Estimating uncertainty when providing individual cardiovascular risk predictions: A Bayesian survival analysis.

BACKGROUND: Cardiovascular disease (CVD) risk scores provide point estimates of individual risk without uncertainty quantification. The objective of the current study was to demonstrate the feasibility and clinical utility of calculating uncertainty surrounding individual CVD-risk predictions using Bayesian methods. METHODS AND RESULTS: Individuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (UCC-SMART). In 8,355 individuals, followed for median of 8.2 years (IQR 4.2-12.5), a Bayesian Weibull model was derived to predict the 10-year risk of recurrent CVD events. Model coefficients and individual predictions were very similar to that of a traditional ('frequentist') model but the Bayesian model also predicted 95% credible intervals (CIs) surrounding individual risk estimates. The median width of the individual 95%CrI was 5.3% (IQR 3.6-6.5) and 17% of the population had a 95%CrI width of 10% or greater. The uncertainty decreased with increasing sample size used for derivation of the model. Combining the Bayesian Weibull model with sampled hazard ratios based on trial reports may be used to estimate individual absolute risk reduction with uncertainty measures and the probability that a treatment option will result in a clinically relevant risk reduction. INTERPRETATION: Estimating uncertainty surrounding individual CVD risk predictions using Bayesian methods is feasible. The uncertainty regarding individual risk predictions could have several applications in clinical practice, like the comparison of different treatment options or by calculating the probability of the individual risk being below a certain treatment threshold. However, as the individual uncertainty measures only reflect sampling error and no biases in risk prediction, physicians should be familiar with the interpretation before widespread clinical adaption.

Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population.

BACKGROUND: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied. OBJECTIVES: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004. METHODS: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease. RESULTS: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure. CONCLUSIONS: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.

High-Sensitivity Troponin T and I Among Pregnant Women in the US-The National Health and Nutrition Examination Survey, 1999-2004.

This cross-sectional study investigates the expected physiologic concentrations of high-sensitivity cardiac troponin in normal pregnancy.

Landscape characteristics influence ranging behavior of Asian elephants at the human-wildlands interface in Myanmar.

CONTEXT: Asian elephant numbers are declining across much of their range driven largely by serious threats from land use change resulting in habitat loss and fragmentation. Myanmar, holding critical range for the species, is undergoing major developments due to recent sociopolitical changes. To effectively manage and conserve the remaining populations of endangered elephants in the country, it is crucial to understand their ranging behavior. OBJECTIVES: Our objectives were to (1) estimate the sizes of dry, wet, and annual ranges of wild elephants in Myanmar; and quantify the relationship between dry season (the period when human-elephant interactions are the most likely to occur) range size and configurations of agriculture and natural vegetation within the range, and (2) evaluate how percentage of agriculture within dry core range (50% AKDE range) of elephants relates to their daily distance traveled. METHODS: We used autocorrelated kernel density estimator (AKDE) based on a continuous-time movement modeling (ctmm) framework to estimate dry season (26 ranges from 22 different individuals), wet season (12 ranges from 10 different individuals), and annual range sizes (8 individuals), and reported the 95%, 50% AKDE, and 95% Minimum Convex Polygon (MCP) range sizes. We assessed how landscape characteristics influenced range size based on a broad array of 48 landscape metrics characterizing aspects of vegetation, water, and human features and their juxtaposition in the study areas. To identify the most relevant landscape metrics and simplify our candidate set of informative metrics, we relied on exploratory factor analysis and Spearman's rank correlation coefficient. Based on this analysis we adopted a final set of metrics into our regression analysis. In a multiple regression framework, we developed candidate models to explain the variation in AKDE dry season range sizes based on the previously identified, salient metrics of landscape composition. RESULTS: Elephant dry season ranges were highly variable averaging 792.0 km2 and 184.2 km2 for the 95% and 50% AKDE home ranges, respectively. We found both the shape and spatial configuration of agriculture and natural vegetation patches within an individual elephant's range play a significant role in determining the size of its range. We also found that elephants are moving more (larger energy expenditure) in ranges with higher percentages of agricultural area. CONCLUSION: Our results provide baseline information on elephant spatial requirements and the factors affecting them in Myanmar. This information is important for advancing future land use planning that takes into account space-use requirements for elephants. Failing to do so may further endanger already declining elephant populations in Myanmar and across the species' range.

