Impact of Hiv-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

Objectives

To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS).

Design, Setting

Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.

Subjects, Participants

36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27).

Outcome Measures

Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation.

Results

There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21–5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97–2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74–4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80–3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80–3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi’s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates.

Conclusions

A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research.     

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

Background

Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models.

Methods

Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models.

Results

The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment.

Conclusion

Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.     

Mortality and Life Expectancy in Homeless Men and Women in Rotterdam: 2001–2010

Background

Data on mortality among homeless people are limited. Therefore, this study aimed to describe mortality patterns within a cohort of homeless adults in Rotterdam (the Netherlands) and to assess excess mortality as compared to the general population in that city.

Methods

Based on 10-year follow-up of homeless adults aged ≥ 20 years who visited services for homeless people in Rotterdam in 2001, and on vital statistics, we assessed the association of mortality with age, sex and type of service used (e.g. only day care, convalescence care, other) within the homeless cohort, and also compared mortality between the homeless and general population using Poisson regression. Life tables and decomposition methods were used to examine differences in life expectancy.

Results

During follow-up, of the 2096 adult homeless 265 died. Among the homeless, at age 30 years no significant sex differences were found in overall mortality rates and life expectancy. Compared with the general Rotterdam population, mortality rates were 3.5 times higher in the homeless cohort. Excess mortality was larger in women (rate ratio [RR] RR 5.56, 95% CI 3.95–7.82) as compared to men (RR 3.31, 95% CI 2.91–3.77), and decreased with age (RR 7.67, 95% CI 6.87–8.56 for the age group 20–44 and RR 1.63, 95% CI 1.41–1.88 for the age group 60+ years). Life expectancy at age 30 years was 11.0 (95% CI 9.1–12.9) and 15.9 (95% CI 10.3–21.5) years lower for homeless men and women compared to men and women in the general population respectively.

Conclusion

Homeless adults face excessive losses in life expectancy, with greatest disadvantages among homeless women and the younger age groups.     

Association of Primary Care Characteristics with Variations in Mortality Rates in England: An Observational Study

Background

Wide variations in mortality rates persist between different areas in England, despite an overall steady decline. To evaluate a conceptual model that might explain how population and service characteristics influence population mortality variations, an overall null hypothesis was tested: variations in primary healthcare service do not predict variations in mortality at population level, after adjusting for population characteristics.

Methodology/Principal Findings

In an observational study of all 152 English primary care trusts (geographical groupings of population and primary care services, total population 52 million), routinely available published data from 2008 and 2009 were modelled using negative binomial regression. Counts for all-cause, coronary heart disease, all cancers, stroke, and chronic obstructive pulmonary disease mortality were analyzed using explanatory variables of relevant population and service-related characteristics, including an age-correction factor. The main predictors of mortality variations were population characteristics, especially age and socio-economic deprivation. For the service characteristics, a 1% increase in the percentage of patients on a primary care hypertension register was associated with decreases in coronary heart disease mortality of 3% (95% CI 1–4%, p = 0.006) and in stroke mortality of 6% (CI 3–9%, p<0.0001); a 1% increase in the percentage of patients recalling being better able to see their preferred doctor was associated with decreases in chronic obstructive pulmonary disease mortality of 0.7% (CI 0.2–2.0%, p = 0.02) and in all cancer mortality of 0.3% (CI 0.1–0.5%, p = 0.009) (continuity of care). The study found no evidence of an association at primary care trust population level between variations in achievement of pay for performance and mortality.

Conclusions/Significance

Some primary healthcare service characteristics were also associated with variations in mortality at population level, supporting the conceptual model. Health care system reforms should strengthen these characteristics by delivering cost-effective evidence-based interventions to whole populations, and fostering sustained patient-provider partnerships.     

Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada

Background

Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000–2007 in the U.S. and Canada.

Methods

Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants'' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.

Results

The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000–2002 to 2006–2007. Men and women had comparable life expectancies in all periods except the last (2006–2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm³.

Conclusions

A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.     

Sex Specific Incidence Rates of Type 2 Diabetes and Its Risk Factors over 9 Years of Follow-Up: Tehran Lipid and Glucose Study

Objective

To investigate the population-based incidence of type 2 diabetes and its potential risk factors in a sex-split cohort of Iranian population.

Materials and Methods

A total of 8400 non-diabetic participants, aged ≥20 years (3620 men and 4780 women) entered the study. Crude and age standardized incidence rates per 1000 person-years were calculated for whole population and each sex separately. Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals for all potential risk factors in both uni-variable and multivariable models.

