Severe Painful Vaso-Occlusive Crises and Mortality in a Contemporary Adult Sickle Cell Anemia Cohort Study

Background

Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

Methods

Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.

Results

Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.

Conclusions

Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.

Trial Registration

ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/     

A Prospective Cohort Study Examining the Associations of Dietary Calcium Intake with All-Cause and Cardiovascular Mortality in Older Chinese Community-Dwelling People

Background

Most epidemiological studies of calcium intake and mortality risk have been conducted in populations with moderate to high calcium intake, and limited studies have focused on populations with low habitual calcium intake (i.e., mean dietary calcium intake <700 mg/d).

Objective

This study investigated the association between dietary calcium intake and death from all causes and cardiovascular disease in Chinese population with low habitual calcium intake.

Design

Data from 3,139 Chinese men and women in a population-based prospective cohort study, aged >=65 years and free of heart diseases or stroke at baseline, were analyzed. Primary outcome measures, identified from the death registry, were death from all causes and cardiovascular disease. Dietary calcium intake assessed using a validated food frequency questionnaire was categorized into sex-specific quartiles. Data on use of supplemental calcium (yes or no) including individual calcium supplements and other calcium containing supplement were collected. Cox regression models adjusted for demographic and lifestyle variables were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI).

Results

During a median of 9.1 years of follow-up, 529 all-cause deaths (344 men, 185 women) and 114 (74 men, 40 women) deaths from cardiovascular disease were identified. An inverse trend between dietary calcium intake and mortality was observed. Compared with the lowest quartile (<458 mg/d for men, <417 mg/d for women), the highest quartile of dietary calcium intake (>762 mg/d for men, >688 mg/d for women) had a significantly reduced risk of all-cause mortality (multivariate HR=0.63, 95% CI=0.49-0.81, P _trend<0.001) but an insignificant decreased risk of cardiovascular mortality (multivariate HR=0.70, 95% CI=0.41-1.21, P _trend=0.228). Similar inverse association was observed when the analyses were stratified on calcium supplemental use.

Conclusions

Higher intake of dietary calcium was associated with reduced risk of all-cause mortality and possibly cardiovascular mortality in Chinese older people with low habitual calcium intake.     

Lifestyle Factors,Medication Use and Risk for Ischaemic Heart Disease Hospitalisation: A Longitudinal Population-Based Study

Background

Lifestyle factors have been implicated in ischaemic heart disease (IHD) development however a limited number of longitudinal studies report results stratified by cardio-protective medication use.

Purpose

This study investigated the influence of self-reported lifestyle factors on hospitalisation for IHD, stratified by blood pressure and/or lipid-lowering therapy.

Methods

A population-based cohort of 14,890 participants aged 45+ years and IHD-free was identified from the Western Australian Health and wellbeing Surveillance System (2004 to 2010 inclusive), and linked with hospital administrative data. Adjusted hazard ratios for future IHD-hospitalisation were estimated using Cox regression.

Results

Current smokers remained at higher risk for IHD-hospitalisation (adjusted HR=1.57; 95% CI: 1.22-2.03) after adjustment for medication use, as did those considered overweight (BMI=25-29 kg/m²; adjusted HR=1.28; 95% CI: 1.04-1.57) or obese (BMI of ≥30kg/m²; adjusted HR=1.31; 95% CI: 1.03-1.66). Weekly leisure-time physical activity (LTPA) of 150 minutes or more and daily intake of 3 or more fruit/vegetable servings reduced risk by 21% (95% CI: 0.64-0.97) and 26% (95% CI: 0.58-0.96) respectively. Benefits of LTPA appeared greatest in those on blood pressure lowering medication (adjusted HR=0.50; 95% CI: 0.31-0.82 [for LTPA<150 mins], adjusted HR=0.64; 95% CI: 0.42-0.96 [for LTPA>=150 mins]). IHD risk in smokers was most pronounced in those taking neither medication (adjusted HR=2.00; 95% CI: 1.41-2.83).

Conclusion

This study confirms the contribution of previously reported lifestyle factors towards IHD hospitalisation, even after adjustment for antihypertensive and lipid-lowering medication use. Medication stratified results suggest that IHD risks related to LTPA and smoking may differ according to medication use.     

Reductions in Cardiovascular,Cerebrovascular, and Respiratory Mortality following the National Irish Smoking Ban: Interrupted Time-Series Analysis

Background

Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality.

