Inverse Dose-response Association Research Articles

Association between weight loss and outcomes in patients undergoing atrial fibrillation ablation: a systematic review and dose–response meta-analysis

BackgroundObesity is an strong risk factor for atrial fibrillation (AF), and obesity can affect the prognosis of AF. However, the role of weight loss on outcomes after ablation remains unclear.ObjectivesThis study aims to determine the relationship between weight loss and outcomes in patients with AF ablation, as well as the potential dose–response relationship.MethodsThe Cochrane Library, PubMed, and Embase databases were searched to identify studies that reported a relationship between weight loss and ablation up to August 17, 2021. Relative risks (RRs) were pooled using random-effects models.ResultsOne randomized, open-labeled clinical trial and seven cohort studies involving 1283 patients were included. The mean body mass index of all included studies was over 30 kg/m2. The clinical trial showed a non-significant benefit of weight loss intervention on AF recurrence (Odd risk [OR] = 1.02, 95% confidence interval [CI] 0.70–1.47). Meta-analysis based on observational studies showed that the recurrence rate of AF after ablation was significantly reduced (RR = 0.43, 95% CI 0.22–0.81, I2 = 97%) in relatively obese patients with weight loss compared with the control group. Each 10% reduction in weight was associated with a decreased risk of AF recurrence after ablation (RR = 0.54, 95% CI 0.33–0.88) with high statistical heterogeneity (I2 = 76%). An inverse linear association (Pnon-linearity = 0.27) between AF relapse and increasing weight loss was found.ConclusionsOur results first suggest an inverse dose–response association between weight loss and risk of recurrent AF after ablation, with moderate certainty.Graphical

Association between the Oxidative Balance Score and Incident Chronic Kidney Disease in Adults

Oxidative stress is a novel risk factor for chronic kidney disease (CKD). The oxidative balance score (OBS) was developed to represent the overall oxidative balance based on dietary and lifestyle pro-oxidant and antioxidant components. The aim of this study is to verify the relationship between the OBS and the incidence of CKD. Data from 5795 participants without CKD at the baseline survey of the Korean Genome and Epidemiology Study were analyzed. Participants were classified into sex-specific OBS tertiles. During the mean follow-up period of 13.6 years, 286 men and 382 women newly developed CKD. The Cox proportional hazard spline curve revealed an inverse dose-response association between the OBS and incident CKD in both men and women. Multiple Cox proportional hazard regression analysis revealed that the adjusted hazard ratios (95% confidence intervals) for sex-specific highest (T3) and middle (T2) OBS tertile groups were 0.80 (0.59-1.08) and 0.70 (0.51-0.95), respectively, in men and 0.76 (0.59-0.98) and 0.73 (0.55-0.96), respectively, in women, with the sex-specific lowest OBS tertile group (T1) as the reference. These results suggest that a healthy diet and lifestyle that increases the OBS may help prevent CKD in both men and women.

Protective Effects of Lovastatin in a Population-Based ALS Study and Mouse Model.

The objective of this study was to use a novel combined pharmacoepidemiologic and amyotrophic lateral sclerosis (ALS) mouse model approach to identify potential motor neuron protective medications. We constructed a large, population-based case-control study to investigate motor neuron disease (MND) among US Medicare beneficiaries aged 66 to 90 in 2009. We included 1,128 incident MND cases and 56,400 age, sex, race, and ethnicity matched controls. We calculated MND relative risk for >1,000 active ingredients represented in Part D (pharmacy) claims in 2006 to 2007 (>1 year before diagnosis/reference). We then applied a comprehensive screening approach to select medications for testing in SOD1G93A mice: sulfasalazine, telmisartan, and lovastatin. We treated mice with the human dose equivalent of the medication or vehicle via subcutaneous osmotic pump before onset of weakness. We then assessed weight, gait, and survival. In additional mice, we conducted histological studies. We observed previously established medical associations for MND and an inverse dose-response association between lovastatin and MND, with 28% reduced risk at 40 mg/day. In SOD1G93A mouse studies, sulfasalazine and telmisartan conferred no benefit, whereas lovastatin treatment delayed onset and prolonged survival. Lovastatin treated mice also had less microgliosis, misfolded SOD1, and spinal motor neuron loss in the ventral horn. Lovastatin reduced the risk of ALS in humans, which was confirmed in an ALS mouse model by delayed symptom onset, prolonged survival, and preservation of motor neurons. Although further studies to understand the mechanism are required, lovastatin may represent a potential neuroprotective therapy for patients with ALS. These data demonstrate the utility of a combined pharmacoepidemiologic and mouse model approach. ANN NEUROL 2023;93:881-892.

