Absolute Mortality Differences Research Articles

Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.

The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. Adult patients presenting to the emergency department with severe sepsis or septic shock. EGDT vs. usual care. A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

Diabetes and all-cause mortality among middle-aged and older adults in China, England, Mexico, rural South Africa, and the United States: A population-based study of longitudinal aging cohorts.

There is a need for comparable worldwide data on the impact of diabetes on mortality. This study assessed diabetes and all-cause mortality among middle-aged and older adults in five countries. We analyzed adults aged 51 years or older followed between 2010 and 2020 from population-based cohorts in China, England, Mexico, rural South Africa, and the United States. Diabetes was defined by self-report or an elevated diabetes blood-based biomarker meeting the clinical criteria for diabetes. All-cause mortality was assessed through linkages or informant interviews. We used Poisson regression models to estimate mortality rate ratios and mortality rate differences, comparing people with diabetes to those without diabetes. Models were adjusted for age, gender, education, smoking status, body mass index, and economic status. We included 29,397 individuals, of whom 4,916 (16.7%) died during the study period. The median follow-up time ranged from 4.6 years in South Africa to 8.3 years in China. The adjusted all-cause mortality rate ratios for people with diabetes versus those without diabetes ranged from 1.53 (95% CI: 1.39-1.68) in the United States to 2.02 (95% CI: 1.34-3.06) in Mexico. The adjusted mortality rate differences (per 1,000 person-years) for people with diabetes versus those without diabetes ranged from 11.9 (95% CI: 4.8-18.9) in England to 24.6 (95% CI: 12.2-37.0) in South Africa. Diabetes was associated with increased all-cause mortality in population-based cohorts across five diverse countries. There is an urgent need to implement clinical and public health interventions to improve diabetes outcomes globally. Why did we undertake this study?: We aimed to address the need for comparable estimates of all-cause mortality among people with diabetes in diverse global settings.What is the specific question(s) we wanted to answer?: How does diabetes impact all-cause mortality among middle-aged and older adults (aged 51 years or greater) in China, England, Mexico, rural South Africa, and the United States?What did we find?: Middle-aged and older adults with diabetes had higher all-cause mortality than people without diabetes in all countries. Relative mortality differences ranged from mortality rate ratios of 1.53 in the United States to 2.02 in Mexico. Absolute mortality differences ranged from mortality rate differences (per 1,000 person-years) of 11.9 in England to 24.6 in South Africa.What are the implications of our findings?: There is an urgent need to implement clinical and public health interventions to improve diabetes outcomes globally.

Proximal vs Extensive Repair in Acute Type A Aortic Dissection Surgery

BackgroundThis purpose of this study was to evaluate the impact of proximal vs extensive repair on mortality and how this impact is influenced by patient characteristics. MethodsOf 5510 patients with acute type A aortic dissection from 13 Chinese hospitals (2016-2021) categorized by proximal vs extensive repair, 4038 patients were used for for model derivation using eXtreme gradient boosting and 1472 patients for model validation. ResultsOperative mortality of extensive repair was higher than proximal repair (10.4% vs 2.9%; odd ratio [OR], 3.833; 95% CI, 2.810-5.229; P < .001) with a number needed to harm of 15 (95% CI, 13-19). Seven top features of importance were selected to develop an alphabet risk model (age, body mass index, platelet-to-leucocyte ratio, albumin, hemoglobin, serum creatinine, and preoperative malperfusion), with an area under the curve of 0.767 (95% CI, 0.733-0.800) and 0.727 (95% CI, 0.689-0.764) in the derivation and validation cohorts, respectively. The absolute rate differences in mortality between the 2 repair strategies increased progressively as predicted risk rose; however it did not become statistically significant until the predicted risk exceeded 4.5%. Extensive repair was associated with similar risk of mortality (OR, 2.540; 95% CI, 0.944-6.831) for patients with a risk probability < 4.5% but higher risk (OR, 2.164; 95% CI, 1.679-2.788) for patients with a risk probability > 4.5% compared with proximal repair. ConclusionsExtensive repair is associated with higher mortality than proximal repair; however it did not carry a significantly higher risk of mortality until the predicted probability exceeded a certain threshold. Choosing the right surgery should be based on individualized risk prediction and treatment effect. (ClinicalTrials.gov no. NCT04918108.)