Methods

A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence.

Results

Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76–0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63–0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54–0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46–0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35–64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32–0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305–4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking.

Conclusions

The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in cerebrovascular and respiratory causes.     

Body Mass Index and Mortality in Non-Hispanic Black Adults in the NIH-AARP Diet and Health Study

Background

Although the prevalence of obesity (body mass index, kg/m², BMI ≥30) is higher in non-Hispanic blacks than in non-Hispanic whites, the relation of BMI to total mortality in non-Hispanic blacks is not well defined.

Purpose

We investigated the association between BMI and total mortality in 16,471 non-Hispanic blacks in the NIH-AARP Diet and Health Study, a prospective cohort of adults aged 50–71 years.

Methods

During an average of 13 years of follow-up, 2,609 deaths were identified using the Social Security Administration Death Master File and the National Death Index. Cox proportional hazard models were used to estimate relative risks and two-sided 95% confidence intervals (CI), adjusting for potential confounders.

Results

Among individuals with no history of cancer or heart disease at baseline and had a BMI of 20 or greater, the relative risk for total death was 1.12 (95% CI:1.05, 1.19, for a 5-unit increase in BMI) in men and 1.09 (95% CI:1.03, 1.15) in women. Among never smokers with no history of cancer or heart disease at baseline, relative risks for total death for BMI 25–<30, 30–<35, 35–<40, and 40–50, compared with BMI 20–<25, were 1.27 (95% CI: 0.91, 1.78), 1.56 (95% CI: 1.07, 2.28), 2.48 (95% CI: 1.53, 4.05), and 2.80 (95% CI: 1.46, 5.39), respectively, in men and 0.78 (95% CI: 0.59, 1.04), 1.17 (95% CI: 0.88, 1.57), 1.35 (95% CI: 0.96, 1.90), and 1.93 (95% CI: 1.33, 2.81), respectively, in women.

Conclusions

Our findings suggest that overweight is related to an increased risk of death in black men, but not in black women, while obesity is related to an increased risk of death in both black men and women. A large pooled analysis of existing studies is needed to systematically evaluate the association between a wide range of BMIs and total mortality in blacks.     

Changes of Body Mass Index in Relation to Mortality: Results of a Cohort of 42,099 Adults

Background

High Body-Mass-Index (BMI) is associated with increased all-cause mortality, but little is known about the effect of short- and long-term BMI change on mortality. The aim of the study was to determine how long-term weight change affects mortality.

Methods and findings

Within a population-based prospective cohort of 42,099 Austrian men and women (mean age 43 years) with at least three BMI measurements we investigated the relationship of BMI at baseline and two subsequent BMI change intervals of five years each with all-cause mortality using Cox proportional Hazard models. During median follow-up of 12 years 4,119 deaths were identified. The lowest mortalities were found in persons with normal weight or overweight at baseline and stable BMI over 10 years. Weight gain (≥0.10 kg/m²/year) during the first five years was associated with increased mortality in overweight and obese people. For weight gain during both time intervals mortality risk remained significantly increased only in overweight (Hazard Ratio (HR): 1.39 (95% confidence interval: 1.01; 1.92)) and obese women (1.85 (95% confidence interval: 1.18; 2.89)). Weight loss (< −0.10 kg/m²/year) increased all-cause mortality in men and women consistently. BMI change over time assessed using accepted World Health Organisation BMI categories showed no increased mortality risk for people who remained in the normal or overweight category for all three measurements. In contrast, HRs for stable obese men and women were 1.57 (95% CI: 1.31; 1.87) and 1.46 (95% CI: 1.25; 1.71) respectively.

Conclusion

Our findings highlight the importance of weight stability and obesity avoidance in prevention strategy.     

Mortality after Hospitalization for Pneumonia among Individuals with HIV, 1995–2008: A Danish Cohort Study

Background

HIV–infected persons are at increased risk of pneumonia, even with highly active antiretroviral treatment (HAART). We examined the impact of pneumonia on mortality and identified prognostic factors for death among HIV–infected.