Vitamin D and risk of hypertension among Black women.

Evidence of an association between plasma 25-hydroxyvitamin D [25(OH)D] levels and risk of hypertension, predominantly from studies of White individuals, suggests an inverse relationship. Limited data are available on Black individuals, who are more likely to have vitamin D deficiency. In the Black Women's Health Study (BWHS), a prospective study of 59 000 self-identified Black women from across the US, we assessed levels of a validated predicted vitamin D score in relation to incident hypertension. We followed 42 239 participants who were free of cardiovascular disease and cancer from 1995 to 2019, during which time 19 505 incident cases of hypertension were identified. Cox proportional hazards model were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of predicted vitamin D with the risk of incident hypertension. In age-adjusted analyses, there was a strong inverse dose-response association between predicted vitamin D score and hypertension risk, with an HR of .66 (95% CI: .63-.68, p trend<.0001) for the highest quartile of predicted vitamin D relative to the lowest. After control for potential confounders including body mass index, physical activity, and cigarette smoking, the HR was attenuated to .91 (95% CI: .87-.95, p trend=.002). In this prospective cohort study of Black women, predicted vitamin D score was weakly inversely associated with the incidence of hypertension. This observed association may reflect an inability to fully control for confounding factors.

Physical activity and diabetes mortality in people with type 2 diabetes: a prospective cohort study of 0.5 million US people

AimTo examine the association between physical activity and the cause of death with the greatest risk related to type 2 diabetes mellitus (T2DM) in a large population-based cohort representative of the general US adult population. MethodsA total of 41,726 adults suffering from T2DM (age 62 ± 14 years) and 459,660 adults without diabetes (age 46 ± 18 years) who participated in the National Health Interview Survey from 1997 to 2014 were included in this prospective cohort study. Self-reported moderate-to-vigorous physical activity (MVPA) was categorized into inactive, insufficiently active, active and very active. Mortality data was obtained from the National Death Index. Cox regression models adjusted for potential confounders were performed to estimate hazard ratio (HR) and 95% confidence interval (CI). ResultsDiabetes mortality cause showed the highest relative risk of death among adults with T2DM compared to adults without diabetes (HR 5.72 [3.15;10.39]). There was a non-linear inverse dose-response association between MVPA and diabetes mortality among adults with T2DM, up to a plateau in risk reduction at approximately 500 min/week. Any level of activity was inversely associated with a significantly lower risk of diabetes mortality compared with being inactive (insufficiently active HR 0.71[0.54;0.97], active HR 0.68 [0.49;0.95], very active HR 0.44 [0.32;0.60]). Compared to adults without diabetes, the risk of diabetes mortality decreased from HR 7.38 [4.00;13.58] for inactive people with T2DM to HR 3.34 [1.76;6.32] for very active people with T2DM. ConclusionsHigher levels of MVPA were associated with lower risk of diabetes mortality among adults with T2DM.

Longitudinal associations of serum survivin with the severity and prognosis of community-acquired pneumonia patients