Cognition and Mortality Risk Among Midlife and Older Americans.

Cognitive impairment is associated with increased mortality rates in late life, but it is unclear whether worse cognition predicts working-age mortality. The data come from a U.S.national survey (N=3973 aged 32-84 at cognitive testing in 2004-06, mean age 56.6, 56.3% female; N=3055 retested in 2013-18 at ages 42-94, mean age 64.6, 56.6% female; mortality follow-up through 2019). We use Cox hazard models to investigate whether cognition is associated with mortality below age 65, how the magnitude of this risk compares with the risk in later life, and whether the association persists after adjusting for potential confounders. Worse cognition is associated with mortality, but the demographic-adjusted hazard ratio (HR) diminishes with age from 2.0 per standard deviation (SD; 95% confidence interval [CI], 1.7-2.4) at age 55-1.4 (95% CI, 1.3-1.6) at age 85. In the fully adjusted model, the corresponding HRs are 1.4 (95% CI, 1.2-1.7) and 1.3 (95% CI, 1.1-1.4), respectively. The absolute differences in mortality by level of cognition, however, are larger at older ages because mortality is rare at younger ages. The fully adjusted model implies a 2.7 percentage point differential in the estimated percentage dying between ages 55 and 65 for those with low cognition (1 SD below the overall mean, 5.7%) versus high cognition (1 SD above the mean, 3.0%). The corresponding differential between ages 75 and 85 is 8.4 percentage points (24.6% vs 16.2%, respectively). Cognitive function may be a valuable early warning sign of premature mortality, even at working ages, when dementia is rare.

Parental income gradients in child and adolescent mortality: Norwegian trends over half a century.

Child mortality has declined rapidly over the last century in many high-income countries. However, little is known about the socio-economic differences in this decline and whether these vary across causes of death. We used register data that included all Norwegian births between 1968 and 2010 (2.1 million), and we analysed how all-cause and cause-specific child (0-4 years) and adolescent (5-20 years) mortality rates vary with relative parental income the year before the birth. Child and adolescent all-cause mortality decreased with increasing parental relative income within all birth cohorts. Among children aged 0-4 years, the socio-economic gradient in all-cause mortality and in mortality due to external causes, sudden infant deaths and perinatal factors declined over the period, while there was no systematic decline in mortality from congenital malformations. Among children aged 5-20 years, the gradient did not weaken similarly, although there were indications of declines in the socio-economic gradient related to all-cause deaths and deaths because of suicides and other external causes. While the absolute differences in mortality declined over time, the relative differences remained stable. Although children of low-income parents still have elevated mortality, there has been a large reduction in child mortality in all socio-economic groups across 50 years for all causes combined and most of the groups of specific causes of death.

The income-mortality paradox among first- and second-generation immigrants in Sweden

Abstract Background This study investigates mortality differences by income among first- and second-generation immigrants and the native ancestral population in Sweden. Despite immigrants’ various vulnerabilities and the exhaustive evidence for a persistent inverse relationship between income and mortality in general Western populations, previous studies from outside Sweden demonstrated surprisingly weak income gradients in mortality among first-generation immigrants. Examining these associations among second-generation immigrants may help to understand this paradox. Methods Swedish register data from 2002 to 2016 were used to study the association between individual income rank positions and all-cause mortality. The study population was restricted to ages 25-64 years. Based on ‘relative indices of inequality’ (RII) derived from Poisson regressions, we measured mortality differentials between the least and most deprived income rank positions stratified by nativity group and sex. Correspondingly, we assessed absolute differences in mortality between the most and least deprived by using ‘slope indices of inequality’ (SII). Results Largest inequalities in mortality by relative income rank positions (based on RII) were found for the Swedish native ancestral population that showed on average a nearly doubled mortality risk for least compared to most deprived rank position. Immigrants disclosed weak or even nullified associations between relative income rank and all-cause mortality. Mortality inequalities by income among second-generation immigrants were substantially higher relative to first-generation immigrants but somewhat lower compared to the native ancestral population. These patterns were consistent between males and females, and confirmed by the use of SII. Conclusions Distinct exposures to inequality structures but also first-generation immigrants’ ‘mortality advantage’ likely contribute to the considerable mortality differences by income between the studied nativity groups. Key messages • Despite their social and economic vulnerabilities, first-generation immigrants in Sweden disclose weak associations between relative income rank and all-cause mortality. • Second-generation immigrants in Sweden show notably higher magnitudes in income-related mortality compared with first-generation immigrants.

