Systemic autoimmune disease as a cause of death: mortality burden and comorbidities.

OBJECTIVES: Systemic autoimmune diseases (SAIDs) have chronic trajectories and share characteristics of self-directed inflammation, as well as aspects of clinical expression. Nonetheless, burden-of-disease studies rarely investigate them as a distinct category. This study aims to assess the mortality rate of SAIDs as a group and to evaluate co-occurring causes of death. METHODS: We used death certificate data in the Netherlands, 2013-2017 (N = 711 247), and constructed a SAIDs list at the fourth-position ICD-10 level. The mortality rate of SAIDs as underlying cause of death (CoD), non-underlying CoD, and any-mention CoD was calculated. We estimated age-sex-standardized observed/expected (O/E) ratios to assess comorbidities in deaths with SAID relative to the general deceased population. RESULTS: We observed 3335 deaths with SAID on their death certificate (0.47% of all deaths). The mortality rate of SAID was 14.6 per million population as underlying CoD, 28.0 as non-underlying CoD, and 39.7 as any-mention CoD. The mortality rate was higher for females and increased exponentially with age. SAID-related deaths were positively associated with all comorbidities except for solid neoplasms and mental conditions. Particularly strong was the association with diseases of the musculoskeletal system (O/E = 3.38; 95% CI: 2.98, 3.82), other diseases of the genitourinary system (O/E = 2.73; 95% CI: 2.18, 3.38), influenza (O/E = 2.71; 95% CI: 1.74, 4.03), blood diseases (O/E = 2.02; 95% CI: 1.70, 2.39), skin and subcutaneous tissue diseases (O/E = 1.95; 95% CI: 1.54, 2.45), and infectious diseases (O/E = 1.85; 95% CI: 1.70, 2.01). CONCLUSION: Systemic autoimmune diseases constitute a rare group of causes of death, but contribute to mortality through multiple comorbidities. Classification systems could be adapted to better encompass these diseases as a category.

How large should a cause of death be in order to be included in mortality trend analysis? Deriving a cut-off point from retrospective trend analyses in 21 European countries.

OBJECTIVES: The International Classification of Diseases (ICD-10) distinguishes a large number of causes of death (CODs) that could each be studied individually when monitoring time-trends. We aimed to develop recommendations for using the size of CODs as a criterion for their inclusion in long-term trend analysis. DESIGN: Retrospective trend analysis. SETTING: 21 European countries of the WHO Mortality Database. PARTICIPANTS: Deaths from CODs (3-position ICD-10 codes) with ≥5 average annual deaths in a 15-year period between 2000 and 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Fitting polynomial regression models, we examined for each COD in each country whether or not changes over time were statistically significant (with α=0.05) and we assessed correlates of this outcome. Applying receiver operating characteristicROC curve diagnostics, we derived COD size thresholds for selecting CODs for trends analysis. RESULTS: Across all countries, 64.0% of CODs had significant long-term trends. The odds of having a significant trend increased by 18% for every 10% increase of COD size. The independent effect of country was negligible. As compared to circulatory system diseases, the probability of a significant trend was lower for neoplasms and digestive system diseases, and higher for infectious diseases, mental diseases and signs-and-symptoms. We derived a general threshold of around 30 (range: 28-33) annual deaths for inclusion of a COD in trend analysis. The relevant threshold for neoplasms was around 65 (range: 61-70) and for infectious diseases was 20 (range: 19-20). CONCLUSIONS: The likelihood that long-term trends are detected with statistical significance is strongly related to COD size and varies between ICD-10 chapters, but has no independent relation to country. We recommend a general size criterion of 30 annual deaths to select CODs for long-term mortality-trends analysis in European countries.

Detecting Mortality Trends in the Netherlands Across 625 Causes of Death.

