Abstract P146: Serum Magnesium and Mortality in the General US Population: Results From the NHANES I Epidemiologic Follow-up Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Xi Zhang ◽  
Jin Xia ◽  
Liana C. Del Gobbo ◽  
Adela Hruby ◽  
Ka He ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
Serum Magnesium ◽  
Cox Proportional Hazards ◽  
Follow Up Study ◽  
Normal Reference ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Low Serum

Introduction: Low magnesium (Mg) intake and/or status has been associated with increased risk of chronic disease, including cardiovascular disease (CVD) and cancer. However, whether and to what extent low serum Mg levels are associated with all-cause or cause-specific mortality in the general population is uncertain. Hypothesis: We aimed to quantify the dose-response associations between low concentrations of serum Mg and mortality from all causes, cancer, CVD, and stroke in the general US population. Methods: We analyzed prospective data on 14,353 participants aged 25-74 years with baseline measures of serum Mg concentrations from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study 1971-2006. We estimated the mortality hazard ratios (HRs) for participants within predefined and clinically meaningful categories of serum Mg levels, including <0.7, 0.7-0.74, 0.75-0.79, 0.8-0.9 (normal reference), 0.9-0.94, 0.95-0.99, and ≥1.0 mmol/L, using Cox proportional hazards models. Restricted cubic spline models were applied to examine potentially nonlinear relationships between serum Mg and mortality. Results: During a mean follow-up of 27.6 years, 7,072 deaths occurred, 3,310 (47%) CVD deaths, 1,533 (22%) cancer deaths, and 281 (4%) stroke deaths. Twenty-one percent of all participants had low levels of serum Mg (<0.8 mmol/L) and 1.5% had extremely low serum Mg (<0.7 mmol/L). Age-adjusted all-cause mortality rates were 3845, 3491, 3471, 3400 (normal reference), 3531, 3525, and 3836 per 100,000 person-years for increasing categories of serum Mg; the HRs and 95% confidence intervals for increasing serum Mg were 1.32 (1.02-1.72), 0.93 (0.74-1.16), and 1.06 (0.96-1.18), 1.07 (0.97-1.18), 0.94 (0.77-1.13), and 0.93 (0.72-1.21), compared to the reference group (0.8-0.9 mmol/L). An L-shaped association between serum Mg concentrations and all-cause mortality was observed after adjusting for potential confounders (Figure). No statistically significant associations were observed between serum Mg and cancer, CVD, or stroke mortality. Conclusions: Very low serum Mg levels were significantly associated with all-cause mortality in the general US population. Our findings support the hypothesis that Mg deficiency as defined by very low serum Mg may have an important influence on mortality.

Abstract P009: Risk of Mortality According to Burden of Atrial Fibrillation: Results From a 60-year Cohort Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
William F McIntyre ◽  
Mahmoud Tourabi ◽  
Philip D St John ◽  
Robert B Tate
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Events ◽  
Sinus Rhythm ◽  
Proportional Hazards ◽  
Anticoagulation Therapy ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality

Introduction: Atrial Fibrillation (AF) is the most common serious cardiac arrhythmia and is associated with an increased risk of stroke and mortality. These risks can be modified with oral anticoagulation therapy. Clinically, the arrhythmia can be permanent or intermittent. Prior studies that have used time-constant, categorical covariates to examine the relationship between the pattern of AF and the occurrence of adverse events have produced conflicting results. We hypothesized that the amount of time that patients spend in AF, hereinafter termed arrhythmia “burden”, may be important in predicting adverse events. Objective: To examine the effects of the burden of AF on all-cause mortality. Methods: The Manitoba Follow-Up Study is a longitudinal, prospective study of 3983 originally healthy young men (mean age at entry 30 years) who have been followed with routine medical and electrocardiographic examinations since 1948. After 60 years of follow-up to July 1, 2008, AF had been documented on the electrocardiograms of 581 men (15% of the cohort) and 3182 (80%) of the original cohort had died. We created a Cox proportional hazards model with time-dependent covariates to estimate relative risks for mortality according to AF burden. AF status during each follow-up visit was classified as persistent when the patient was in AF on consecutive examinations, transient when the patient reverted to sinus rhythm after being in AF and incident when the patient developed AF after a period in sinus rhythm. Results: Results of the Cox proportional hazards regression model are displayed in the Table. Age, persistent AF and incident AF were all significant variables in the model. Holding all the other variables constant, persistent AF increased the risk of death by two times and incident AF increased the risk of death by 87%. Conclusions: Persistent AF and incident AF are associated with increased all-cause mortality. Estimating AF burden may have implications for risk stratification in patients with AF.