BackgroundSurvivin is a member of apoptosis inhibitor proteins that evokes cellular proliferation and inhibits apoptosis. However, the role of survivin in community-acquired pneumonia (CAP) patients remains to be firmly established. The aim of this cohort study was to evaluate the correlations of serum survivin with the severity and prognosis of CAP patients. MethodsThis research included 470 eligible CAP patients. Serum fasting samples were drawn from patients, and serum survivin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, demographic characteristics and clinical information were collected. The prognosis of CAP patients was tracked. ResultsSerum survivin gradually decreased with elevated CAP severity scores. Additionally, the correlative analysis suggested that serum survivin was associated with many clinical characteristics. Furthermore, mixed linear and logistic regression models indicated that serum survivin was negatively associated with severity. After adjusting for confounding factors, logistic regression analyses found that lower serum survivin on admission elevated the risks of mechanical ventilation, vasoactive agent usage, longer hospital stays, ICU admission, and even death during hospitalization. Serum survivin in combination with CAP severity scores elevated the predictive capacities for severity and death in CAP patients compared with a single indicator. ConclusionOn admission, there are inverse dose-response associations of serum survivin with severity and poor prognosis in CAP patients, demonstrating that serum survivin may be involved in the pathophysiology process of CAP. Serum survivin may serve as a potential biomarker for disease evaluation and prognosis in CAP patients.

Vigorous physical activity, incident heart disease, and cancer: how little is enough?

Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity levels. There is a very limited understanding of the minimal and optimal amounts of vigorous physical activity in relation to mortality and disease incidence. A prospective study in 71 893 adults [median age (IQR): 62.5 years (55.3, 67.7); 55.9% female] from the UK Biobank cohort with wrist-worn accelerometry. VPA volume (min/week) and frequency of short VPA bouts (≤2 min) were measured. The dose-response associations of VPA volume and frequency with mortality [all-cause, cardiovascular disease (CVD) and cancer], and CVD and cancer incidence were examined after excluding events occurring in the first year. During a mean post-landmark point follow-up of 5.9 years (SD ± 0.8), the adjusted 5-year absolute mortality risk was 4.17% (95% confidence interval: 3.19%, 5.13%) for no VPA, 2.12% (1.81%, 2.44%) for >0 to <10 min, 1.78% (1.53%, 2.03%) for 10 to <30 min, 1.47% (1.21%, 1.73%) for 30 to <60 min, and 1.10% (0.84%, 1.36%) for ≥60 min. The 'optimal dose' (nadir of the curve) was 53.6 (50.5, 56.7) min/week [hazard ratio (HR): 0.64 (0.54, 0.77)] relative to the 5th percentile reference (2.2 min/week). There was an inverse linear dose-response association of VPA with CVD mortality. The 'minimal' volume dose (50% of the optimal dose) was ∼15 (14.3, 16.3) min/week for all-cause [HR: 0.82 (0.75, 0.89)] and cancer [HR: 0.84 (0.74, 0.95)] mortality, and 19.2 (16.5, 21.9) min/week [HR: 0.60 (0.50, 0.72)] for CVD mortality. These associations were consistent for CVD and cancer incidence. There was an inverse linear association between VPA frequency and CVD mortality. 27 (24, 30) bouts/week was associated with the lowest all-cause mortality [HR: 0.73 (0.62, 0.87)]. VPA of 15-20 min/week were associated with a 16-40% lower mortality HR, with further decreases up to 50-57 min/week. These findings suggest reduced health risks may be attainable through relatively modest amounts of VPA accrued in short bouts across the week.

Intake of legumes and cardiovascular disease: A systematic review and dose–response meta-analysis

AimsTo summarize the evidence on the association between the intake of legumes and the risk of cardiovascular disease (CVD) overall, coronary heart disease (CHD) and stroke, and to identify optimal intake levels for reduced disease risk through a systematic review and dose–response meta-analysis. Data synthesisWe have systematically searched PubMed, Scopus and Web of Science up to March, 2022 for the retrieval of intervention and observational studies (PROSPERO Reg. number: CRD42021247565). Pooled relative risks (RRs) comparing extreme categories of intake were computed using random-effects models. One-stage dose–response meta-analyses were also performed using random-effects models. 22 831 articles were screened resulting in 26 eligible observational studies (21 prospective cohort and 5 case–control studies). When comparing extreme categories of intake, the consumption of legumes was inversely associated with CVD (n = 25: RR = 0.94; 95%CI:0.89,0.99) and CHD (n = 16: RR = 0.90; 95%CI:0.85,0.96), but not with stroke (n = 9: RR = 1.00; 95%CI:0.93,1.08). We further found evidence for an inverse dose–response association with CHD, increasing in magnitude up to an intake of 400 g/week, after which the benefit seems to level-off. ConclusionsThe intake of legumes was associated with a reduced risk of CVD and CHD, but not with stroke, among individuals with the highest consumption levels. An intake level of 400 g/week seemed to provide the optimal cardiovascular benefit. Further research is needed to better understand the role of legumes in stroke subtypes.