Results

During a median follow-up of 9.5 years, 736 new cases of diabetes were identified, including 433 women and 303 men. The annual crude and age-standardized incidence rates (95% CI) of diabetes in the total population were 10.6 (9.92–11.4) and 9.94 (7.39–13.6) per 1000 person-years of follow-up and the corresponding sex specific rates were 10.2 (9.13–11.4) and 9.36 (5.84–14.92) in men and 11.0 (9.99–12.0) and 10.1 (7.24–13.9) in women, respectively. In the multivariable model, the risk for incident diabetes was significantly associated with fasting and 2 hour post challenge plasma glucose as well as family history of diabetes in both men and women. However, among women, only the contribution of wrist circumference to incident diabetes achieved statistical significance [HR: 1.16 (1.03–1.31)] with waist/height ratio being marginally significant [HR: 1.02 (0.99–1.04)]; while among men, only body mass index was a significant predictor [HR: 1.12 (1.02–1.22)]. Additionally, low education level conferred a higher risk for incident diabetes only among men [HR: 1.80 (1.23–2.36); P for interaction with sex = 0.003].

Conclusion

Overall, sex did not significantly modify the impact of risk factors associated with diabetes among Iranian adults; however, among modifiable risk factors, the independent role of lower education and general adiposity in men and central adiposity in women might require different preventive strategies.     

Treatment Initiation,Program Attrition and Patient Treatment Outcomes Associated with Scale-Up and Decentralization of HIV Care in Rural Malawi

Objective

To describe patient antiretroviral therapy (cART) outcomes associated with intensive decentralization of services in a rural HIV program in Malawi.

Methods

Longitudinal analysis of data from HIV-infected patients starting cART between August 2001 and December 2008 and of a cross-sectional immunovirological assessment conducted 12 (±2) months after therapy start. One-year mortality, lost to follow-up, and attrition (deaths and lost to follow-up) rates were estimated with exact Poisson 95% confidence intervals (CI) by type of care delivery and year of initiation. Association of virological suppression (<50 copies/mL) and immunological success (CD4 gain ≥100 cells/µL), with type of care was investigated using multiple logistic regression.

Results

During the study period, 4322 cART patients received centralized care and 11,090 decentralized care. At therapy start, patients treated in decentralized health facilities had higher median CD4 count levels (167 vs. 130 cell/µL, P<0.0001) than other patients. Two years after cART start, program attrition was lower in decentralized than centralized facilities (9.9 per 100 person-years, 95% CI: 9.5–10.4 vs. 20.8 per 100 person-years, 95% CI: 19.7–22.0). One year after treatment start, differences in immunological success (adjusted OR = 1.23, 95% CI: 0.83–1.83), and viral suppression (adjusted OR = 0.80, 95% CI: 0.56–1.14) between patients followed at centralized and decentralized facilities were not statistically significant.

Conclusions

In rural Malawi, 1- and 2-year program attrition was lower in decentralized than in centralized health facilities and no statistically significant differences in one-year immunovirological outcomes were observed between the two health care levels. Longer follow-up is needed to confirm these results.     

Excess mortality rate during adulthood among Danish adoptees

Background and objective

Adoption studies have been used to disentangle the influence of genes from shared familial environment on various traits and disease risks. However, both the factors leading to adoption and living as an adoptee may bias the studies with regard to the relative influence of genes and environment compared to the general population. The aim was to investigate whether the cohort of domestic adoptees used for these studies in Denmark is similar to the general population with respect to all-cause mortality and cause-specific mortality rates.

Methods

13,111 adoptees born in Denmark in 1917, or later, and adopted in 1924 to 1947 were compared to all Danes from the same birth cohorts using standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were similarly compared to all Danes using SMR as well as cause-specific SMR.

Results

The excess in all-cause mortality before age 65 years in adoptees was estimated to be 1.30 (95% CI 1.26–1.35). Significant excess mortality before age 65 years was also observed for infections, vascular deaths, cancer, alcohol-related deaths and suicide. Analyses including deaths after age 65 generally showed slightly less excess in mortality, but the excess was significant for all-cause mortality, cancer, alcohol-related deaths and suicides.

Conclusion

Adoptees have an increased all-cause mortality compared to the general population. All major specific causes of death contributed, and the highest excess is seen for alcohol-related deaths.     

All-Cause and Cause-Specific Mortality after Long-Term Sickness Absence for Psychiatric Disorders: A Prospective Cohort Study

Objective

The aim was to examine if long-term psychiatric sickness absence was associated with all-cause and diagnosis-specific (cardiovascular disease (CVD), cancer and suicide) mortality for the period 1990–2007. An additional aim was to examine these associations for psychiatric sickness absence in 1990 and 2000, with follow-up on mortality during 1991–1997 and 2001–2007, separately.