Cause of death (COD) data are essential to public health monitoring and policy. This study aims to determine the proportion of CODs, at ICD-10 three-position level, for which a long-term or short-term trend can be identified, and to examine how much the likelihood of identifying trends varies with COD size. We calculated annual age-standardized counts of deaths from Statistics Netherlands for the period 1996-2015 for 625 CODs. We applied linear regression models to estimate long-term trends, and outlier analysis to detect short-term changes. The association of the likelihood of a long-term trend with COD size was analyzed with multinomial logistic regression. No long-term trend could be demonstrated for 216 CODs (34.5%). For the remaining 409 causes, a trend could be detected, following a linear (211, 33.8%), quadratic (126, 20.2%) or cubic model (72, 11.5%). The probability of detecting a long-term trend increased from about 50% at six mean annual deaths, to 65% at 22 deaths and 75% at 60 deaths. An exceptionally high or low number of deaths in a single year was found for 16 CODs. When monitoring long-term mortality trends, one could consider a much broader range of causes of death, including ones with a relatively low number of annual deaths, than commonly used in condensed lists.

20 year trends in renal disease mortality in Ghana: A review of autopsies.

AIM: Data on the changing levels in renal morbidity and mortality are scant globally. We sought to assess trends in renal disease mortality and attributable causes over a 20 year period in Ghana. METHODS: A retrospective analysis of 20 year autopsy records of the Pathology Departments of leading teaching hospitals in Ghana, (Korle-Bu Teaching Hospital (KBTH) in Accra and Komfo Anokye Teaching Hospital (KATH) in Kumasi) from January 1994 to December 2013. Data comprising autopsies from in-patients, community cases and coroners' cases were used. We defined primary cause of death as death directly due to renal disease and secondary cause of death as death in which renal disease was a comorbid or contributing factor. RESULTS: Over the period, there were a total of 94 309 deaths, of which 5608 were attributed to renal disease (5.9/100). Mortality rate remained fairly the same from 1994 to 2009 (5.0%), but doubled from 2010 to 2013 (10.8%). Similar trends were observed among males and females during the same period. However, males had slightly higher mortality rates (6.6%; 95% CI: 46.1%-6.8%) compared to females (5.6%; 95% CI: 5.4%-5.8%; P = 0.271). The major leading attributable causes of renal disease death include end stage renal disease 45.0% and acute pyelonephritis accounting for 20.9% of the cases. Hypertensive heart disease accounted for 30.0% of all secondary cause of death while congestive heart disease and septicaemia accounted for 13.0% and 12.0%, respectively. CONCLUSIONS: We observed marked increase in the renal disease mortality rate during the last few years predominantly driven by chronic and infectious related renal diseases as a main cause, and hypertensive heart disease and congestive heart failure as the main secondary causes. Measures geared towards prevention, treatment and managing such conditions may impact on the reduction of renal disease mortality rate among Ghanaian populations.

Comparing causes of death of Hodgkin lymphoma and breast cancer patients between medical records and cause-of-death statistics.

OBJECTIVE: Obtaining accurate data about causes of death may be difficult in patients with a complicated disease history, including cancer survivors. This study compared causes of death derived from medical records (CODMR) with causes of death derived from death certificates (CODDC) as processed by Statistics Netherlands of patients primarily treated for Hodgkin lymphoma (HL) or breast cancer (BC). METHODS: Two hospital-based cohorts comprising 1,215 HL patients who died in the period 1980-2013 and 714 BC patients who died in the period 2000-2013 were linked with cause-of-death statistics files. The level of agreement was assessed for common underlying causes of death using Cohen's kappa, and original death certificates were reviewed when CODDC and CODMR showed discrepancies. We examined the influence of using CODDC or CODMR on standardized mortality ratio (SMR) estimates. RESULTS: Agreement for the most common causes of death, including selected malignant neoplasms and circulatory and respiratory diseases, was 81% for HL patients and 97% for BC patients. HL was more often reported as CODDC (CODDC=33.1% vs. CODMR=23.2%), whereas circulatory disease (CODDC=15.6% vs. CODMR=20.9%) or other diseases potentially related to HL treatment were more often reported as CODMR. Compared to SMRs based on CODDC, SMRs based on CODMR complemented with CODDC were lower for HL and higher for circulatory disease. CONCLUSION: Overall, we observed high levels of agreement between CODMR and CODDC for common causes of death in HL and BC patients. Observed discrepancies between CODMR and CODDC frequently occurred in the presence of late effects of treatment for HL.

Trend study on the association between hospital admissions and the health of Dutch older adults (1995-2009).