Initial BMI and Weight Loss over Time Predict Mortality in Parkinson Disease.

Although weight loss is a frequent symptom in Parkinson disease (PD), there have been few studies on the association between body mass index (BMI) and mortality. The objective of this study was to investigate the association between BMI and change in BMI at diagnosis in patients with PD and all-cause mortality. Cohort study using Korean National Health Insurance Service-Elderly Cohort data. Patients with new-onset PD were selected using the International Classification of Diseases 10th edition code (G20). Then, patients who were diagnosed more than 3 times with PD and had been prescribed anti-parkinsonian medication for ≥30days were included. Those with a combined diagnosis of atypical parkinsonism and secondary parkinsonism were excluded. The primary outcome was all-cause mortality. Anthropometric data, including height and weight, were obtained from the health screening data to calculate BMI. The Cox proportional hazards model was used to assess mortality risk by BMI. Among the 2703 patients with PD, 492 (18.20%) died during the 11-year follow-up period. There was a significant inverse dose-response relationship between baseline BMI and mortality [<18.5kg/m2: hazard ratio (HR), 1.872, 95% CI, 1.338-2.494; 23-25kg/m2: HR, 0.695, 95% CI, 0.546-0.886; 25-30kg/m2: HR, 0.644, 95% CI, 0.476-0.869; ≥30kg/m2: HR, 0.396, 95% CI, 0.165-0.950]. Change in BMI of 10% revealed a significant association with mortality. Subgroup analyses by sex showed a significant inverse dose-response relationship between BMI and all-cause mortality only in women. We demonstrated an inverse dose-response association between BMI at diagnosis and mortality in patients with PD, especially in women. Early detection of PD before weight loss progression and proper management might improve mortality. The small number of obese PD participants in our study should be considered when interpreting and generalizing results.

Longitudinal Adherence to Diabetes Quality Indicators and Cardiac Disease: A Nationwide Population-Based Historical Cohort Study of Patients With Pharmacologically Treated Diabetes.

Background Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population-based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006-2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011-2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person-years of follow-up, 19 246 patients experienced cardiac disease. An inverse dose-response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients (<65 years). Low adherence to low-density lipoprotein cholesterol testing (≤2 years) during the first 5 years was associated with 41% increased risk of cardiac morbidity among younger patients. Patients who had uncontrolled low-density lipoprotein cholesterol in all first 5 years had hazard ratios of 1.60 (95% CI, 1.49-1.72) and 1.23 (95% CI, 1.14-1.32), among patients aged <65 and ≥65 years, respectively, compared with those who achieved target level. Patients who failed to achieve target levels of glycated hemoglobin or blood pressure had an increased risk (hazard ratios, 1.50-1.69) for cardiac outcomes. Conclusions Longitudinal adherence to quality indicators in diabetes care is associated with reduced risk of cardiac morbidity. Implementation of programs that measure and enhance quality of care may improve the health outcomes of people with diabetes.

Consistent pattern between physical activity measures and chronic pain levels: the Tromsø Study 2015 to 2016.

Epidemiological literature on the relationship between physical activity and chronic pain is scarce and inconsistent. Hence, our aim was to assess the relationship applying comprehensive methodology, including self-reported and accelerometer measures of physical activity and different severity levels of chronic pain. We used data from the Tromsø Study (2015-2016). All residents in the municipality, aged 40 years and older were invited to participate (n = 32,591, 51% women). A total of 21,083 (53%) women reported on questionnaires. Additionally, 6778 participants (54% women) were invited to wear accelerometers (6125 with complete measurements). Our exposure measures were self-reported leisure time physical activity, exercise frequency, duration, and intensity and 2 accelerometer measures (steps per day and minutes of moderate to vigorous physical activity per day). Outcome measurements were chronic pain and moderate-to-severe chronic pain. We used Poisson regression to estimate chronic pain prevalence and prevalence ratios for each physical activity measure, with adjustments for sex, age, education level, smoking history, and occupational physical activity. Our main analyses showed an inverse dose-response relationship between all physical activity measures and both severity measures of chronic pain, except that the dose-response relationship with exercise duration was only found for moderate-to-severe pain. All findings were stronger for the moderate-to-severe pain outcomes than for chronic pain. Robustness analyses gave similar results as the main analyses. We conclude that an inverse dose-response association between physical activity and chronic pain is consistent across measures. To summarize, higher levels of physical activity is associated with less chronic pain and moderate-to-severe chronic pain.

