examine the combined and stratified associations of physical activity and adiposity measures, modelled as body mass index (BMI), abdominal adiposity (waist circumference), and body fat percentage (BF) with all-cause mortality.Patients and MethodsUsing the UK Biobank cohort, we extracted quintiles of self-reported weekly physical activity. Categories of measured BMI, waist circumference, and BF were generated. Joint associations between physical activity-adiposity categories and mortality were examined using Cox proportional hazards models adjusted for demographic, behavioral, and clinical covariates. Physical activity-mortality associations were also examined within adiposity strata. Participants were followed from baseline (2006 to 2010) through January 31, 2018.ResultsA total of 295,917 participants (median follow-up, 8.9 years, during which 6684 deaths occurred) were included. High physical activity was associated with lower risk of premature mortality in all strata of adiposity except for those with BMI ≥35 kg/m². Highest risk (HR, 1.54; 95% CI; 1.33 to 1.79) was observed in individuals with low physical activity and high BF as compared with the high physical activity–low BF referent. High physical activity attenuated the risk of high adiposity when using BF (HR, 1.24; 95% CI; 1.04 to 1.49), but the association was weaker with BMI (HR, 1.45; 95% CI; 1.21 to 1.73). Physical activity also attenuated the association between mortality and high waist circumference.ConclusionLow physical activity and adiposity were both associated with a higher risk of premature mortality, but high physical activity attenuated the increased risk with adiposity irrespective of adiposity metric, except in those with a BMI ≥35 kg/m².     

Nonlinear Associations Between Cumulative Dietary Risk Factors and Cardiovascular Diseases,Cancer, and All-Cause Mortality: A Prospective Cohort Study From UK Biobank

ObjectiveTo develop a score from cumulative dietary risk factors and examine its nonlinear associations with cardiovascular disease (CVD) and cancer incidence and mortality, as well as all-cause mortality.Patients and MethodsThere were 422,702 participants from UK Biobank included in this prospective study. Cumulative dietary risk factors were represented using a score ranging from 0 (healthiest) to 9 (least healthy). This was derived from 9 food items based on current UK guidelines using baseline data. Associations between the cumulative score and health outcomes were investigated using nonlinear penalized cubic splines fitted in Cox proportional hazard models. Follow-up was conducted until June 2020 for mortality, and for incidence, up to June 2020 in England and March 2017 in Wales and Scotland.ResultsThe median follow-up period was 9.0 years for incidence outcomes and 9.3 years for mortality outcomes. Each 1-point increment in the cumulative dietary risk factors score was associated with higher risk for incidence and mortality of the outcomes studied. The highest risks were identified for mortality due to heart failure (8.0% higher), CVD, and ischemic heart disease (both 7.0% higher). In addition, a higher diet score accounted for 18.8% of all deaths, 4.47% of incident cases of CVD, 25.5% of CVD deaths, 7.7% of incident cancers, and 18.2% of all cancer deaths.ConclusionOur findings show that dietary risk factors contributed to a large proportion of CVD and cancer events, as well as deaths, among those who did not meet most dietary recommendations.     

Design and Construction of a Low-Frequency Ultrasound Acquisition Device for 2-D Brain Imaging Using Full-Waveform Inversion

The main techniques used to image the brain and obtain structural data are magnetic resonance imaging and X-ray computed tomography. These techniques produce images with high spatial resolution, but with the disadvantage of requiring very large equipment with special installation needs. In addition, X-ray tomography uses ionizing radiation, which limits their use. Ultrasound imaging is a safe technology that is delivered using compact and mobile devices. However, conventional ultrasound reconstruction techniques have failed to obtain images of the brain because of, fundamentally, the presence of the skull and the distortion that it produces on ultrasound. Recent studies have indicated that full-waveform inversion, a computational technique originally from Earth science, has the potential to generate accurate 3-D images of the brain. This technology can overcome the limitations of conventional ultrasound imaging, but a prototype for transcranial applications does not yet exist. Here, we investigate different designs of an annular array of ultrasound transducers to optimize the number of elements and rotations needed to conduct transcranial imaging with full-waveform inversion. This device uses small-diameter, low-frequency transducers that readily propagate ultrasound through the skull with good signal-to-noise ratios. It also incorporates the use of rotations to produce a high-density coverage of the target and acquire redundant traces that are beneficial for full-waveform inversion. We have built a ring of 40 transducers to illustrate that this design is capable of reconstructing images of the brain, retrieving its anatomy and acoustic properties with millimeter resolution. Laboratory results reveal the ability of this device to successfully image a 2.5-D brain- and skull-mimicking phantom using full-waveform inversion. To our knowledge, this is the first prototype ever used for transcranial-like imaging. The importance of these findings and their implications for the design of a 3-D reconstruction system with possible clinical applications are discussed.     