Methodology/Principal Findings

In a nationwide, population-based cohort of individuals with HIV, we included persons hospitalized with pneumonia from the Danish National Hospital Registry and obtained mortality data from the Danish Civil Registration System. Comparing individuals with and without pneumonia, we used Poisson regression to estimate relative mortality and logistic regression to examine prognostic factors for death following pneumonia. From January 1, 1995, to July 1, 2008, we observed 699 episodes of first hospitalization for pneumonia among 4,352 HIV patients. Ninety-day mortality after pneumonia decreased from 22.4% (95% confidence interval [CI]: 16.5%–28.9%) in 1995–1996 to 8.4% (95% CI: 6.1%–11.6%) in 2000–2008. Mortality remained elevated for more than a year after hospitalization for pneumonia: adjusted mortality rate ratio 5.38 (95% CI: 4.27–6.78), 1.80 (95% CI: 1.36–2.37), and 1.62 (95% CI: 1.32–2.00) for days 0–90, 91–365, and 366+, respectively. The following variables predicted mortality within 90 days following hospitalization for pneumonia (adjusted Odds Ratios): male sex (3.77, 95% CI: 1.37–10.4), Charlson Comorbidity Index score ≥2 (3.86, 95% CI: 2.19–6.78); no current HAART (3.58, 95% CI: 1.83–6.99); history of AIDS (2.46, 95% CI: 1.40–4.32); age per 10 year increase (1.43, 95% CI: 1.11–1.85); and CD4+ cell count ≤200 (2.52, 95% CI: 1.37–4.65).

Conclusions/Significance

The first hospitalization for pneumonia among HIV–infected individuals was associated with elevated risk of death up to more than a year later. Use of HAART decreased the risk, independent of current CD4+ cell count. Prognosis following pneumonia improved over calendar time.     

Health Factors and Risk of All-Cause,Cardiovascular, and Coronary Heart Disease Mortality: Findings from the MONICA and HAPIEE Studies in Lithuania

Aims

This study investigated the trends and levels of the prevalence of health factors, and the association of all-cause and cardiovascular (CVD) mortality with healthy levels of combined risk factors among Lithuanian urban population.

Methods

Data from five general population surveys in Kaunas, Lithuania, conducted between 1983 and 2008 were used. Healthy factors measured at baseline include non-smoking, normal weight, normal arterial blood pressure, normal level of total serum cholesterol, normal physical activity and normal level of fasting glucose. Among 9,209 men and women aged 45–64 (7,648 were free from coronary heart disease (CHD) and stroke at baseline), 1,219 death cases from any cause, 589 deaths from CVD, and 342 deaths from CHD occurred during follow up. Cox proportional hazards regression was used to estimate the association between health factors and mortality from all causes, CVD and CHD.

Results

Between 1983 and 2008, the proportion of subjects with 6 healthy levels of risk factors was higher in 2006–2008 than in 1983–1984 (0.6% vs. 0.2%; p = 0.09), although there was a significant increase in fasting glucose and a decline in intermediate physical activity. Men and women with normal or intermediate levels of risk factors had significantly lower all-cause, CVD and CHD mortality risk than persons with high levels of risk factors. Subjects with 5–6 healthy factors had hazard ratio (HR) of CVD mortality 0.35 (95% confidence interval (CI) 0.15–0.83) compared to average risk in the whole population. The hazard ratio for CVD mortality risk was significant in men (HR 0.34, 95% CI 0.12–0.97) but not in women (HR 0.38, 95% CI 0.09–1.67).

Conclusions

An inverse association of most healthy levels of cardiovascular risk factors with risk of all-cause and CVD mortality was observed in this urban population-based cohort. A greater number of cardiovascular health factors were related with significantly lower risk of CVD mortality, particularly among men.     

Estimated Glomerular Filtration Rate,All-Cause Mortality and Cardiovascular Diseases Incidence in a Low Risk Population: The MATISS Study

Background

Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far.

Design

Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD.

Methods

Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula.

Results

At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m² and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73m², respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors.

Conclusions

These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.     

Red Cell Distribution Width and Other Red Blood Cell Parameters in Patients with Cancer: Association with Risk of Venous Thromboembolism and Mortality

Background

Cancer patients are at high risk of developing venous thromboembolism (VTE). Red cell distribution width (RDW) has been reported to be associated with arterial and venous thrombosis and mortality in several diseases. Here, we analyzed the association between RDW and other red blood cell (RBC) parameters with risk of VTE and mortality in patients with cancer.