Associations of handgrip strength with all-cause and cancer mortality in older adults: a prospective cohort study in 28 countries.

Backgroundmixed evidence exists on the association between muscle strength and mortality in older adults, in particular for cancer mortality.Aimto examine the dose–response association of objectively handgrip strength with all-cause and cancer mortality.Study Design and Settingdata from consecutive waves from the Survey of Health, Ageing and Retirement in Europe comprising 27 European countries and Israel were retrieved. Overall, 54,807 men (45.2%; 128,753 observations) and 66,576 women (54.8%; 159,591 observations) aged 64.0 (SD 9.6) and 63.9 (SD 10.2) years, respectively, were included. Cox regression and Fine-Grey sub-distribution method were conducted.Resultsduring the follow-up period (896,836 person-year), the fully adjusted model showed the lowest significant risk estimates for the highest third of handgrip strength when compared with the first third (reference) in men (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.34–0.50) and women (HR, 0.38; 95% CI, 0.30–0.49) for all-cause mortality. We identified a maximal threshold for reducing the risk of all-cause mortality for men (42 kg) and women (25 kg), as well as a linear dose–response association in participants aged 65 or over. No robust association for cancer mortality was observed.Conclusionthese results indicate an inverse dose–response association between incremental levels of handgrip and all-cause mortality in older adults up to 42 kg for men and 25 kg for women, and a full linear association for participants aged 65 years or over. These findings warrant preventive strategies for older adults with low levels of handgrip strength.

Association Between Physical Activity and Risk of Depression

Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and depression is uncertain. To systematically review and meta-analyze the dose-response association between physical activity and incident depression from published prospective studies of adults. PubMed, SCOPUS, Web of Science, PsycINFO, and the reference lists of systematic reviews retrieved by a systematic search up to December 11, 2020, with no language limits. The date of the search was November 12, 2020. We included prospective cohort studies reporting physical activity at 3 or more exposure levels and risk estimates for depression with 3000 or more adults and 3 years or longer of follow-up. Data extraction was completed independently by 2 extractors and cross-checked for errors. A 2-stage random-effects dose-response meta-analysis was used to synthesize data. Study-specific associations were estimated using generalized least-squares regression and the pooled association was estimated by combining the study-specific coefficients using restricted maximum likelihood. The outcome of interest was depression, including (1) presence of major depressive disorder indicated by self-report of physician diagnosis, registry data, or diagnostic interviews and (2) elevated depressive symptoms established using validated cutoffs for a depressive screening instrument. Fifteen studies comprising 191 130 participants and 2 110 588 person-years were included. An inverse curvilinear dose-response association between physical activity and depression was observed, with steeper association gradients at lower activity volumes; heterogeneity was large and significant (I2 = 74%; P < .001). Relative to adults not reporting any activity, those accumulating half the recommended volume of physical activity (4.4 marginal metabolic equivalent task hours per week [mMET-h/wk]) had 18% (95% CI, 13%-23%) lower risk of depression. Adults accumulating the recommended volume of 8.8 mMET hours per week had 25% (95% CI, 18%-32%) lower risk with diminishing potential benefits and higher uncertainty observed beyond that exposure level. There were diminishing additional potential benefits and greater uncertainty at higher volumes of physical activity. Based on an estimate of exposure prevalences among included cohorts, if less active adults had achieved the current physical activity recommendations, 11.5% (95% CI, 7.7%-15.4%) of depression cases could have been prevented. This systematic review and meta-analysis of associations between physical activity and depression suggests significant mental health benefits from being physically active, even at levels below the public health recommendations. Health practitioners should therefore encourage any increase in physical activity to improve mental health.