A longitudinal study of how disability has affected survival in Swedish populations across 150 years

Abstract Background Studies from across the world report that disability jeopardizes people's health and increases the risk of premature death. The trend has been demonstrated in present-day populations but there has been little research about whether disability affected survival in historical populations. Our objective was to identify long-term developments in the relationship between disability and survival. Methods We focused on all causes of mortality in ages 25-42 among groups with any type of disability in Swedish populations in the 1800s, 1900s and 2000s. We used Cox proportional regression and longitudinal micro-level data, measuring both relative differences (HRs) and absolute differences (excess LYL) in premature mortality, across time by disability status and sex. Results Although the overall mortality declined profoundly in Sweden during the centuries studied, the strong association between disability and premature mortality persisted, generating a significant disability-survival gap that has held since the 1800s. The absolute difference in this gap narrowed only slightly during the 1900s, from excess LYL due to disability for men of 1.67 (CI 0.17-3.44) in the 1800s, to 0.69 (CI 0.54-0.85) in the 2000s, while for women the change was even smaller, from 1.24 (CI -0.46-3.12) to 0.59 (CI 0.43-0.69). However, the relative difference widened, particularly for women, from HR of 2.46 (CI 0.91-6.70) in the 1800s to HR 12.00 (CI 9.88-14.60) in the 2000s. For men we found a change in HR from 2.30 (CI 1.31-4.06) to 8.48 (CI 7.26-9.92). Conclusions Our study is unique in providing comprehensive results about how disability has limited survival for more than 150 years. In Sweden, fundamental societal changes and extensive welfare provisions promoting equality in health and social wellbeing of all citizens have not been enough to improve the survival of younger generations with disabilities. Key messages • The strong association between disability and premature mortality persisted from the 1800s to the 2000s. • In Sweden, fundamental societal changes and extensive welfare provisions promoting equality in health have not improved survival of young adults with disabilities.

Quantifying the contribution of established risk factors to cardiovascular mortality differences between Russia and Norway

Surprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40–69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1–40.1) among men and 22.1% (10.4–31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9–10 to 7–8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.

Contrasts in alcohol-related mortality in Czechia and Lithuania: Analysis of time trends and educational differences.

Introduction and Aims. Globally, Czechia and Lithuania are among the top‐ranking countries in terms of high alcohol consumption. This study highlights notable contrasts in temporal trends in alcohol‐related mortality and identifies country‐specific patterns in educational differences. Design and Methods. The study uses harmonised cause‐of‐death series from the Human Cause of Death Database. Mortality disparities by education were assessed using census‐linked mortality data. Directly standardised death rates were used to estimate levels of national and group‐specific mortality. Relative and absolute mortality differences by education were assessed by range‐type measures (Poisson regression mortality ratios and rate differences) and Gini‐type measures. Results. Between 1994–1995 and 2016, the absolute difference between Czechia and Lithuania in terms of alcohol‐related age‐standardised death rates (per 1 000 000) decreased from 450 for males and 130 for females to 76 in males and 11 in females. In both countries, alcohol‐related mortality was markedly higher among persons of lower education levels. Lithuanian males experienced the highest absolute inequalities measured by rate difference between the low and high educated (740 per million), while Lithuanian females showed the most pronounced relative inequalities (6.70‐fold difference between low and high educated). The corresponding figures were less than half for Czechia. Discussion and Conclusions. Reducing educational disparities in alcohol‐related mortality within both countries would have a substantial impact on overall levels. Policies aimed at targeting the lowest priced and illegal alcohols and reducing levels of harmful drinking should be a priority, especially in Lithuania.