Methods

RBC parameters were measured in 1840 patients with cancers of the brain, breast, lung, stomach, colon, pancreas, prostate, kidney; lymphoma, multiple myeloma and other tumor sites, that were included in the Vienna Cancer and Thrombosis Study (CATS), which is an ongoing prospective, observational cohort study of patients with newly diagnosed or progressive cancer after remission. Primary study outcome is occurrence of symptomatic VTE and secondary outcome is death during a maximum follow-up of 2 years.

Results

During a median follow-up of 706 days, 131 (7.1%) patients developed VTE and 702 (38.2%) died. High RDW (>16%) was not associated with a higher risk of VTE in the total study cohort; in competing risk analysis accounting for death as competing variable the univariable subhazard ratio (SHR) was 1.34 (95% confidence interval [CI]: 0.80–2.23, p = 0.269). There was also no significant association between other RBC parameters and risk of VTE. High RDW was associated with an increased risk of mortality in the total study population (hazard ratio [HR, 95% CI]: 1.72 [1.39–2.12], p<0.001), and this association prevailed after adjustment for age, sex, hemoglobin, leukocyte and platelet count (HR [95% CI]: 1.34 [1.06–1.70], p = 0.016).

Conclusions

RDW and other RBC parameters were not independently associated with risk of VTE in patients with cancer and might therefore not be of added value for estimating risk of VTE in patients with cancer. We could confirm that high RDW is an independent predictor of poor overall survival in cancer.     

Effects of Zinc Supplementation on the Incidence of Mortality in Preschool Children: A Meta-Analysis of Randomized Controlled Trials

Background

Previous trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality.

Methodology and Principal Findings

We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56–1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53–1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11–2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77–1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67–1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.

Conclusions/Significance

Zinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.     

Influence of Maternal Height and Weight on Low Birth Weight: A Cross-Sectional Study in Poor Communities of Northeastern Brazil

Background

Low birth weight (LBW) is associated with an increased risk of mortality, adverse metabolic conditions, and long-term chronic morbidities. The relationship between LWB and short maternal stature coupled with nutritional status was investigated in poor communities.

Methods/Principal Findings

A cross-sectional population-based study involving 2226 mother-child pairs was conducted during the period 2009-2010 in shantytowns of Maceió, Alagoas, Brazil. Associations between LBW and maternal sociodemographics, stature and nutritional status were investigated. The outcome variable was birth weight (< 2500g and ≥ 2500g). The independent variables were the age, income, educational background, stature and nutritional status (eutrophic, underweight, overweight and obese) of the mother. The frequency of LBW was 10%. Short-statured mothers (1^st quartile of stature ≤ 152cm) showed a tendency of increased risk of LBW children compared to mothers in the 4^th quartile of stature (>160.4cm) (OR: 1.42, 95% CI: 0.96 - 1.09, p = 0.078). Children from short-statured mothers weighed an average of 125g less than those from taller mothers (3.18±0.56kg vs. 3.30±0.58kg, respectively p = 0.002). Multivariate analyses showed that short stature, age < 20y (OR: 3.05, 95% CI:1.44 - 6.47) or were underweight (OR: 2.26, 95% CI:0.92 - 5.95) increased the risk of LBW, while overweight (OR: 0.38, 95% CI:0.16 - 0.95) and obesity (OR: 0.39, 95% CI:0.11 - 1.31) had lower risk for LBW. In taller mothers, lower income and underweight were associated with LBW (OR: 1.88, 95% CI: 1.07 - 3.29 and 2.85, 95% CI:1.09 - 7.47, respectively), and obese mothers showed a trend of increased risk of LBW (OR: 1.66, 95% CI:0.84 - 3.25).

Conclusions/Significance

Overweight was found to have a protective effect in short-statured mothers, indicating that a surplus of energy may diminish the risk of LBW. Short-statured younger mothers, but not taller ones, showed higher risk of LBW. The mother being underweight, regardless of stature, was associated with LBW.     

The Relationship of Walking Intensity to Total and Cause-Specific Mortality. Results from the National Walkers’ Health Study

Purpose

Test whether: 1) walking intensity predicts mortality when adjusted for walking energy expenditure, and 2) slow walking pace (≥24-minute mile) identifies subjects at substantially elevated risk for mortality.