Glycemic excursions and subclinical cardiac damage in adults with type 2 diabetes: Results from the ADVANCE Trial.

We found that 1,5-anhydroglucitol-a marker of glucose excursions-was not independently associated with subclinical cardiac damage, nor with vascular outcomes, in the ADVANCE Trial. High-sensitivity cardiac troponin T and N-terminal pro-b-type natriuretic peptide provided better prognostic information regarding vascular risk in diabetes than 1,5-anhydroglucitol.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

An exploratory study of self-reported complicated grief symptoms in parentally bereaved adults with intellectual disability.

BACKGROUND: Complicated grief involves the experience of grief-related symptoms at a time, and severity, beyond which could be considered adaptive, while persistent complex bereavement disorder (PCBD) has been identified as a condition that requires further study in the typical population. The aims of this study are to (1) explore the symptoms of complicated grief associated with parental bereavement as self-reported by adults with intellectual disabilities (IDs) who have experienced a parental bereavement and (2) conduct an initial examination of how the existing criteria for PCBD apply to this group. METHODS: This study uses a comparative group design, assessing self and staff (proxy) reports for a group of parentally bereaved individuals and a matched group of non-bereaved individuals using the Complicated Grief Questionnaire - ID Self-Report. Participants were 46 individuals with ID, 30 (65%) of whom who had experienced a parental bereavement within the previous 2 years. The age range was 23-67 years (mean = 43.8; SD = 10.3). RESULTS: The results highlight the presence of a range of symptoms of complicated grief in individuals' self-reports, although there was some evidence that separation distress-related symptoms were more apparent. An analysis of individual symptoms showed patterns of higher reports among the bereaved group as would be expected. Comparing staff and self-reports, key criteria showed higher levels in self-reports among the bereaved group. CONCLUSIONS: This study has demonstrated the capacity of people with ID to self-report personal experience of symptoms of complicated grief, when appropriate and accessible assessment tools are used. Some symptoms were more evident among bereaved individuals (compared with non-bereaved participants), and they tended to be from separation distress criteria. This may indicate the relevance of these symptoms for people with ID and question the existing criteria for PCBD in this population, which may have clinical implications for supporting people with ID experiencing a more complicated bereavement response.

Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study.

AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.

Primary prevention aspirin among the elderly: challenges in translating trial evidence to the clinic.

The ASPirin in Reducing Events in the Elderly trial (ASPREE) contributed important knowledge about primary cardiovascular disease (CVD) prevention among healthy older adults. The finding that daily low-dose aspirin (LDA) does not statistically prevent disability or CVD among adults aged over 70 years when compared with placebo, but does significantly increase risk of haemorrhage, immediately influenced clinical practice guidelines. In this article, we discuss nuances of the trial that may impact the extrapolation of the ASPREE trial results to the everyday individual clinical care of older adults.

Relation of Dietary Sodium Intake With Subclinical Markers of Cardiovascular Disease (from MESA).

The associations between dietary sodium intake and markers of subclinical cardiovascular disease (CVD), such as high-sensitivity cardiac troponin T (hs-cTnT) and amino terminal pro b-type natriuretic peptide (NT-proBNP), may provide mechanistic insight into the relation between dietary sodium and cardiovascular events. We studied 6,131 participants of the Multi-Ethnic Study of Atherosclerosis, who were free of clinical CVD at baseline. Food frequency questionnaires were used to assess estimated sodium intake (ESI) at baseline. We tested the associations between 5 quintiles of ESI (quintile 1: 0.2 to 1.3 grams/day, quintile 2: 1.3 to 1.8 grams/day, quintile 3: 1.8 to 2.4 grams/day, quintile 4: 2.4 to 3.2 grams/day, and quintile 5: 3.2 to 9.9 grams/day) with cross-sectional and 5-year longitudinal change in hs-cTnT and NT-proBNP concentrations. Restricted cubic spline plots were utilized to explore the shape of the associations between ESI and biomarker outcomes. A cross-sectional association between baseline sodium intake and hs-cTnT (but not NT-proBNP) was observed, driven predominantly by a strong positive relation at an intake range of 0.2 to 2.4 g/day. Conversely, a longitudinal association between baseline sodium intake and NT-proBNP (but not hs-cTnT) was observed, driven predominantly by a strong positive relation at intake levels ≥2.4 g/day. In conclusion, temporal shifts in the association between increased ESI and markers of subclinical CVD, hs-cTnT in the short term and NT-proBNP in the longer term, point to the complex pathobiology of the association between sodium intake and CVD. There was also no consistent evidence supporting a J-curve (i.e., excess biomarker values at very low ESI).

