- Email: [email protected]
Risk factors for in-hospital mortality in patients with dementia
Maturitas 129 (2019) 57–61
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Risk factors for in-hospital mortality in patients with dementia a,b,⁎
c
d
T d
Nienke M.S. Golüke , Irene E. van de Vorst , Ilonca H. Vaartjes , Mirjam I. Geerlings , Annemarieke de Jongheb, Michiel L. Botsd, Huiberdina L. Koeka a
University Medical Center Utrecht, Department of Geriatrics, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands Tergooi Ziekenhuizen, Department of Geriatrics, Rijksstraatweg 1, 1261 AN Blaricum, the Netherlands OLVG, Department of Geriatrics, Jan Tooropstraat 164, 1061 AE Amsterdam, the Netherlands d Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands b c
A R T I C LE I N FO
A B S T R A C T
Keywords: In-hospital mortality Dementia Risk factors Older adults Prognosis
Objective: To examine the in-hospital mortality rate, and its risk factors, for patients with dementia admitted to hospital. Study design: We constructed an observational cohort study through data linkage of three Dutch national registers: the hospital discharge register (HDR), the population register (PR) and the national cause of death register. Patients with dementia in the HDR aged between 60 and 100 years registered between 1 January 2000 and 31 December 2010 were included. Main outcome measures: Risk factors for in-hospital mortality were investigated using multivariable Cox proportional hazard regression models that included sex, age, marital status, ethnicity, somatic comorbidity, type of dementia and urgency of admission. Results: 40,500 patients were included in the cohort. The overall in-hospital mortality rate was 11.1%. Factors that significantly increased the mortality risk were: male sex (adjusted hazard ratio (HR) 1.52, 95%-confidence interval (95%-CI) 1.43–1.63), higher age (adjusted HR 1.03, 95%-CI 1.03–1.04), living with a partner (adjusted HR 1.39, 95%-CI 1.30–1.49), acute admission (adjusted HR 2.16, 95%-CI 1.97–2.36) and Alzheimer’s disease (adjusted HR 1.21, 95%-CI 1.13–1.29). Cardiovascular disease was the most common cause of in-hospital mortality. Conclusions: This nationwide study found several independent risk factors for the in-hospital mortality of patients with dementia, including male sex, higher age, living with a partner, acute admission, and Alzheimer’s disease. These risk factors should be taken into account by clinicians and caregivers as they will indicate whether patients are at risk of a more unfavourable outcome during hospital admission.
1. Introduction
ulcer disease [13]. There is also one study that showed a decreased risk of in-hospital mortality in patients aged > 50 years with dementia admitted to hospital. However, this study also found a lower in-hospital mortality in patients with cancer, complete functional dependence and prior hospitalization. It is possible that referral bias influenced the results and patients with a limited prognosis were not admitted to hospital [14]. Most of these studies included a relatively small number of patients and patients were admitted for a specific disease, restricting the generalisability of these findings. Yet, for clinicians and caregivers it is important to know the absolute in-hospital mortality risk of patients with dementia and which of these patients are at most risk for in-hospital mortality. This information is important for clinicians to help support decision making in advanced care planning, especially in consideration to detain from
Dementia is a disease with a poor prognosis. A two to four times higher mortality risk in patients with dementia in comparison with older adults without dementia has been reported [1,2]. We previously showed that the one-year and five-year mortality of patients with dementia who were admitted in hospital exceeded the mortality of patients with cardiovascular disease. One-year mortality for patients with dementia was 30.5% and 38.3% for women and men, respectively [2]. Most studies that examined the in-hospital mortality of patients with dementia showed that dementia was related to an increased risk of in-hospital mortality [3–12]. There is one study that showed no difference in in-hospital mortality between patients with and without dementia who received endoscopic hemostasis for hemorrhagic peptic
⁎
Corresponding author at: Zambesidreef 137, 3564 CB Utrecht, the Netherlands. E-mail address: [email protected] (N.M.S. Golüke).
https://doi.org/10.1016/j.maturitas.2019.08.007 Received 25 March 2019; Received in revised form 11 June 2019; Accepted 14 August 2019 0378-5122/ © 2019 Elsevier B.V. All rights reserved.