Genetic Risk,Muscle Strength,and Incident Stroke: Findings From the UK Biobank Study

ObjectiveTo examine the associations of muscle strength and genetic risk for stroke with stroke incidence.Participants and MethodsWe included 284,767 white British participants of UK Biobank without genetic relatedness and stroke or myocardial infarction at baseline between March 13, 2006, and October 1, 2010. Genetic risk was assessed with polygenic risk scores, calculated by summing the risk-increasing alleles, weighted by the effect estimates. Muscle strength was assessed through grip strength tests by hand dynamometers. Incidence of overall (n= 4008), ischemic (n= 3031), and hemorrhagic (n=1073) stroke was adjudicated during 11.5-year follow-up.ResultsCompared with the bottom muscle strength tertile, hazard ratios (95% CI) of stroke were 0.81 (0.75 to 0.87) and 0.76 (0.71 to 0.82) for the middle and top muscle strength tertiles, respectively, after adjustment for confounders and genetic risk; higher genetic risk was independently associated with higher stroke incidence. Stroke hazards for the top muscle strength tertile were consistently lower across genetic risk strata, with no evidence of interaction. Compared with individuals with high muscle strength and low genetic risk, stroke hazards were higher for individuals who had medium or high genetic risk combined with low or medium muscle strength but not for those who had medium genetic risk but high muscle strength. Associations were similar for ischemic and hemorrhagic stroke (although CIs were inconclusive for some of the associations).ConclusionHigher muscle strength was associated with lower stroke incidence in all individuals, including those with high genetic susceptibility. The increased genetic risk of overall and ischemic stroke was partly attenuated through increased muscle strength.     

Night Shift Work,Genetic Risk,and Hypertension

ObjectiveTo perform a prospective cohort study to investigate whether night shift work is associated with incident hypertension and whether this association is modified by genetic susceptibility to hypertension because evidence on the association between night shift work and hypertension is insufficient.MethodsA total of 232,665 participants of UK Biobank who were recruited from 2006 to 2010 and observed to January 31, 2018, were included in this study. A Cox proportional hazards model with covariate adjustment was performed to assess the association between night shift work exposure and hypertension risk. We constructed a polygenic risk score (PRS) for genetic susceptibility to hypertension, which was used to explore whether genetic susceptibility to hypertension modified the effect of night shift work. The robustness of the results was assessed by sensitivity analysis.ResultsNight shift workers had a higher hypertension risk than day shift workers, which increased with increasing frequency of night shift work (P_trend<.001). The association was attenuated but still remained statistically significant in the fully adjusted model. We explored the joint effect of night shift work and genetic susceptibility on hypertension. Permanent night shift workers with higher hypertension PRSs had higher risk of hypertension than day workers with low PRSs.ConclusionNight shift work exposure was associated with increased hypertension risk, which was modified by the genetic risk for hypertension, indicating that there is a joint effect of night shift work and genetic risk on hypertension.     

Shift Work,Genetic Factors,and the Risk of Heart Failure: A Prospective Study of the UK Biobank

ObjectiveTo quantify the association of combined shift work and genetic factors with the incidence of heart failure (HF).Participants and MethodsThis study included 242,754 participants with complete shift work information in the UK Biobank. Participants were followed from baseline (2006 to 2010) through January 31, 2018. The association between shift work and HF incidence was investigated separately in males and females using a Cox proportional hazards model adjusted for covariates. In addition, we established a polygenic risk score and assessed whether shift work alters genetic susceptibility to HF.ResultsThe results showed a significant association of permanent night shift work with incident HF among females (hazard ratio, 2.25; 95% CI, 1.34 to 3.76; P=.002) after adjusting for age, and the association was attenuated in the fully adjusted model. Among men, we did not detect an association between shift work and HF. In addition, we observed that the association between the risk of HF and shift work was strengthened by high genetic risk. Permanent night shift work paired with high genetic risk, compared with low genetic risk, was suggested to be associated with the risk of HF in females (hazard ratio, 2.89; 95% CI, 1.05 to 7.94) but not in males.ConclusionShift work, particularly permanent night shift work, may increase the risk of HF in females, especially in those with high genetic risk.     