Methods

Hazard ratios from Cox proportional survival analyses of all-cause and cause-specific mortality vs. usual walking pace (min/mile) in 7,374 male and 31,607 female recreational walkers. Survival times were left censored for age at entry into the study. Other causes of death were treated as a competing risk for the analyses of cause-specific mortality. All analyses were adjusted for sex, education, baseline smoking, prior heart attack, aspirin use, diet, BMI, and walking energy expenditure. Deaths within one year of baseline were excluded.

Results

The National Death Index identified 1968 deaths during the average 9.4-year mortality surveillance. Each additional minute per mile in walking pace was associated with an increased risk of mortality due to all causes (1.8% increase, P=10^-5), cardiovascular diseases (2.4% increase, P=0.001, 637 deaths), ischemic heart disease (2.8% increase, P=0.003, 336 deaths), heart failure (6.5% increase, P=0.001, 36 deaths), hypertensive heart disease (6.2% increase, P=0.01, 31 deaths), diabetes (6.3% increase, P=0.004, 32 deaths), and dementia (6.6% increase, P=0.0004, 44 deaths). Those reporting a pace slower than a 24-minute mile were at increased risk for mortality due to all-causes (44.3% increased risk, P=0.0001), cardiovascular diseases (43.9% increased risk, P=0.03), and dementia (5.0-fold increased risk, P=0.0002) even though they satisfied the current exercise recommendations by walking ≥7.5 metabolic equivalent (MET)-hours per week.

Conclusions

The risk for mortality: 1) decreases in association with walking intensity, and 2) increases substantially in association for walking pace ≥24 minute mile (equivalent to <400m during a six-minute walk test) even among subjects who exercise regularly.     

Prognosis and Risk Factors for Deterioration in Patients Admitted to a Medical Emergency Department

Objective

Patients that initially appear stable on arrival to the hospital often have less intensive monitoring of their vital signs, possibly leading to excess mortality. The aim was to describe risk factors for deterioration in vital signs and the related prognosis among patients with normal vital signs at arrival to a medical emergency department (MED).

Design and setting

Single-centre, retrospective cohort study of all patients admitted to the MED from September 2010-August 2011.

Subjects

Patients were included when their vital signs (systolic blood pressure, pulse rate, respiratory rate, Glasgow Coma Scale, oxygen saturation and temperature) were within the normal range at arrival. Deterioration was defined as a deviation from the defined normal range 2–24 hours after arrival.

Results

4292 of the 6257 (68.6%) admitted to the MED had a full set of vital signs at first presentation, 1440/4292 (33.6%) had all normal vital signs and were included in study, 44.0% were male, median age 64 years (5th/95th percentile: 21–90 years) and 446/1440 (31.0%) deteriorated within 24 hours. Independent risk factors for deterioration included age 65–84 years odds ratio (OR): 1.79 (95% confidence interval [CI]: 1.27–2.52), 85+ years OR 1.67 (95% CI: 1.10–2.55), Do-not-attempt-to-resuscitate order OR 3.76 (95% CI: 1.37–10.31) and admission from the open general ED OR 1.35 (95% CI: 1.07–1.71). Thirty-day mortality was 7.9% (95% CI: 5.5–10.7%) among deteriorating patients and 1.9% (95% CI: 1.2–3.0%) among the non-deteriorating, hazard ratio 4.11 (95% CI: 2.38–7.10).

Conclusions

Among acutely admitted medical patients who arrive with normal vital signs, 31.0% showed signs of deterioration within 24 hours. Risk factors included old age, Do-not-attempt-to-resuscitate order, admission from the open general ED. Thirty-day mortality among patients with deterioration was four times higher than among non-deteriorating patients. Further research is needed to determine whether intensified monitoring of vital signs can help to prevent deterioration or mortality among medical emergency patients.     

Population Seroprevalence Study after a West Nile Virus Lineage 2 Epidemic,Greece, 2010

Introduction

During summer 2010, 262 human cases including 35 deaths from West Nile virus (WNV) infection were reported from Central Macedonia, Greece. Evidence from mosquitoes, birds and blood donors demonstrated that the epidemic was caused by WNV lineage 2, which until recently was considered of low virulence. We conducted a household seroprevalence study to estimate the spread of infection in the population during the epidemic, ascertain the relationship of infection to clinical disease, and identify risk factors for infection.