Healthy lifestyle and the risk of conventional adenomas and serrated polyps: Findings from a large colonoscopy screening population.

Evidence on the link between healthy lifestyle and colorectal cancer (CRC) precursors is limited. Our study aimed to examine and compare the associations of healthy lifestyle with CRC precursors in adenoma (AD)-carcinoma and serrated pathways. A total of 24 480 participants including 6309 ADs, 1343 serrated polyps (SPs), and 16 828 polyp-free controls were included. A healthy lifestyle score (HLS) was constructed based on five lifestyle factors including cigarette smoking, alcohol drinking, physical activity, diet and body weight, and categorized into least, slightly, moderately and most healthy. Multivariable logistic regressions were used to estimate odds ratio (OR) and 95% confidence interval (CI). Inverse dose-response associations between the HLS and risk of ADs were observed (OR per 1 score increment for ADs: 0.82 [95% CI 0.79-0.84]; for SPs: 0.73 [95% CI 0.69-0.78]), and the association with SPs was more evident than with ADs (OR 0.90, 95% CI 0.85-0.96). Compared to participants with the least healthy lifestyle, those with the most healthy lifestyle had 47% lower risk of ADs (OR 0.53, 95% CI 0.47-0.59) and 70% lower risk of SPs (OR 0.30, 95% CI 0.23-0.39), respectively. These inverse associations were consistent across lesion stage and anatomic subsite and not modified by any stratification factors. The risk advancement periods for the most vs the least healthy lifestyle were -9.49 years for ADs and -20.69 years for SPs. Our findings help confirm the preventive role of healthy lifestyle in colorectal carcinogenesis.

Plasma 25-hydroxyvitamin D3 concentrations and incident risk of ischemic stroke in rural Chinese adults: New insight on ceiling effect

ObjectiveThe aim of this study was to investigate the relationship between 25-hydroxyvitamin D3 (25[OH]D3) and ischemic stroke and its potential modifying factors in rural Chinese adults. MethodsThis nested case-control study was drawn from the H-type Hypertension and Stroke Prevention and Control Project, a community-based, prospective, observational study. Plasma 25(OH)D3 was measured by liquid chromatography with tandem quadrupole mass spectrometry. All stroke records came from the Chinese Center for Disease Control and Prevention. Multiple logistic regression models were used to evaluate the association between 25(OH)D3 and risk of ischemic stroke. ResultsWe included 1079 participants with ischemic stroke and 1079 matched controls. Due to a non-linear relationship, the analyses were stratified by 25(OH)D3. For those with 25(OH)D3 < 20 ng/mL, there was a 15% reduction in the risk of ischemic stroke for each SD increment in 25(OH)D3 (odds ratio, 0.85; 95% confidence interval, 0.73–0.99). Compared with the lowest-tertile group, the risk of ischemic stroke decreased by 39% (odds ratio, 0.61; 95% confidence interval, 0.41–0.89) in the highest-tertile group. Furthermore, two effect modifiers were identified: diabetes and homocysteine level. Although participants with 25(OH)D3 ≥ 20 ng/mL had the lowest risk of ischemic stroke overall, there was no dose-response association within that range. ConclusionsAn inverse dose-response association between 25(OH)D3 and incident risk of ischemic stroke in rural Chinese adults was only observed in those with 25(OH)D3 < 20 ng/mL, along with two effect modifiers. Higher levels of 25(OH)D3 did not confer additional benefit.

Cardiorespiratory fitness and mortality from all causes, cardiovascular disease and cancer: dose–response meta-analysis of cohort studies

ObjectiveCurrent evidence of the associations between cardiorespiratory fitness (CRF) and mortality is limited. We performed a meta-analysis to assess the dose–response association of CRF with mortality from all causes, cardiovascular...