Dexamethasone in Hospitalized Patients with Covid-19

BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)

Apgar Score and Risk of Neonatal Death among Preterm Infants

BackgroundGestational age is the major determinant of neonatal death (death within the first 28 days of life) in preterm infants. The joint effect of gestational age and Apgar score on the risk of neonatal death is unknown.MethodsUsing data from the Swedish Medical Birth Register, we identified 113,300 preterm infants (22 weeks 0 days to 36 weeks 6 days of gestation) born from 1992 through 2016. In analyses stratified according to gestational age (22 to 24 weeks, 25 to 27 weeks, 28 to 31 weeks, 32 to 34 weeks, and 35 or 36 weeks), we estimated adjusted relative risks of neonatal death and absolute rate differences in neonatal mortality (i.e., the excess number of neonatal deaths per 100 births) according to the Apgar scores at 5 and 10 minutes and according to the change in the Apgar score between 5 minutes and 10 minutes. Scores range from 0 to 10, with higher scores indicating a better physical condition of the newborn.ResultsThere were 1986 neonatal deaths (1.8%). The incidence of neonatal death ranged from 0.2% (at 36 weeks of gestation) to 76.5% (at 22 weeks of gestation). Lower Apgar scores were associated with higher relative risks of neonatal death and greater absolute rate differences in neonatal mortality in all gestational-age strata. For example, among infants born at 28 to 31 weeks, the adjusted absolute rate differences according to the 5-minute Apgar score, with those who had a score of 9 or 10 serving as the reference group, were 51.7 (95% confidence interval [CI], 38.1 to 65.4) for a score of 0 or 1, 25.5 (95% CI, 18.3 to 32.8) for a score of 2 or 3, 7.1 (95% CI, 5.1 to 9.1) for a score of 4 to 6, and 1.2 (95% CI, 0.5 to 1.9) for a score of 7 or 8. An increase in the Apgar score between 5 minutes and 10 minutes was associated with lower neonatal mortality than a stable Apgar score.ConclusionsIn this study, Apgar scores at 5 and 10 minutes provided prognostic information about neonatal survival among preterm infants across gestational-age strata. (Funded by the Swedish Research Council for Health, Working Life, and Welfare and Karolinska Institutet.)

Abstract P439: Generalizability of Heterogeneous Treatment Effects of Intensive Glycemic Control on All-cause Mortality Across Two Randomized Trials

Background: Machine learning is an attractive tool for identifying patient subgroups that exhibit heterogeneous treatment effects (HTE) of an intervention. Whether HTE identified using machine learning methods generalize across clinical studies is unclear. Prior work using a causal forest machine learning approach identified hemoglobin glycation index (HGI), body mass index (BMI), and age as determinants of HTE of intensive versus standard glycemic control on all-cause mortality in the ACCORD randomized trial. We examined whether the same three variables defined HTE in the VA Diabetes Trial (VADT), an independent randomized trial of intensive versus standard glycemic control in type 2 diabetes patients. Methods: The VADT study randomized participants to intensive (median hemoglobin A1c [HbA1c] achieved of 6.9%) or standard (median HbA1c achieved of 8.4%) glycemic control. In this secondary analysis comparing results with the ACCORD trial, we included 1789 out of 1791 VADT participants who had non-missing data at baseline for fasting glucose, HbA1c, BMI, age, and lab values and comorbidities included in prior machine learning analysis of the ACCORD trial; median follow-up was 5.6 years. We examined the absolute risk difference in all-cause mortality in four subgroups with HTE for mortality in the ACCORD trial: group 1, HGI &lt; 0.44, BMI &lt; 30kg/m 2 , Age &lt; 61 years; group 2, HGI &lt; 0.44, BMI &lt; 30kg/m 2 , Age ≥ 61 years; group 3, HGI &lt; 0.44, BMI ≥ 30kg/m 2 ; and group 4, HGI ≥ 0.44. We repeated the analysis after using inverse odds of sampling weights to standardize VADT study participants to the ACCORD study participants using individual-level data from both studies. Methods: The absolute all-cause mortality difference between intensive and standard glycemic control in all VADT participants included in this study was 0.8%. The absolute mortality difference did not vary significantly across subgroups: 2.2% (95% CI -6.0, 10) in group 1 (n=140), 3.4% (-7.3, 14.2) in group 2 (n=192), 2.4% (-2.9, 7.7) in group 3 (n=517), and -0.8% (-4.8, 3.1) in group 4 (n=940), where negative values indicate lower mortality in the intensive glycemic control intervention arm. The absolute mortality differences for the corresponding subgroups in the ACCORD trial were: -2.3% (-4.3, -0.2), 0.7% (-1.6, 3.1), 0.9% (0.4, 2.1), 3.7% (1.5, 6.0) in groups 1, 2, 3, and 4 respectively. The pattern of absolute mortality differences across groups 1 through 4 in the ACCORD study did not reproduce in the VADT study even after standardization of study population characteristics with the ACCORD study. Conclusions: Machine learning methods to define HTE subgroups from randomized trials may not be generalizable across study samples and are likely sensitive to variability in the intervention and differences in study populations. Additional work is needed to define consistent HTE that can guide individualized diabetes treatment.