Methods

We used a two-stage cluster design to select a random sample of residents aged ≥18 years in the outbreak epicentre. We collected demographic, medical, and risk factor data using standard questionnaires and environmental checklists, and tested serum samples for presence of WNV IgG and IgM antibodies using ELISA.

Results

Overall, 723 individuals participated in the study, and 644 blood samples were available. Weighted seropositivity for IgG antibodies was 5.8% (95% CI: 3.8–8.6; n=41). We estimated that about 1 in 130 (1:141 to 1:124) infected individuals developed WNV neuroinvasive disease, and approximately 18% had clinical manifestations attributable to their infection. Risk factors for infection reflected high exposure to mosquitoes; rural residents were particularly at risk (prevalence ratio: 8.2, 95% CI: 1.1–58.7).

Discussion

This study adds to the evidence that WNV lineage 2 strains can cause significant illness, demonstrating ratios of infection to clinical disease similar to those found previously for WNV lineage 1.     

Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

Background

Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied.

Methods and Findings

A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na⁺ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome rate.

Conclusions

The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes.     

Prevalence and Clinical Characteristics Associated with Pulmonary Hypertension in African-Americans

Background

Pulmonary hypertension (PH) is associated with increased mortality and morbidity. It is frequently associated with cardiopulmonary diseases that are prevalent in African Americans (AAs). However, the prevalence or determinants of PH in the AA population is not known.

Methods

We conducted a cross-sectional study to estimate the prevalence of PH (defined as trans-tricuspid gradient ≥ 35 mm Hg) and associated clinical characteristics in AAs using the Jackson Heart Study cohort (n=3,282) who underwent echocardiography and had a measurable trans-tricuspid regurgitant jet. Echocardiography is frequently used for screening for PH despite its limitations in estimating accurate PA systolic pressures. Overall and age-adjusted gender-specific prevalence were estimated and modified Poisson regression was used to identify independent clinical, spirometric, and echocardiographic characteristics associated with PH.

Results

The mean age of the study population was 56.1 ± 12.6 years with 67.5% female. The prevalence of PH was 6.8%, with higher prevalence in female AAs (age-adjusted prevalence: Men 4.9%, 95% CI 3.6-6.2%; Women 7.7%, 95% CI 6.6-8.8%). Pulmonary hypertension prevalence increased with age (Prevalence Ratio: 10.0, 95%CI 4.0-25.1, >65 versus <45 years old), presence of obesity, higher pulse pressure, diabetes, obstructive or restrictive spirometry pattern, and severe left heart valvular disease. Also, PH was significantly associated with left atrial size and left ventricular ejection fraction.

Conclusions

Pulmonary hypertension is prevalent in AAs, more in women than in men. The identified cardiopulmonary risk factors that increase the prevalence of PH may assist in diagnosis and management of these at-risk subjects in the AA population.     

Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study

Background

Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.

Methods

In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined.

Findings

Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005).After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia.The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009.

Interpretation

A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.     

Use of Thiopurines and Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Diseases: A Meta-Analysis

Objective

Inflammatory bowel disease (IBD) is commonly treated with thiopurines such as azathioprine and mercaptopurine for the maintenance of remission. Studies examining chemopreventive of these medications on colorectal neoplasm in IBD patients have yielded conflicting results. We performed a meta-analysis to assess the role of thiopurines for this indication.

Methods

We performed a systematic search of PubMed, Web of Science, EMBASE and Cochrane to identify studies reporting colorectal neoplasm from IBD patients treated with thiopurines and conducted a meta-analysis of pooled relative risk (RR) using the random effects model.

Results

Nine case-control and ten cohort studies fulfilled the inclusion criteria. The use of thiopurines was associated with a statistically significant decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54–0.94, p=0.017), even after adjustment for duration and extent of the disease, but there was high heterogeneity among studies (I ²=68.0%, p<0.001). The RR of advanced neoplasm (high-grade dysplasia and cancer) was 0.72 (95%CI=0.50–1.03, p=0.070) and that of cancer was 0.70 (95% CI=0.46–1.09, p=0.111) for thiopurine-treated patients. Heterogeneity of the studies was affected by the sample size (</≥100 cases) and whether the patients had longstanding colitis (≥7 years).

Conclusion

The current meta-analysis revealed that thiopurines had a chemopreventive effect of colorectal neoplasms and a tendency of reducing advanced colorectal neoplasms in IBD. Due to the heterogeneity of included studies, these results should be interpreted with caution.