OBJECTIVES: An increase in hospital admission rates in older people may reflect improved access to healthcare, but also declining health trends in the older population. Owing to a lack of individual-level data, the latter possibility has received little attention. The current study examines associations between health status and hospitalisation rates of older adults in the Netherlands. DESIGN: Observational individual-level data linked to hospital register data. SETTING: Data from 1995 to 2009 from the nationally representative Longitudinal Aging Study Amsterdam were linked to the Dutch Hospital Discharge Register. PARTICIPANTS: A total of 5681 observations of 2520 respondents across 4 measurement points (each with a follow-up of 36 months; ages 65-88 years). OUTCOME MEASURES: The contribution of health, demographic, psychosocial and lifestyle characteristics to time trends in hospitalisation was assessed in multivariate models. RESULTS: Between 1995 and 2009, the percentage with 1 or more overnight admissions (planned or acute) increased slightly from 38.1% to 39.7%. This was due to an increase in acute admission only (22.2-27.0%). Increased prevalences of chronic diseases, functional limitations and polypharmacy accounted for part of the observed increase in acute admissions. In addition, a more than doubled prevalence of day admissions over time was observed (12.3-28.3%), a trend that was unrelated to changes in individual characteristics. CONCLUSIONS: This trend study showed a contribution of declines in population health to increases in acute hospital admissions. Since these declines did not provide a full explanation, healthcare reforms and increases in treatment possibilities in this period are likely to have contributed as well.

A Novel Time Series Approach to Bridge Coding Changes with a Consistent Solution Across Causes of Death.

Revisions of the International Classification of Diseases (ICD) can lead to biases in cause-specific mortality levels and trends. We propose a novel time series approach to bridge ICD coding changes which provides a consistent solution across causes of death. Using a state space model with interventions, we performed time series analysis to cause-proportional mortality for ICD9 and ICD10 in the Netherlands (1979-2010), Canada (1979-2007) and Italy (1990-2007) on chapter level. A constraint was used to keep the sum of cause-specific interventions zero. Comparability ratios (CRs) were estimated and compared to existing bridge coding CRs for Italy and Canada. A significant ICD9 to ICD10 transition occurred among 13 cause of death groups in Italy, 7 in Canada and 3 in the Netherlands. Without the constraint, all-cause mortality after the classification change would be overestimated by 0.4 % (NL), 0.03 % (Canada) and 0.2 % (Italy). The time series CRs were in the same direction as the bridge coding CRs but deviated more from 1. A smooth corrected trend over the ICD-transition resulted from applying the time series approach. Comparing the time series CRs for Italy (2003), Canada (1999) and the Netherlands (1995) revealed interesting commonalities and differences. We demonstrated the importance of adding the constraint, the validity of our methodology and its advantages above earlier methods. Applying the method to more specific causes of death and integrating medical content to a larger extent is advocated.

Impaired survival and long-term neurological problems in benign meningioma.

PURPOSE: To assess long-term functional outcome and survival among patients with meningioma World Health Organization (WHO) grade I. METHODS: Retrospective analysis of 205 patients after resection of WHO grade I intracranial meningioma from 1985 through 2003. Expected age- and sex-specific survival was calculated by applying Dutch life-table statistics to each patient for the individual duration of follow-up. Long-term functional outcome was assessed using a mailed questionnaire to the general practitioner. RESULTS: The mean duration of follow-up was 11.5 years. Survival at 5, 10, 15, and 20 years was 92%, 81%, 63%, and 53%, respectively, which is significantly lower than the expected survival (94%, 86%, 78%, and 66%, respectively). Survival was worse with higher age (P < .001). Survival among patients younger than 45 years and older than 65 years was comparable to the expected survival but significantly worse among patients aged 45-65 years. Analysis of the cause of death suggests an excess mortality associated with both brain tumor death and stroke (P = .07). Recurrence rates at 5, 10, and 15 years were 18%, 26%, and 32%, respectively. Higher Simpson grade (P < .001) and lower age (P = .02) were associated with a higher recurrence rate. In 29 patients (14%) receiving radiotherapy, the 5-year recurrence rate was 18% and the 5-year survival was only 58%. Long-term functioning (≥ 5 years after last treatment) could be assessed in 89 long-term survivors: 29 patients (33%) showed no deficits, and 60 (67%) showed at least 1 neurological symptom, of whom 24 (27%) were unable to perform normal daily activities. CONCLUSION: Long-term survival in WHO grade I meningioma is challenged in patients more than 45 years of age. Excess mortality seems to be associated with both tumor recurrence and stroke. The majority of patients have long-term neurological problems.