Migrant mortality differences in the 2000s in Belgium: interaction with gender and the role of socioeconomic position

BackgroundBelgium has a long history of migration. As the migrant population is ageing, it is crucial thoroughly to document their health. Many studies that have assessed this, observed a migrant mortality advantage. This study will extend the knowledge by probing into the interaction between migrant mortality and gender, and to assess the role of socioeconomic position indicators in this paradox.MethodsIndividually linked data of the 2001 Belgian Census, the National Register and death certificates for 2001–2011 were used. Migrant origin was based on both own and parents’ origin roots. We included native Belgians and migrants from the largest migrant groups aged 25 to 65 years. Absolute and relative mortality differences by migrant origin were calculated for the most common causes of death. Moreover, the Poisson models were adjusted for educational attainment, home ownership and employment status.ResultsWe observed a migrant mortality advantage for most causes of death and migrant groups, which was strongest among men. Adjusting for socioeconomic position generally increased the migrant mortality advantage, however with large differences by gender, migrant origin, socioeconomic position indicator and causes of death.ConclusionsAdjusting for socioeconomic position even accentuated the migrant mortality advantage although the impact varied by causes of death, migrant origin and gender. This highlights the importance of including multiple socioeconomic position indicators when studying mortality inequalities. Future studies should unravel morbidity patterns too since lower mortality not necessarily implies better health. The observed migrant mortality advantage suggests there is room for improvement. However, it is essential to organize preventative and curative healthcare that is equally accessible across social and cultural strata.

Trends in Belgian cause-specific mortality by migrant origin between the 1990s and the 2000s

BackgroundBelgium has a large migrant community that is increasingly ageing. As migrants may have faced environmental and social exposures before, during and after migration, they may have experienced an accelerated epidemiological transition. Studying mortality differentials between the migrant and native population may therefore allow for a better understanding of the aetiology of diseases. While many studies have assessed migrant mortality, few have looked into the role of gender or the trend over time. Therefore, this study aims to probe into mortality differences between the native and migrant population for all major causes of death (COD) during the 1990s and 2000s. We will discriminate between all major migrant groups and men and women as they have different migration histories.MethodsIndividually linked data of the Belgian Census, the National Register and death certificates for the periods 1991–1997 and 2001–2008 were used. Migrant origin was based on both own and parents’ origin, hereby maximizing the population with migrant roots. We included native Belgians and migrants from the largest migrant groups aged 25 to 65 years. Both absolute and relative mortality differences by migrant origin were calculated for the most common COD.ResultsWe generally observed a migrant advantage for overall, cause-specific and cancer-specific mortality, with infection-related cancer mortality being the only exception. The effect was particularly strong for lifestyle-related COD, non-western migrants, and men. Over time, mortality declined among native Belgian men and women, yet remained stable for several migrant groups. This converging trend was largely due to smoking and reduced reproductive behaviour among migrants.ConclusionsThe migrant mortality advantage stresses that there is room for improvement in the area of health in Belgium. Since the largest differences between native Belgians and migrants were observed for lifestyle-related diseases, and there is a tendency towards convergence of mortality over time, primary prevention tackling the most vulnerable groups remains crucial. Moreover, efforts should be made to ensure equal access to health care among the social and cultural strata.

Analysis of Benefit of Intensive Care Unit Transfer for Deteriorating Ward Patients