Adherence to a Healthy Sleep Pattern and Risk of Chronic Kidney Disease: The UK Biobank Study

ObjectiveTo examine the association of a healthy sleep pattern, characterized by sleep of 7 to 8 h/d, morning person, no insomnia, no frequent snoring, and no daytime sleepiness, with the risk of chronic kidney disease (CKD).MethodsWe included 392,218 European adults, aged 38 to 73 years, who were free of CKD at recruitment between March 13, 2006, and October 1, 2010, from the UK Biobank study. Data on sleep behaviors were collected through questionnaires at recruitment. Cox proportional hazards regression models were used to assess the relations between the healthy sleep score and risk of CKD.ResultsWe identified 18,842 incident CKD cases after a mean follow-up of 11.1 (SD 2.2) years. The healthy sleep score was inversely associated with the risk of CKD in a dose-dependent manner (P for trend, <.001). Compared with the participants with a poor sleep pattern (score of 0-1), the multivariate adjusted hazard ratio of CKD was 0.77 (95% CI, 0.71 to 0.84) for those with the healthiest sleep pattern (score of 5). In addition, we found that the inverse association was stronger in individuals without history of hypertension compared with individuals with hypertension at baseline (P for interaction, .003) and in those 60 years of age or younger compared with their older counterparts (P for interaction, <.001).ConclusionOur data suggest that adherence to an overall healthy sleep pattern is associated with a lower risk of CKD, especially for individuals without history of hypertension and those who are younger.     

Association of Timing and Balance of Physical Activity and Rest/Sleep With Risk of COVID-19: A UK Biobank Study

Behavioral lifestyle factors are associated with cardiometabolic disease and obesity, which are risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate whether physical activity, and the timing and balance of physical activity and sleep/rest, were associated with SARS-CoV-2 positivity and COVID-19 severity. Data from 91,248 UK Biobank participants with accelerometer data and complete covariate and linked COVID-19 data to July 19, 2020, were included. The risk of SARS-CoV-2 positivity and COVID-19 severity—in relation to overall physical activity, moderate-to-vigorous physical activity (MVPA), balance between activity and sleep/rest, and variability in timing of sleep/rest—was assessed with adjusted logistic regression. Of 207 individuals with a positive test result, 124 were classified as having a severe infection. Overall physical activity and MVPA were not associated with severe COVID-19, whereas a poor balance between activity and sleep/rest was (odds ratio [OR] per standard deviation: 0.71; 95% confidence interval [CI], 0.62 to 0.81]). This finding was related to higher daytime activity being associated with lower risk (OR, 0.75; 95% CI, 0.61 to 0.93) but higher movement during sleep/rest being associated with higher risk (OR, 1.26; 95% CI, 1.12 to 1.42) of severe infection. Greater variability in timing of sleep/rest was also associated with increased risk (OR, 1.21; 95% CI, 1.08 to 1.35). Results for testing positive were broadly consistent. In conclusion, these results highlight the importance of not just physical activity, but also quality sleep/rest and regular sleep/rest patterns, on risk of COVID-19. Our findings indicate the risk of COVID-19 was consistently approximately 1.2-fold greater per approximately 40-minute increase in variability in timing of proxy measures of sleep, indicative of irregular sleeping patterns.     