Association of Physical Activity, Including Amount and Maintenance, With All-Cause Mortality in Parkinson Disease

The protective effects of physical activity (PA) against Parkinson disease (PD) development have been suggested; however, the association of PA with mortality in PD has rarely been investigated. To evaluate the association between PA and mortality in individuals with PD and determine how the amount and maintenance of PA are associated with mortality. This nationwide population-based cohort study used Korean National Health Insurance System data. Participants were included from January 1, 2010, and December 31, 2013, and were followed up until December 31, 2017. Data were analyzed from September 2020 to March 2021. Individuals who were newly diagnosed with PD were selected using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code G20 and registration code V124 in the program for rare intractable diseases in 2010 through 2013. Individuals who underwent health checkups within 2 years before and after the PD diagnosis were enrolled. Those aged younger than 40 years or with missing data were excluded. Physical activity levels were collected using self-reported questionnaires. All-cause mortality. A total of 45 923 individuals were identified; 10 987 were enrolled, and 34 individuals younger than 40 years and 254 with missing data were excluded. A total of 10 699 individuals with PD were included; 4925 (46%) were male and 5774 (54%) were female, and the mean (SD) age was 69.2 (8.8) years. During the 8-year follow-up period, there were 1823 deaths (17%). The mortality rate was lower among individuals who were physically active vs inactive at all PA intensities (vigorous: hazard ratio [HR], 0.80 [95% CI, 0.69-0.93]; moderate: HR, 0.66 [95% CI, 0.55-0.78]; light: HR, 0.81 [95% CI, 0.73-0.90]). There was a significant inverse dose-response association between the total amount of PA and mortality (HRs: vigorous, 0.80 [95% CI, 0.69-0.93]; moderate, 0.66 [95% CI, 0.55-0.78]; light, 0.81 [95% CI, 0.73-0.90]; P < .001). Moreover, maintenance of PA was associated with the mortality rate. Individuals with PD who were physically active both before and after the PD diagnosis had the greatest reduction in mortality rate across all PA intensities (HRs: vigorous, 0.66 [95% CI, 0.50-0.88]; moderate, 0.49 [95% CI, 0.32-0.75]; light, 0.76 [95% CI, 0.66-0.89]). Individuals who started PA after receiving the PD diagnosis had a lower mortality rate than those who remained physically inactive (HRs: vigorous, 0.82 [95% CI, 0.70-0.97]; moderate, 0.69 [95% CI, 0.57-0.83]; light, 0.86 [95% CI, 0.78-0.98]). This analysis found a dose-response association between PA and all-cause mortality in PD. Reverse causality may exist, and future prospective randomized clinical trials are warranted to determine the effect of PA on mortality in PD.

Dose–response relationships of accelerometer‐measured sedentary behaviour and physical activity with non‐alcoholic fatty liver disease

Although a few studies have confirmed the association of accelerometer-measured sedentary behaviour (SB) and physical activity (PA) with non-alcoholic fatty liver disease (NAFLD), PA intensity and co-dependent daily time-use of movement behaviours are yet to be studied. To cross-sectionally examine the dose-response relationship between accelerometer-measured SB or PA and NAFLD using cubic spline analysis and the interdependence of movement behaviours over 24hours with compositional data analysis. Data were obtained between May 2017 and February 2020 from 1914 people who were not heavy alcohol drinkers using health check-ups at the Meiji Yasuda Shinjuku Medical Center, Tokyo. SB, light-intensity PA (LPA) and moderate- to vigorous-intensity PA (MVPA) were evaluated using a triaxial accelerometer. Fatty liver was diagnosed by ultrasonography. A multivariable-adjusted logistic model showed an inverse association between MVPA and NAFLD (odds ratio [OR] per 600 metabolic equivalents [MET]-min/week=0.85, 95% confidence interval [CI]=0.76-0.96). MVPA showed rapidly decreasing odds of NAFLD to approximately 1800 MET-min/week in cubic spline analysis and then a moderate decline. Although SB was significantly associated with NAFLD in a body mass index (BMI)-unadjusted model, it was not significant in a BMI-adjusted model. In the compositional isotemporal substitution, reallocating 60min/day of SB to MVPA decreased the odds of NAFLD by 22% (OR=0.78, 95% CI: 0.65-0.93), whereas reallocating 60min/day of MVPA to SB increased it by 69% (OR=1.69, 95% CI: 1.12-2.38). The inverse dose-response association between MVPA and NAFLD confirms increased MVPA as a target for the prevention of NAFLD.