Methods

Employees within municipalities and county councils, 244,990 individuals in 1990 and 764,137 individuals in 2000, were followed up to 2007 through register linkages. Analyses were conducted with flexible parametric survival models comparing sickness absentees due to psychiatric diagnoses (>90 days) with those not receiving sick leave benefit.

Results

Long-term sickness absence for psychiatric disorders was associated with an increased risk of mortality due to all causes; CVD; cancer (smoking and non-smoking related); and suicide during the period 1990–2007. After full adjustment for socio-demographic covariates and previous inpatient care due to somatic and psychiatric diagnoses, these associations remained significant for all-cause mortality (Hazard ratios (HR) and 95% confidence interval (CI)): HR 1.56, 95% CI 1.3–1.8; CVD: HR 1.35, 95% CI 1.0–1.9, and suicide: HR 3.84, 95% CI 2.4–6.1. For both cohorts 1990 and 2000 estimates point in the same direction. For the time-period 2000–2007, we found increased risks of mortality in the fully adjusted model due to all causes: HR 1.47, 95% CI 1.2–1.7; CVD: HR 1.83, 95% CI 1.2–2.7; overall cancer: HR 1.33, 95% CI 1.0–1.7; and suicide: HR 2.15, 95% CI 1.3–3.7.

Conclusion

Long-term sickness absence for psychiatric disorders predicted premature mortality from all-causes, cardiovascular disease, cancer, and suicide.     

The Joint Effect of Sleep Duration and Disturbed Sleep on Cause-Specific Mortality: Results from the Whitehall II Cohort Study

Background

Both sleep duration and sleep quality are related to future health, but their combined effects on mortality are unsettled. We aimed to examine the individual and joint effects of sleep duration and sleep disturbances on cause-specific mortality in a large prospective cohort study.

Methods

We included 9,098 men and women free of pre-existing disease from the Whitehall II study, UK. Sleep measures were self-reported at baseline (1985–1988). Participants were followed until 2010 in a nationwide death register for total and cause-specific (cardiovascular disease, cancer and other) mortality.

Results

There were 804 deaths over a mean 22 year follow-up period. In men, short sleep (≤6 hrs/night) and disturbed sleep were not independently associated with CVD mortality, but there was an indication of higher risk among men who experienced both (HR = 1.57; 95% CI: 0.96–2.58). In women, short sleep and disturbed sleep were independently associated with CVD mortality, and women with both short and disturbed sleep experienced a much higher risk of CVD mortality (3.19; 1.52–6.72) compared to those who slept 7–8 hours with no sleep disturbances; equivalent to approximately 90 additional deaths per 100,000 person years. Sleep was not associated with death due to cancer or other causes.

Conclusion

Both short sleep and disturbed sleep are independent risk factors for CVD mortality in women and future studies on sleep may benefit from assessing disturbed sleep in addition to sleep duration in order to capture health-relevant features of inadequate sleep.     

Overweight and Class I Obesity Are Associated with Lower 10-Year Risk of Mortality in Brazilian Older Adults: The Bambuí Cohort Study of Ageing

Background

Prospective studies mostly with European and North-American populations have shown inconsistent results regarding the association of overweight/obesity and mortality in older adults. Our aim was to investigate the relationship between overweight/ obesity and mortality in an elderly Brazilian population.

Methods and Findings

Participants were 1,450 (90.2% from total) individuals aged 60 years and over from the community-based Bambuí (Brazil) Cohort Study of Ageing. From 1997 to 2007, 521 participants died and 89 were lost, leading to 12,905 person-years of observation. Body mass index (BMI) and waist circumference (WC) were assessed at baseline and at the 3rd and 5th years of follow-up. Multiple imputation was performed to deal with missing values. Hazard ratios (HR) of mortality for BMI or WC alone (continuous and categorical), and BMI and WC together (continuous) were estimated by extended Cox regression models, which were fitted for clinical, socioeconomic and behavioral confounders. Adjusted absolute rates of death at 10-year follow-up were estimated for the participants with complete data at baseline. Continuous BMI (HR 0.85; 95% CI 0.80–0.90) was inversely related to mortality, even after exclusion of smokers (HR 0.85; 0.80–0.90), and participants who had weight variation and died within the first 5 years of follow-up (HR 0.83; CI 95% 0.73–0.94). Overweight (BMI 25–30 kg/m²) was inversely (HR 0.76; 95%CI 0.61–0.93) and obesity (BMI ≥30 kg/m²; HR 0.85; 95% CI 0.64–1.14) not significantly associated with mortality. Subjects with BMI between 25–35 kg/m² (23.8–25.9%) had the lowest absolute rates of death at 10-years follow-up. The association between WC and death was not significant, except after adjusting WC for BMI levels, when the relationship turned into marginally positive (HR 1.01; CI 95% 1.00–1.02).