Maturitas 129 (2019) 57–61
N.M.S. Golüke, et al.
retrieved, including congestive heart failure, cerebrovascular disease and peripheral vascular disease. Other cardiovascular disease could not be retrieved from the databases. Overall somatic comorbidity burden was categorised using the modified Charlson Comorbidity Index (CCI). This index ranges from 0 to 24 points and has proven to be a valid predictor of 1-year mortality after hospital admission. This score has been widely used in research as a measure of overall comorbidity [19]. Because all patients in our cohort had dementia, we excluded dementia from the CCI. For analysis purposes, overall comorbidity was divided into the following groups: 0–1, 2 or ≥3 points on the CCI. Marital status was retrieved from the PR and was categorised in patients married or living with a partner, and patients living alone. Also the ethnicity was retrieved from the PR and categorised in patients from Dutch ethnicity or other ethnicity (Western ethnicity apart from Dutch and non-Western ethnicity).
hospital admission. However, the risk factors of in-hospital mortality in patients with dementia have not been addressed widely. Therefore, our aim was to investigate the in-hospital mortality, and its risk factors, for patients with dementia admitted to hospital using a national wide registry to ensure generalisability. 2. Methods 2.1. Databases A cohort of dementia patients admitted to a hospital was constructed through data linkage of three Dutch national registers: the national hospital discharge register (HDR), the national population register (PR) and the national cause of death register. Since the 1960s, medical and administrative data for all admitted and day clinic patients visited the Dutch hospitals are recorded in HDR. No information on outpatient visits and nursing home residents is recorded in HDR. It contains information on patients’ demographics (such as date of birth and sex), primary and secondary diagnoses, and other admission and discharge data. The primary and secondary diagnoses are determined at discharge and coded using the 9th version of the International Classification of Disease codes (ICD-9 codes) [15]. It also contains underlying causesfor previous hospital admissions and thus provide information on previous hospitalisations since 1995. The PR contains information on all legally residing citizens in the Netherlands, including date of birth, sex, current address, postal code, nationality and native country. The national cause of death register contains information on date of death and primary and underlying causes of death. Death reports are coded according to the International Classification of Diseases codes, 10th version (ICD-10 codes) [16]. The overall validity of these registers has been shown to be high [17,18].
2.4. Outcome measures The outcomes of this study were absolute in-hospital mortality risks for patients with dementia and the relation between risk factors and inhospital mortality. Moreover, we also described the causes of death in these patients. These data were retrieved from the national cause of death register and coded in ICD-10 codes. 2.5. Statistical analysis Baseline characteristics were analysed by descriptive statistics. All continuous descriptive statistics were noted as mean and standard deviation or, in case of a skewed distribution, as median and range. Categorical data were noted as numbers and percentages. In-hospital mortality was noted in percentages. We also analysed the absolute mortality risk for specific groups stratifying the cohort by determinants which were expected to have an important influence on the in-hospital mortality. These determinants included urgency of admission, sex, age and type of dementia. Using Cox proportional hazard regression models, hazard ratios (HRs) and their corresponding 95% confidence intervals (95%-CIs) were calculated to identify risk factors for in-hospital mortality. Patients were censored in case of (in-hospital) death or at the end of the hospital admission. HRs were calculated unadjusted and adjusted for sex, age, marital status, ethnicity, comorbidity, type of dementia and urgency of admission. We used SPSS software, version 20.0 (SPSS Inc., Chicago, Illinois) for the analyses. A p-value < 0.05 was considered statistically significant.
2.2. Cohort identification We constructed a cohort using the HDR and selected all patients with a primary or secondary diagnosis of dementia (ICD-codes 290.0; 290.1; 290.3; 290.4; 294.1; 331.0; 331.1; 331.82) admitted to hospital aged between 60 and 100 years with their first dementia diagnosis between 1 January 2000 and 31 December 2010. Patients with a previous admission with a primary of secondary diagnosis of dementia during the period 1 January 1995 until 1 January 2000 were excluded. In case of multiple admissions since 1 January 2000, only the first admission was included. The included patients were linked with the PR using the record identification number assigned to each resident in the Netherlands with a mostly unique combination of date of birth, sex and the numeric part of the postal code. Next, we linked the national cause of death register to retrieve data on date and cause(s) of death. Patients with dementia were included from their earliest date of admission in the HDR and were censored in case of in-hospital death or at the end of the hospital admission.
2.6. Ethics Linkage of data from the different registries was performed in agreement with the privacy legislation in the Netherlands [20]. Only anonymised records and data sets were involved. The study did not have to be assessed according to the regulations of the research complying with the Dutch law on Medical Research in Humans. All linkages and analyses were performed in a secure environment of Statistics Netherlands.