Mortality after hospital admission for ruptured abdominal aortic aneurysm.

BACKGROUND: The purpose of this study is to quantify age- and gender-specific mortality risks for patients hospitalized for ruptured abdominal aortic aneurysm (rAAA). METHODS: The mortality risks for 28-day, 1-year, and 5-year were derived from a retrospective nation-wide cohort study of patients who were first hospitalized for rAAA in 1997 or 2000, formed through linkage of the Hospital Discharge Register with the Dutch population register. The Hospital Discharge Register contains a record for each hospital admission, giving information about patient demographics and diagnosis. The population register contains information on patient demographics and the mortality status of all registered persons in The Netherlands. Relations between gender and mortality within specific age groups were assessed with chi-square tests. Associations between age, gender, comorbidities, and mortality were studied in multivariate analysis with Cox regression. RESULTS: A total of 1,463 patients hospitalized for rAAA were identified (86% males). Mean age was higher in women than in men (79 vs. 72 years; 95% CI of difference: 5.0-7.4). Mortality risks at 28-day, 1-year, and 5-year increased significantly with age (28-day: from 36 to 91% in men and 59 to 92% in women; 5-year: from 51 to 97% in men and 79 to 96% in women). In patients aged <80 years, mortality risks were significantly higher in women than in men. Age (HR: 1.04; 95% CI: 1.03-1.05), previous hospitalization for congestive heart failure (HR: 1.55; 95% CI: 1.06-2.26), and cerebrovascular disease (HR: 1.60; 95% CI: 1.16-2.21) were significant predictors of short- and long-term mortality. CONCLUSIONS: Mortality risks after hospitalization for rAAA clearly increase by age and are higher in women than in men in patients aged <80 years. Because of the major effect of age and gender, future studies should consider reporting absolute mortality risks stratified by age and gender, instead of simply presenting overall mortality risks.

The reliability of cause-of-death coding in The Netherlands.

Cause-of-death statistics are a major source of information for epidemiological research or policy decisions. Information on the reliability of these statistics is important for interpreting trends in time or differences between populations. Variations in coding the underlying cause of death could hinder the attribution of observed differences to determinants of health. Therefore we studied the reliability of cause-of-death statistics in The Netherlands. We performed a double coding study. Death certificates from the month of May 2005 were coded again in 2007. Each death certificate was coded manually by four coders. Reliability was measured by calculating agreement between coders (intercoder agreement) and by calculating the consistency of each individual coder in time (intracoder agreement). Our analysis covered an amount of 10,833 death certificates. The intercoder agreement of four coders on the underlying cause of death was 78%. In 2.2% of the cases coders agreed on a change of the code assigned in 2005. The (mean) intracoder agreement of four coders was 89%. Agreement was associated with the specificity of the ICD-10 code (chapter, three digits, four digits), the age of the deceased, the number of coders and the number of diseases reported on the death certificate. The reliability of cause-of-death statistics turned out to be high (>90%) for major causes of death such as cancers and acute myocardial infarction. For chronic diseases, such as diabetes and renal insufficiency, reliability was low (<70%). The reliability of cause-of-death statistics varies by ICD-10 code/chapter. A statistical office should provide coders with (additional) rules for coding diseases with a low reliability and evaluate these rules regularly. Users of cause-of-death statistics should exercise caution when interpreting causes of death with a low reliability. Studies of reliability should take into account the number of coders involved and the number of codes on a death certificate.

Mortality after elective abdominal aortic aneurysm repair.