It is unknown which deteriorating ward patients benefit from intensive care unit (ICU) transfer. To use an instrumental variable (IV) method that assesses heterogeneity and to evaluate estimates of person-centered treatment effects of ICU transfer and 28-day hospital mortality by age and illness severity. An analysis of a prospective cohort study from November 1, 2010, to December 31, 2011. The dates of this analysis were June 1, 2017, to June 30, 2018. The setting was a multicenter study of 49 UK National Health Service hospitals. Participants were 9192 deteriorating ward patients assessed for ICU transfer (4596 matched pairs). The study matched on baseline characteristics to strengthen the IV and to balance observed confounders between the comparison groups. Transfer to the ICU or continued care on general wards. Mortality at 28 days (primary outcome) and 90 days. To address unobserved confounding, ICU bed availability was the IV for whether or not a patient was transferred. The study used the IV approach to evaluate estimates of treatment effect of ICU transfer and mortality according to age and physiological severity alone and in combination. Both comparison groups included 4596 patients. In the group assessed with "many" ICU beds available (median, 7), 52.8% were male, and the mean (SD) age was 65.2 (17.7) years; in the group assessed with "few" ICU beds available (median, 2), 53.3% were male, and the mean (SD) age was 65.0 (17.3) years. The overall 28-day mortality estimates were 23.2% (2090 predicted deaths) if all of the matched patients were transferred vs 28.1% (2534 predicted deaths) if none of the matched patients were transferred, an estimated risk difference of -4.9% (95% CI, -26.4% to 16.6%). The estimated effects of ICU transfer differed by age and by physiological severity according to the National Early Warning Score (NEWS): the absolute risk differences in 28-day mortality after ICU transfer ranged from 7.7% (95% CI, -5.5% to 21.0%) for ages 18 to 23 years to -5.0% (95% CI -26.5% to 16.6%) for age 78 to 83 years and ranged from 3.7% (95% CI, -12.1% to 19.5%) for NEWS of 0 to -25.4% (95% CI, -50.6% to -0.2%) for NEWS of 19. The absolute risk differences for elderly patients (≥75 years) were -11.6% (95% CI, -39.0% to 15.8%) for those with high NEWS (>6), -4.8% (95% CI, -30.5% to 20.9%) for those with moderate NEWS (5-6), and -1.0% (95% CI, -24.8% to 22.8%) for those with low NEWS (<5). The corresponding estimates for subgroups of younger patients (<75 years) were -8.4% (95% CI, -31.0% to 14.1%), -2.1% (95% CI, -21.1% to 16.9%), and 1.4% (95% CI, -14.5% to 17.4%). This study using a this person-centered IV approach found that the benefits of ICU care may increase among patients at high levels of baseline physiological severity across different age groups, especially among elderly patients.

Sex differences in the 1-year risk of dying following all-cause and cause-specific hospital admission after age 50 in comparison with a general and non-hospitalised population: a register-based cohort study of the Danish population

ObjectivesWe examine the mortality of men and women within the first year after all-cause and cause-specific hospital admission to investigate whether the sex differences in mortality after hospitalisation are higher...

Unchanging premature mortality trends in systemic lupus erythematosus: a general population-based study (1999-2014).

Patients with SLE have increased morbidity and premature mortality. Whether this mortality gap has improved in recent years, as in RA, is unknown. We conducted a population-based cohort study using a medical records database representative of the general population of the UK. We identified incident SLE cases and matched non-SLE controls between 1999 and 2014, divided into two subgroups based on year of SLE diagnosis, forming the early cohort (1999-2006) and late cohort (2007-14). We compared the mortality rates and hazard ratios, adjusting for potential confounders. We identified 1470 and 1666 incident SLE cases in the early and late cohorts, respectively. In both cohorts, SLE patients had similar levels of excess mortality compared with their matched comparators [15.9 vs 7.9 deaths/1000 person-years (PY) in the early cohort and 13.8 vs 7.0 deaths/1000 PY in the late cohort]. The corresponding mortality hazard ratios were 2.15 (95% CI 1.63, 2.83) and 2.12 (95% CI 1.61, 2.80) in the early and late cohorts, respectively (P-value for interaction = 0.95). The absolute mortality differences were 8.0 (95% CI 4.3, 11.8) and 6.8 (95% CI 3.5, 10.0) deaths/1000 PY, respectively (P-value for interaction = 0.61). This general population-based cohort study suggests that excess mortality has not improved among SLE patients in recent years, remaining greater than double that of comparators, unlike RA during the same period. This highlights a critical unmet need for the development of new therapeutic agents and improved management strategies for SLE and its comorbidities.

Underestimated Health Inequalities Among Older People-A Consequence of Excluding the Most Disabled and Disadvantaged.