2.3. Determinants We obtained the following data for the cohort: age, sex, ethnicity, marital status (married/living together, or alone), type of dementia, somatic comorbidities, cardiovascular disease, urgency of admission and cause of death. All the dementia diagnoses, somatic comorbidities and urgency of admission were retrieved, in ICD-9 codes, from the HDR. The type of dementia was categorised in vascular dementia, Alzheimer’s disease or other types of dementia. An earlier validation study performed on this cohort showed a high validity of the use of ICD-9 codes to identify dementia patients and these two subtypes. The positive predictive value for dementia was 93.2%, for Alzheimer’s dementia 63.2% and for vascular dementia 91.3% [18]. The urgency of admission was either acute of elective. Information on major cardiovascular disease was also
3. Results A total of 40,500 patients were included in our cohort. The majority was female (61.0%) and the median age was 83 years (range: 60–99 years). Most patients were of Dutch ethnicity and the majority lived alone. The most common dementia type was Alzheimer’s disease (66.8%). More than three-quarters of the admissions were acute. These and more baseline characteristics are shown in Table 1. 58
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Table 1 Baseline characteristics of patients with dementia admitted to hospital (n = 40,500). Male (n,%) Age in years (median, range) Age in years (n,%) 60-69 years 70-79 years 80-89 years 90-99 years Marital status (n,%) Married/living together Alone Ethnicity (n,%) Dutch Other Western Non-Western Charlson comorbidity index (n,%) 0-1 2 ≥3 Cardiovascular disease (n,%) Dementia (n,%) Alzheimer Vascular Other Urgency of admission Acute Elective
Table 2 Risk factors for in-hospital mortality in patients with dementia. In-hospital mortality
15783 (39.0) 83.0 (60-99) 1947 (4.8) 11178 (27.6) 22015 (54.4) 5360 (13.2)
Sex Male
13747 (33.9) 26753 (66.1) 38049 (93.9) 2451 (6.1) 1044 (2.6) 1407 (3.5) 34858 (86.1) 3853 (9.5) 1789 (4.4) 7106 (17.5) 27073 (66.8) 5142 (12.7) 8285 (20.5) 30991 (76.5) 9509 (23.5)
3.1. In-hospital mortality The in-hospital mortality for our cohort was 11.1% (for men 14.1% and women 9.2%). In case of in-hospital mortality the mean duration between admission and death was 20.9 days, standard deviation 29.0 (data not shown). The absolute mortality risks per variable are shown in Table 2. In Table 3, the absolute in-hospital mortality risk is stratified by type of dementia, urgency of admission, age and sex. There you can see that the in-hospital mortality for a 83-year old man with Alzheimer’s disease who was acutely admitted was 17.0% and for a 85-year old woman with vascular dementia who was electively admitted was 3.9%. The most common cause of death was cardiovascular disease (23.7%), followed by infectious diseases, accidents, malignancies and cerebrovascular disease (Table 4). The other causes of death consisted of a large variety of causes including metabolic disease, neurologic diseases (excluding cerebrovascular disease), urogenital diseases (excluding urogenital infections) and there were 0.4% unknown causes of death.
Absolute mortality (n,%)
Crude HR, 95%-CI
Adjusted HR1, 95%-CI
2224 (14.1)
1.58 (1.491.67)* Ref. 1.02 (1.021.03)*
1.52 (1.431.63)* Ref. 1.03 (1.031.04)*
1.43 (1.341.51)* Ref.
1.39 (1.301.49)* Ref.
1.01 (0.891.14) Ref. 0.96 (0.931.05)
0.95 (0.84-1.08)
Female Age
274 (9.2)
60-69 years 70-79 years 80-89 years 90-99 years Marital Status Married/living together
145 (7.4) 1084 (9.7) 2533 (11.5) 736 (13.7)
Alone Ethnicity Dutch
2623 (9.8)
Other CCI
270 (11.0)
0-1 2 ≥3 Cardiovascular disease Present
3890 (11.2) 405 (10.5) 203 (11.3)
No cardiovascular disease Dementia2 Alzheimer
3728 (11.2)
Vascular
541 (10.5)
Other
725 (8.8)
Urgency of admission Acute
3929 (12.7))
Elective
569 (6.0)
1875 (13.6)
4228 (11.1)
770 (10.8)
3232 (11.9))
Ref. 0.96 (0.91-1.02)
0.96 (0.891.04) Ref.