Increased risk of stroke after trigeminal neuralgia – a population-based follow-up study

Cephalalgia ◽  
2011 ◽  
Vol 31 (8) ◽  
pp. 937-942 ◽  
Author(s):  
Shin-Liang Pan ◽  
Li-Sheng Chen ◽  
Ming-Fang Yen ◽  
Yueh-Hsia Chiu ◽  
Hsiu-Hsi Chen
Keyword(s):  
Trigeminal Neuralgia ◽  
Proportional Hazards ◽  
Underlying Mechanism ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Follow Up Study ◽  
Medical Disorders ◽  
Increased Risk

Background: There are no reports on the risk of stroke after trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether the occurrence of TN is associated with a higher risk of developing stroke. Methods: A total of 1453 people with at least three ambulatory visits in 2001 with the principal diagnosis of TN were enrolled in the TN cohort. The non-TN cohort consisted of 5812 age- and sex-matched, randomly sampled subjects without TN. The 2-year stroke-free survival rate between the two groups was compared using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of stroke after adjustment for demographic and clinical covariates. Results: In the TN cohort, 73 patients developed stroke during follow-up, while in the non-TN cohort, 157 subjects suffered a stroke. The crude hazard ratio of stroke for the subjects with TN was 1.86 (95% CI, 1.41–2.45; p < 0.0001). The adjusted hazard ratio was 1.76 (95% CI, 1.33–2.33; p < 0.0001) after adjusting for demographic characteristics and comorbid medical disorders. Conclusion: This study showed a significantly increased risk of developing stroke after TN. Further studies are needed to investigate the underlying mechanism of this association.

Faster Transport Status and Mortality in Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

2015 ◽  
Vol 40 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Liping Xiong ◽  
Li Fan ◽  
Qingdong Xu ◽  
Qian Zhou ◽  
Huiyan Li ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
All Cause Mortality ◽  
History Of ◽  
The Relationship

Background: There are limited data regarding the relationship between transport status and mortality in anuric continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: According to the dialysate to plasma creatinine ratio (D/P Cr), 292 anuric CAPD patients were stratified to faster (D/P Cr ≥0.65) and slower transport groups (D/P Cr <0.65). The Cox proportional hazards models were used to evaluate the association of transport status with mortality. Results: During a median follow-up of 22.1 months, 24% patients died, 61.4% of them due to cardiovascular disease (CVD). Anuric patients with faster transport were associated with an increased risk of all-cause mortality (HR (95% CI) = 2.16 (1.09-4.26)), but not cardiovascular mortality, after adjustment for confounders. Faster transporters with pre-existing CVD had a greater risk for death compared to those without any history of CVD. Conclusion: Faster transporters were independently associated with high all-cause mortality in anuric CAPD patients. This association was strengthened in patients with pre-existing CVD.

scholarly journals Risk of Subsequent Malignant Neoplasms in Long-Term Hereditary Retinoblastoma Survivors After Chemotherapy and Radiotherapy

2014 ◽  
Vol 32 (29) ◽  
pp. 3284-3290 ◽  
Author(s):  
Jeannette R. Wong ◽  
Lindsay M. Morton ◽  
Margaret A. Tucker ◽  
David H. Abramson ◽  
Johanna M. Seddon ◽  
...  
Keyword(s):  
Regression Models ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Malignant Neoplasms ◽  
Follow Up Study ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
Long Term Follow Up