Maternal effects obscure condition-dependent sex allocation in changing environments.

Climate change increases environmental fluctuations which thereby impact population demography. Species with temperature-dependent sex determination may experience more extreme sex ratio skews, but this has not been considered in species with chromosomally determined sex. However, anticipatory maternal effects cause lifelong physiological changes impacting sex ratios. Here we show, in mice, that more sons were born to mothers in good condition when their breeding environment matched their gestational environment, consistent with theoretical predictions, but mothers in mismatched environments have no condition-sex ratio relationship. Thus, the predicted effect of condition on sex ratio was obscured by maternal effects when the environment changed. This may explain extreme sex ratio skews in reintroduced or translocated populations, and sex ratio skews may become more common and less predictable with accelerating environmental change.

Heavy rainfall triggers increased nocturnal flight in desert populations of the Pacific black duck (Anas superciliosa).

Understanding of avian nocturnal flight comes mainly from northern hemisphere species in seasonal temperate ecosystems where nocturnal flight is often precisely timed and entrained by annual photoperiod. Here we investigate patterns of nocturnal flight in waterbirds of Australian desert ecosystems that fly considerable distances to find temporary water bodies formed from rainfall which is highly unpredictable seasonally and spatially, and when there is sufficient water, they then breed. How they perform these feats of navigation and physiology remain poorly known. Using GPS tracking of 38 satellite tagged Pacific black ducks (Anas superciliosa) in two contrasting ecosystems, before and after heavy rainfall we revealed a key role for facultative nocturnal flight in the movement ecology of this species. After large rainfall events, birds rapidly increased nocturnal flight activity in the arid aseasonal ecosystem, but not in the mesic seasonal one. Nocturnal flights occurred throughout the night in both ecosystems. Long range flights (>50 km in 2 hours) occurred almost exclusively at night; at night the distance flown was higher than during the day, birds visited more locations, and the locations were more widely dispersed. Our work reveals that heavy rainfall triggers increased nocturnal flight activity in desert populations of waterbirds.

Do men and women with intellectual disabilities understand death?

BACKGROUND: Individuals with ID are often withheld information about the death of their loved ones as it has often been thought that they do not understand death or cannot grieve. This grief exacerbates the stress of individuals with ID as they often encounter secondary losses such as transitioning to a care facility. The aim of this study is to investigate men and women with ID understanding death concepts and to what extent. METHOD: Adopting a stratified random sampling method, 156 Chinese people with ID were invited to join the study. One hundred and ten participants were interviewed using simple death related vignettes expanding upon and replicating a published study carried out in Ireland. The understanding of the five death concepts: causality, irreversibility, nonfunctionality, universality and inevitability was examined. The correlates of demographics, bereavement experiences and comprehension were explored. RESULTS: The majority of the participants did understand concepts such as death is irreversible and that the deceased no longer function. One third of the participants understood causality and the universality of death. One fifth understood the inevitability of death. Previous bereavement experiences were correlated with higher understanding. Communication and community skills were correlated with all concepts of death except universality. CONCLUSION: The results indicate that individuals with ID do have a partial to full understanding of the concepts of death. The culture of Hong Kong is one that considers death to be a taboo or unlucky subject. Therefore, the results mirror the the lack of understanding of universality and inevitability concepts as it is forbidden to speak of these concepts. An open and honest environment is encouraged to educate individuals with ID about death and bereavement.