Conclusions

The usual BMI and WC cut-off points should not be used to guide public health and clinical weight control interventions in elderly in Brazil.     

Whole-Body CT in Haemodynamically Unstable Severely Injured Patients – A Retrospective,Multicentre Study

Background

The current common and dogmatic opinion is that whole-body computed tomography (WBCT) should not be performed in major trauma patients in shock. We aimed to assess whether WBCT during trauma-room treatment has any effect on the mortality of severely injured patients in shock.

Methods

In a retrospective multicenter cohort study involving 16719 adult blunt major trauma patients we compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90–110,<90 or >110 mmHg) at hospital admission and who received WBCT during resuscitation to those who did not. Using data derived from the 2002–2009 version of TraumaRegister®, we determined the observed and predicted mortality and calculated the standardized mortality ratio (SMR) as well as logistic regressions.

Findings

9233 (55.2%) of the 16719 patients received WBCT. The mean injury severity score was 28.8±12.1. The overall mortality rate was 17.4% (SMR  = 0.85, 95%CI 0.81–0.89) for patients with WBCT and 21.4% (SMR = 0.98, 95%CI 0.94–1.02) for those without WBCT (p<0.001). 4280 (25.6%) patients were in moderate shock and 1821 (10.9%) in severe shock. The mortality rate for patients in moderate shock with WBCT was 18.1% (SMR 0.85, CI95% 0.78–0.93) compared to 22.6% (SMR 1.03, CI95% 0.94–1.12) to those without WBCT (p<0.001, p = 0.002 for the SMRs). The mortality rate for patients in severe shock with WBCT was 42.1% (SMR 0.99, CI95% 0.92–1.06) compared to 54.9% (SMR 1.10, CI95% 1.02–1.16) to those without WBCT (p<0.001, p = 0.049 for the SMRs). Adjusted logistic regression analyses showed that WBCT is an independent predictor for survival that significantly increases the chance of survival in patients in moderate shock (OR = 0.73; 95%CI 0.60–0.90, p = 0.002) as well as in severe shock (OR = 0.67; 95%CI 0.52–0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock.

Conclusions

WBCT during trauma resuscitation significantly increased the survival in haemodynamically stable as well as in haemodynamically unstable major trauma patients. Thus, the application of WBCT in haemodynamically unstable severely injured patients seems to be safe, feasible and justified if performed quickly within a well-structured environment and by a well-organized trauma team.     

Trends in Severity of Illness on ICU Admission and Mortality among the Elderly

Background

There is an increase in admission rate for elderly patients to the ICU. Mortality rates are lower when more liberal ICU admission threshold are compared to more restrictive threshold. We sought to describe the temporal trends in elderly admissions and outcomes in a tertiary hospital before and after the addition of an 8-bed medical ICU.

Methods

We conducted a retrospective analysis of a comprehensive longitudinal ICU database, from a large tertiary medical center, examining trends in patients’ characteristics, severity of illness, intensity of care and mortality rates over the years 2001–2008. The study population consisted of elderly patients and the primary endpoints were 28 day and one year mortality from ICU admission.

Results

Between the years 2001 and 2008, 7,265 elderly patients had 8,916 admissions to ICU. The rate of admission to the ICU increased by 5.6% per year. After an eight bed MICU was added, the severity of disease on ICU admission dropped significantly and crude mortality rates decreased thereafter. Adjusting for severity of disease on presentation, there was a decreased mortality at 28- days but no improvement in one- year survival rates for elderly patient admitted to the ICU over the years of observation. Hospital mortality rates have been unchanged from 2001 through 2008.

Conclusion

In a high capacity ICU bed hospital, there was a temporal decrease in severity of disease on ICU admission, more so after the addition of additional medical ICU beds. While crude mortality rates decreased over the study period, adjusted one-year survival in ICU survivors did not change with the addition of ICU beds. These findings suggest that outcome in critically ill elderly patients may not be influenced by ICU admission. Adding additional ICU beds to deal with the increasing age of the population may therefore not be effective.     

Statins and Hip Fracture Prevention – A Population Based Cohort Study in Women

Objective

To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women.

Design

A register-based cohort study.

Setting

Finland.