The present study analyzed whether estimates of health inequalities in old age are sensitive to the exclusion of people living in institutions and nonuse of proxy interviews. Pooled data from the 2004 wave (n = 1,180, aged 69-100, primarily interviewed over the phone) and the 2011 wave (n = 931, aged 76-101, primarily interviewed face-to-face) of the Swedish Panel Study of Living Conditions of the Oldest Old were used to compare absolute and relative differences in disability and mortality between people with compulsory education and people with more than compulsory education. Both absolute and relative health inequalities would have been underestimated in a survey that excluded institutionalized people and proxy-interviewed community dwellers. The same patterns were found in men and women and regardless of the mode of data collection (telephone or face-to-face interview). The degree of underestimation was lower in those 85 years and older than in those 69 to 84 years. A survey that only includes people who live in the community and can participate without the help of a proxy might give the impression that those with low levels of education have less extensive health disadvantages than they actually have.

Trends of relative and absolute socioeconomic equity in access to coronary revascularisations in 1995\u20132010 in Finland: a register study

BackgroundResources for coronary revascularisations have increased substantially since the early 1990s in Finland. At the same time, ischaemic heart disease (IHD) mortality has decreased markedly. This study aims to examine how these changes have influenced trends in absolute and relative differences between socioeconomic groups in revascularisations and age group differences in them using IHD mortality as a proxy for need.MethodsHospital Discharge Register data on revascularisations among Finns aged 45–84 in 1995–2010 were individually linked to population registers to obtain socio-demographic data. We measured absolute and relative income group differences in revascularisation and IHD mortality with slope index of inequality (SII) and concentration index (C), and relative equity taking need for care into account with horizontal inequity index (HII).ResultsThe supply of procedures doubled during the years. Socioeconomic distribution of revascularisations was in absolute and relative terms equal in 1995 (Men: SII = −12, C = −0.00; Women, SII = −30, C = −0.03), but differences favouring low-income groups emerged by 2010 (M: SII = −340, C = −0.08; W: SII = −195, C = −0.14). IHD mortality decreased markedly, but absolute and relative differences favouring the better-off existed throughout study years. Absolute differences decreased somewhat (M: SII = −760 in 1995, SII = −681 in 2010; W: SII = −318 in 1995, SII = −211 in 2010), but relative differences increased significantly (M: C = −0.14 in 1995, C = −0.26 in 2010; W: C = −0.15 in 1995, C = −0.25 in 2010). HII was greater than zero in each year indicating inequity favouring the better-off. HII increased from 0.15 to 0.18 among men and from 0.10 to 0.12 among women. We found significant and increasing age group differences in HII.ConclusionsDespite large increase in supply of revascularisations and decrease in IHD mortality, there is still marked socioeconomic inequity in revascularisations in Finland. However, since changes in absolute distributions of both supply and need for coronary care have favoured low-income groups, absolute inequity can be claimed to have decreased although it cannot be quantified numerically.

Changing patterns of breast cancer incidence and mortality by education level over four decades in Norway, 1971-2009.

In the last century, breast cancer incidence and mortality was higher among higher versus lower educated women in developed countries. Post-millennium, incidence rates have flattened off and mortality declined. We examined breast cancer trends by education level, to see whether recent improvements in incidence and mortality rates have occurred in all education groups. We linked individual registry data on female Norwegian inhabitants aged 35 years and over during 1971–2009. Using Poisson models, we calculated absolute and relative educational differences in age-standardised breast cancer incidence and mortality over four decades. We estimated educational differences by Slope and Relative Index of Inequality, which correspond to rate difference and rate ratio, comparing the highest to lowest educated women. Pre-millennium, incidence and mortality of breast cancer were significantly higher in higher versus lower educated women. Post-millennium, educational differences in breast cancer incidence and mortality attenuated. During 2000–2009, breast cancer incidence was still 38% higher for higher versus lower educated women (Relative Index of Inequality: 1.38, 95% confidence interval: 1.31–1.44), but mortality no longer varied significantly by education level (Relative Index of Inequality: 1.09, 95% confidence interval: 0.99–1.19). Among women below 50 years, however, the education gradient for mortality reversed, and mortality was 28% lower for the highest versus lowest educated women during 2000–2009 (Relative Index of Inequality: 0.72, 95% confidence interval: 0.51–0.93). Post-millennium improvements in breast cancer incidence and mortality have primarily benefited higher educated women. Breast cancer mortality is now highest among the lowest educated women below 50 years.