OBJECTIVE: Purpose of this study is to provide detailed age- and gender-specific mortality risks of patients hospitalized for elective AAA repair. SUMMARY BACKGROUND DATA: Whether to perform elective abdominal aortic aneurysm (AAA) surgery is balancing the risks of natural history against the risks of surgical intervention. Literature is lacking mortality risks after elective AAA repair with stratification by both age and gender. METHODS: Mortality risks for 28 days, 1 year, and 5 years were derived from a nationwide cohort of patients hospitalized for elective AAA repair in 1997 or 2000. This cohort was formed through linkage of the Hospital Discharge Register with the Dutch Population Register. The relations between demographics, medical history and mortality were studied by Cox regression. RESULTS: A total of 3457 patients were identified; 86% males, mean age 72 +/- 8.0 years. Mortality risks after elective AAA repair increased with age: 28-day mortality ranged from 3.3% to 27.1% in men and 3.8% to 54.3% in women, 5-year mortality from 12.9% to 78.1% in men and 24.3% to 91.3% in women. Higher age, congestive heart failure, cerebrovascular disease and diabetes mellitus were independent risk factors for 5-years mortality. CONCLUSIONS: Mortality risks after elective AAA repair are strongly age-related. Age, gender, and comorbidities should be taken into account when deciding on surgery. A general threshold of 55 mm for surgery might not be justified for all patients.

Acute myocardial infarction incidence and hospital mortality: routinely collected national data versus linkage of national registers.

BACKGROUND AND OBJECTIVE: To compare levels of and trends in incidence and hospital mortality of first acute myocardial infarction (AMI) based on routinely collected hospital morbidity data and on linked registers. Cases taken from routine hospital data are a mix of patients with recurrent and first events, and double counting occurs when cases are admitted for an event several times during 1 year. By linkage of registers, recurrent events and double counts can be excluded. STUDY DESIGN AND SETTING: In 1995 and 2000, 28,733 and 25,864 admissions for AMI were registered in the Dutch national hospital discharge register. Linkage with the population register yielded 21,565 patients with a first AMI in 1995 and 20,414 in 2000. RESULTS: In 1995 and 2000, the incidence based on the hospital register was higher than based on the linked registers in men (22% and 23% higher) and women (18% and 20% higher). In both years, hospital mortality based on the hospital register and on linked registers was similar. The decline in incidence between 1995 and 2000 was comparable whether based on standard hospital register data or linked data (18% and 20% in men, 15% and 17% in women). Similarly, the decline in hospital mortality was comparable using either approach (11% and 9% in both men and women). CONCLUSION: Although the incidence based on routine hospital data overestimates the actual incidence of first AMI based on linked registers, hospital mortality and trends in incidence and hospital mortality are not changed by excluding recurrent events and double counts. Since trends in incidence and hospital mortality of AMI are often based on national routinely collected data, it is reassuring that our results indicate that findings from such studies are indeed valid and not biased because of recurrent events and double counts.

Short- and long-term prognosis after acute myocardial infarction in men versus women.

The prevailing view is that women have a higher early mortality after acute myocardial infarction (AMI) than men, but several studies have shown no differences. Further, long-term differences have not been addressed widely. The present study examined gender differences in short- and long-term prognoses after AMI in The Netherlands. A nationwide cohort of 21,565 patients with a first hospitalized AMI in 1995 was identified through linkage of the National Hospital Discharge Register and the population register. Crude short- and long-term mortalities were significantly higher in women than in men (28-day hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.58 to 1.82; 5-year HR 1.52, 95% CI 1.46 to 1.59). After adjustment for age, the risk difference was attenuated at 28 days and even reversed at 5 years in favor of women (28-day HR 1.11, 95% CI 1.03 to 1.20; 5-year HR 0.94, 95% CI 0.90 to 0.99). When differences in other covariates were also taken into account, the risk differences remained virtually the same. To account for differences in reperfusion procedures, we repeated the analyses in 1,176 patients who underwent acute reperfusion therapy (angioplasty/thrombolysis). Comparable, but not statistically significant, gender differences were observed (28-day HR 1.06, 95% CI 0.65 to 1.74; 5-year HR 0.82, 95% CI 0.62 to 1.08). In conclusion, our findings in an unselected cohort covering a complete nation indicate that the worse short- and long-term prognoses after an AMI in women compared with men may largely be explained by differences in age, whereas differences in co-morbidity, origin, infarct location, and reperfusion therapy seem to contribute little.