Association Between Risk of COVID-19 Infection in Nonimmune Individuals and COVID-19 Immunity in Their Family Members

The association between COVID-19 immunity within families and the risk of infection in nonimmune family members is unknown. To investigate the association between risk of COVID-19 in nonimmune individuals and the number of their family members with known immunity acquired from a previous COVID-19 infection or full vaccination (2 vaccine doses). In this cohort study of data from nationwide registries in Sweden, all individuals who acquired immunity from either previous COVID-19 infection or full vaccination until May 26, 2021, were considered for inclusion. Each person with immunity was matched 1:1 to an individual without immunity from an identified cohort of individuals with families comprising 2 to 5 members. Number of immune family members in each family on April 14, 2021 (index date), who acquired immunity from a previous COVID-19 infection or full vaccination (2 doses of the mRNA-1273, BNT162b2 mRNA, or ChAdOx1 nCoV-19 vaccine). Incident COVID-19 infection in nonimmune family members from April 15 to May 26, 2021. A total of 1 789 728 individuals from 814 806 families were included in the analysis. Each family comprised 2 to 5 family members, with a mean (SD) age at baseline of 51.3 (19.5) years. During a mean (range) follow-up time of 26.3 (1-40) days, 88 797 of 1 549 989 (5.7%) nonimmune family members (mean [SD] age, 51.6 [17.7] years; 790 276 men [51.0%]) were diagnosed with COVID-19. There was an inverse dose-response association between the number of immune members in each family and the risk of incident COVID-19 infection in nonimmune family members. Nonimmune families with 1 immune family member had a 45% to 61% lower risk of contracting COVID-19 (hazard ratio [HR], 0.39-0.55; 95% CI, 0.37-0.61, P < .001). The risk reduction increased to 75% to 86% in families with 2 immune family members (HR, 0.14-0.25; 95% CI, 0.11-0.27; P < .001), 91% to 94% with 3 immune family members (HR, 0.06-0.09; 95% CI, 0.04-0.10; P < .001), and 97% with 4 immune family members (HR, 0.03; 95% CI, 0.02-0.05; P < .001). The results were similar for the outcome of COVID-19 infection that was severe enough to warrant a hospital stay. In this cohort study, family members without immunity had a 45% to 97% lower risk of contracting COVID-19 as the number of immune family members increased. Vaccination is a key strategy for decreasing the transmission of the virus within families.

Associations between Device-measured Physical Activity and Cardiometabolic Health in the Transition to Early Adulthood.

The aims of this study were to investigate the cross-sectional and prospective associations between accelerometer-measured physical activity and cardiometabolic health in the transition to adulthood. Data from the 1993 Pelotas (Brazil) Birth Cohort were analyzed (n = 2280). Moderate-to-vigorous intensity physical activity (MVPA) (measured using a triaxial accelerometer) and cardiometabolic health (total fat mass, blood glucose, non-high-density lipoprotein cholesterol, triglycerides, and mean resting blood pressure) were examined at age 18 and 22 yr. Overall, inverse dose-response associations between MVPA and cardiometabolic health at age 18 and 22 yr were observed in cross-sectional analyses of data from men and women. Prospective analyses showed that, in general, MVPA declined, and cardiometabolic health worsened in this 4-yr period in both men and women. Cardiometabolic health at age 22 yr reflected both MVPA at age 18 yr (β, -0.007; 95% confidence interval [CI], -0.014 to 0.000) and changes in MVPA from 18 to 22 yr (β, -0.030; 95% CI, -0.043 to -0.016) in men, but only changes in MVPA in women (β, -0.035; 95% CI, -0.058 to -0.011). In analyses of change over time, men who improved MVPA by 20 to 30 min·d-1 showed significant improvements in cardiometabolic health over 4 yr. The magnitude of association was slightly stronger for MVPA in 10-min bouts than for MVPA accumulated in bouts of 1 min, especially in women. Moderate-to-vigorous intensity physical activity is an important predictor of cardiometabolic health in early adulthood. Strategies to prevent declines in MVPA at this life stage are required to prevent deteriorating cardiometabolic health profiles.