Purpose Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks. Patients and Methods In a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale. Results Nearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) –containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio [HR], 1.27; 95% CI, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% CI, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% CI, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% CI, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% CI, 1.76 to 15.17) but not for those receiving AAs at age ≥ 1 year (HR, 1.75; 95% CI, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P = .01). Conclusion This comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

scholarly journals Association of oral contraceptives and tubal ligation with risk of early natural menopause

2021 ◽  
Author(s):  
C R Langton ◽  
B W Whitcomb ◽  
A C Purdue-Smithe ◽  
L L Sievert ◽  
S E Hankinson ◽  
...  
Keyword(s):  
Oral Contraceptives ◽  
Proportional Hazards ◽  
Reproductive Factors ◽  
Cox Proportional Hazards ◽  
Tubal Ligation ◽  
Health Study ◽  
Early Menopause ◽  
Natural Menopause ◽  
Increased Risk

Abstract STUDY QUESTION What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S) The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A

Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis

2021 ◽  
pp. 1-11
Author(s):  
Dongying Fu ◽  
Jiani Shen ◽  
Wei Li ◽  
Yating Wang ◽  
Zhong Zhong ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Proportional Hazards ◽  
Elevated Serum ◽  
Ultra Performance Liquid Chromatography ◽  
Cox Proportional Hazards ◽  
Serum Samples ◽  
Entire Cohort ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Male Patients

Background: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. Methods: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. Results: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8–61.0) μM. During a median follow-up of 63.7 months (IQR, 43.9–87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01–1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07–1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02–1.94; p = 0.038) in men but not in women. Conclusions: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.

Abstract P169: Health Literacy and Outcomes in Heart Failure: a Prospective Community Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Matteo Fabbri ◽  
Kathleen Yost ◽  
Lila Finney Rutten ◽  
Sheila Manemann ◽  
Susan Weston ◽  
...  
Keyword(s):  
Heart Failure ◽  
Health Literacy ◽  
Proportional Hazards ◽  
International Classification Of Diseases ◽  
Cox Proportional Hazards ◽  
Low Literacy ◽  
Adequate Health Literacy ◽  
Low Health Literacy ◽  
Increased Risk

Background: Growing evidence documents the association between low health literacy and poorer health outcomes. However, less is known about the relationship between health literacy and outcomes among patients with heart failure (HF). We examined the association of health literacy with risk of hospitalization and mortality in patients with HF. Methods: Residents in an 11-county region in southeastern Minnesota with incident HF from 1/01/2013 to 3/31/2015 were identified using the International Classification of Diseases, Ninth Revision code 428 (n=3715) and prospectively surveyed to measure health literacy using established screening questions. A total of 1992 patients returned a survey (response rate 54%); 1779 patients with complete clinical data and adequate follow up were retained for analysis. Health literacy, measured as a composite on three 5-point scales, was categorized as adequate (≤ 10) or low (> 10). Cox proportional hazards regression and Andersen-Gill models were used to determine the association of health literacy with mortality and hospitalization. Results: Among 1779 patients (mean age 74, 53% male), 10% had low health literacy. After a mean follow-up of 8±4 months, 72 deaths and 600 hospitalizations occurred. Low health literacy was associated with increased mortality and hospitalizations (Figure). After adjusting for age, sex, comorbidity, education and marital status, the hazard ratio for death and hospitalization in patients with low health literacy was 2.84 (95% CI: 1.63, 4.96) and 1.43 (95% CI: 1.04, 1.96) respectively, compared to patients with adequate health literacy. Conclusions: Low health literacy is associated with increased risk of hospitalization and death among patients with HF. Health literacy is critical to the self-management demands of living with heart failure. Evaluation of health literacy in the clinical setting may guide inventions to target patients with low literacy.

scholarly journals Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

2021 ◽  
Author(s):  
Ma Cherrysse Ulsa ◽  
Xi Zheng ◽  
Peng Li ◽  
Arlen Gaba ◽  
Patricia M Wong ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Proportional Hazards ◽  
Time Lag ◽  
Cox Proportional Hazards ◽  
Poor Sleep ◽  
Cardiovascular Risks ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p&lt;0.001) and 57% (1.57 [1.38-1.80], p&lt;0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction &lt;0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

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