The Lifestyle-Related Cardiovascular Risk Is Modified by Sleep Patterns

ObjectiveTo prospectively assess whether sleep patterns modified lifestyle-associated cardiovascular disease (CVD) risk.Patients and MethodsThis study included 393,690 participants without CVD at baseline measurements between March 13, 2006, and October 1, 2010, from UK Biobank. A lifestyle score was calculated on the basis of the 4 lifestyle factors (smoking, alcohol consumption, physical activity, and diet), and sleep patterns were constructed based on sleep duration, chronotype, insomnia, snoring, and daytime dozing.ResultsDuring a median follow-up of 8.93 years, we observed 10,218 incident CVD events, including 6595 myocardial infarctions (MIs) and 3906 strokes. We found that sleep patterns significantly modified the relations of the lifestyle score with incident CVD (P for interaction =.007) and MI (P for interaction =.004). Among participants with a poor sleep pattern, unfavorable lifestyle (per score increase) was associated with 25% (95% CI, 13% to 39%) and 29% (95% CI, 13% to 47%) increased risks for CVD and MI, while among participants with a healthy sleep pattern, unfavorable lifestyle was associated with 18% (95% CI, 15% to 21%) and 17% (95% CI, 13% to 21%) increased risks for CVD and MI.ConclusionOur results indicate that adherence to a healthy sleep pattern may attenuate the CVD risk associated with an unfavorable lifestyle.     

Beyond Influenza Vaccination: Expanding Infrastructure for Hospital-based Pediatric COVID-19 Vaccine Delivery

Controlling the spread of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), will rely on vaccination at increasing rates and in an equitable manner. The main reasons for under-vaccination are varied among different segments of the population and include vaccine hesitancy and lack of access. While vaccine hesitancy is complicated and requires long-term solutions, access can be enhanced through evidence-based delivery strategies that augment conventional approaches. Hospital-based COVID-19 vaccination programs hold particular promise in reaching populations with decreased vaccine access and those at higher risk for adverse outcomes from SARS-CoV-2 infection. Hospitals have the necessary equipment and storage capabilities to maintain cold chain requirements—a common challenge in the primary care setting—and can serve as a central distribution point for delivering vaccines to patients in diverse hospital locations, including inpatient units, emergency departments, urgent care centers, perioperative areas, and subspecialty clinics. They also have the capacity for mass-vaccination programs and other targeted outreach efforts. Hospital-based programs that have been successful in implementing influenza and other routine vaccinations can leverage existing infrastructure, such as electronic health record–related tools. With the possibility of COVID-19 becoming endemic, much like seasonal influenza, these programs will require flexibility as well as planning for long-term sustainability. This commentary highlights existing vaccine delivery to children in hospital-based settings, including key advantages and important challenges, and outlines how these systems could be expanded to include the COVID-19 vaccine delivery.     

Osteoporosis and Its Association With Cardiovascular Disease,Respiratory Disease,and Cancer: Findings From the UK Biobank Prospective Cohort Study

ObjectiveTo investigate sex-specific associations of osteoporosis with incidence of and mortality from cardiovascular disease (CVD), respiratory disease, and cancer as well as with all-cause mortality.MethodsIn total, 305,072 participants (53% [161,383] women) of UK Biobank were included in this study (2007-2010). Self-reported diagnosis of osteoporosis at baseline was the exposure of interest. The outcomes were CVD, respiratory disease, chronic obstructive pulmonary disease (COPD), all cancer, and prostate and breast cancer incidence and mortality and all-cause mortality. Associations between osteoporosis and outcomes were investigated using Cox proportional hazards models.ResultsIn men, osteoporosis was associated with a higher incident risk of all respiratory diseases (hazard ratio [HR], 1.26; 95% CI, 1.06 to 1.50) including COPD (HR, 1.82; 95% CI, 1.38 to 2.40). Men with osteoporosis also had a higher mortality risk from all causes (HR, 1.71; 95% CI, 1.38 to 2.11), CVD (HR, 1.68; 95% CI, 1.19 to 2.37), respiratory disease (HR, 2.35; 95% CI, 1.70 to 3.24), and COPD (HR, 3.64; 95% CI, 2.24 to 5.91). These associations persisted after adjustment for age, body mass index, and comorbidities. Women with osteoporosis had a higher risk of incident CVD (HR, 1.24; 95% CI, 1.97 to 1.44), respiratory disease (HR, 1.23; 95% CI, 1.13 to 1.33), and COPD (HR, 1.29; 95% CI, 1.10 to 1.52). Women with osteoporosis also had a higher mortality risk from respiratory disease (HR, 1.31; 95% CI, 1.00 to 1.72) and breast cancer (HR, 1.60; 95% CI, 1.14 to 2.26).ConclusionCompared with women, men with osteoporosis had a higher risk of all-cause mortality, mortality from respiratory diseases including COPD, and cancer incidence. Osteoporosis was strongly associated with respiratory disease and COPD in both sexes, even after full adjustment for covariates, although men with osteoporosis experienced a higher risk of adverse outcomes.