Participants

Women aged 45–75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥80% during the subsequent five years (n = 40 254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585).

Main Outcome Measures

Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period.

Results

Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157 090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58–0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55–0.87). When women with poor (<40%), moderate (40 to 80%), and good adherence (≥80%) to statins were compared to those with good adherence to hypertension drugs (≥80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence.

Conclusions

5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50–80 years without prior hospitalizations for fractures.     

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.     

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Background

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods

We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results

During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1).

Conclusion

Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.     

Impact of a Partial Smoke-Free Legislation on Myocardial Infarction Incidence,Mortality and Case-Fatality in a Population-Based Registry: The REGICOR Study

Background and Objective

Coronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain.

Methods

Using a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002–2005 and 2006–2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban''s impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA).

Results

In the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81–0.97 and RR = 0.82; 95% CI = 0.71–0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65–74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition.

Conclusions

The 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65–74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD.     

Serum Potassium Levels and Its Variability in Incident Peritoneal Dialysis Patients: Associations with Mortality

Background

Abnormal serum potassium is associated with an increased risk of mortality in dialysis patients. However, the impacts of serum potassium levels on short- and long-term mortality and association of potassium variability with death in peritoneal dialysis (PD) patients are uncertain.

Methods

We examined mortality-predictability of serum potassium at baseline and its variability in PD patients treated in our center January 2006 through December 2010 with follow-up through December 2012. The hazard ratios (HRs) were used to assess the relationship between baseline potassium levels and short-term (≤1 year) as well as long-term (>1 year) survival. Variability of serum potassium was defined as the coefficient of variation of serum potassium (CVSP) during the first year of PD.

Results

A total of 886 incident PD patients were enrolled, with 248 patients (27.9%) presented hypokalemia (serum potassium <3.5 mEq/L). During a median follow-up of 31 months (range: 0.5–81.0 months), adjusted all-cause mortality hazard ratio (HR) and 95% confidence interval (CI) for baseline serum potassium of <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.5 to <5.0, and ≥5.0 mEq/L, compared with 4.0 to <4.5 (reference), were 1.79 (1.02–3.14), 1.15 (0.72–1.86), 1.31 (0.82–2.08), 1.33 (0.71–2.48), 1.28 (0.53–3.10), respectively. The increased risk of lower potassium with mortality was evident during the first year of follow-up, but vanished thereafter. Adjusted all-cause mortality HR for CVSP increments of 7.5% to <12.0%; 12.0% to <16.7% and ≥16.7%, compared with <7.5% (reference), were 1.35 (0.67–2.71), 2.00 (1.05–3.83) and 2.18 (1.18–4.05), respectively. Similar association was found between serum potassium levels and its variability and cardiovascular mortality.

Conclusions

A lower serum potassium level was associated with all-cause and cardiovascular mortality during the first year of follow-up in incident PD patients. In addition, higher variability of serum potassium levels conferred an increased risk of death in this population.     

The Relationship between Total Bilirubin Levels and Total Mortality in Older Adults: The United States National Health and Nutrition Examination Survey (NHANES) 1999-2004

Objective

Due to its anti-oxidant and anti-inflammatory properties, bilirubin has been associated with reduced cardiovascular risk. A recent study demonstrated an L-shaped association of pre-treatment total bilirubin levels with total mortality in a statin-treated cohort. We therefore investigated the association of total bilirubin levels with total mortality in a nationally representative sample of older adults from the general population.

Methods

A total of 4,303 participants aged ≥60 years from the United States National Health and Nutrition Examination Survey 1999–2004 with mortality data followed up through December 31, 2006 were included in this analysis, with a mean follow-up period of 4.5 years.

Results

Participants with total bilirubin levels of 0.1–0.4 mg/dl had the highest mortality rate (19.8%). Compared with participants with total bilirubin levels of 0.5–0.7 mg/dl and in a multivariable regression model, a lower total bilirubin level of 0.1–0.4 mg/dl was associated with higher risk of total mortality (hazard ratios, 1.36; 95% confidence interval, 1.07–1.72; P = 0.012), while higher levels (≥0.8 mg/dl) also tended to be associated with higher risk of total mortality, but this did not reach statistical significance (hazard ratios, 1.24; 95% confidence interval, 0.98–1.56; P = 0.072).

Conclusion

In this nationally representative sample of older adults, the association of total bilirubin levels with total mortality was the highest among those with a level between 0.1 and 0.4 mg/dl. Further studies are needed to investigate whether higher total bilirubin levels could be associated with a higher mortality risk, compared to a level of 0.5–0.7 mg/dl.