0.93 (0.86-1.00)
1.31 (1.221.39)* 0.92 (0.841.00) 0.73 (0.680.79)*
1.21 (1.131.29)* 0.96 (0.87-1.05) 0.79 (0.730.86)*
2.26 (2.072.46)* Ref.
2.16 (1.972.36)* Ref.
Ref.
HR = hazard ratio. 95%-CI = 95%-confidence interval. Ref = reference. CCI = Charlson Comorbidity Index. 1: adjusted for gender, age, marital status, ethnicity, comorbidities, type of dementia and urgency of admission. 2: HR of a specific type of dementia compared to all other types of dementia. *p-value < 0.05.
4. Discussion 3.2. Risk factors for in-hospital mortality
This study in patients with dementia showed an in-hospital mortality rate of 11.1%. Risk factors independently increasing in-hospital mortality were male sex, higher age, living with a partner, Alzheimer’s disease and acute admission. The most common cause of in-hospital death was cardiovascular disease. The overall in-hospital mortality risk of 11.1% is comparable with results from earlier studies [6,8]. A Spanish study reported a higher inhospital mortality for patients admitted with dementia, with an inhospital mortality of 19% [10]. An earlier cohort study done in the Netherlands also showed that cardiovascular disease was the most common cause of death during a median follow up time of 1.3 years in patients with dementia admitted to hospital or who visited the day clinic [21]. An unexpected finding was that patients who were married or living together were at increased risk of mortality. Since the present study is based on registry data, an in depth analyses of the underlying mechanism of the relation between ‘living with a partner and increased
Table 2 shows the independent risk factors for in-hospital mortality and their HR. Mortality was significantly higher in male patients (adjusted HR 1.52, 95%-CI 1.43–1.63), in patients of higher age (adjusted HR 1.03, 95%-CI 1.03–1.04), in patients living with a partner compared to living alone (adjusted HR 1.39, 95%-CI 1.30–1.49) and in patients acutely admitted compared to electively admitted (adjusted HR 2.16, 95%-CI 1.97–2.36). Type of dementia also was an independent risk factor, as it was found that Alzheimer’s disease was associated with a higher mortality risk compared to vascular dementia and other types of dementia combined (adjusted HR 1.21, 95%-CI 1.13–1.29). Other types of dementia were associated with a lower mortality risk compared to Alzheimer’s and vascular dementia combined (adjusted HR 0.79, 95%-CI 0.730.86).
59
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nonrestrictive design of our cohort (all wards and all types of dementia), the results are representative for the overall (Dutch) population admitted to hospital with dementia. Our results should raise awareness in clinicians and caregivers about the unfavourable prognosis of patients with dementia, especially when they are older, men, having Alzheimer’s disease or being acutely admitted. Moreover, it is shown that cardiovascular diseases are the most common cause of in-hospital mortality. This knowledge of absolute risks, risk factors and causes of in-hospital mortality can be used in advanced care planning discussions. It is recommended to perform further studies that provide an individualized risk assessment on the prognosis of a specific patient.
Table 3 Absolute in-hospital mortality risk according to type of dementia and stratified by urgency of admission, sex, age and type of dementia.
5. Conclusion This nationwide study found an in-hospital mortality of 11.1% and several independent risk factors for in-hospital mortality of patients with dementia, including male sex, higher age, living with a partner, acute admission, and Alzheimer’s disease. Cardiovascular disease was the most common cause of in-hospital mortality. Knowledge of these risk factors can be useful for advanced care planning discussions between clinicians and caregivers of patients at risk for a more unfavourable prognosis during admission in hospital.
Green boxes comprise risks < 10%, yellow boxes risks of 11–15%, and red boxes risks of > 15%. *= not enough data. Table 4 Causes of death of patients with dementia who died during hospital admission.
Contributors Nienke MS Golüke contributed to study conception and design, data acquisition, the analysis and writing of the manuscript. Irene E van de Vorst contributed to study conception and design, data acquisition, the analysis and writing of the manuscript. Ilonca H Vaartjes contributed to study conception and design, and data acquisition. Mirjam I Geerlings contributed to study conception and design. Annemarieke de Jonghe contributed to study conception and design. Michiel L Bots contributed to study conception and design. Huiberdina L Koek contributed to study conception and design, data acquisition, the analysis and writing of the manuscript. All authors critically reviewed the draft manuscript and approved the final version.
Cause of death (n,%) Cardiovascular disease Infectious disease Pneumonia Accidents Malignancies Cerebrovascular disease Dementia Gastro-intestinal disease Chronic respiratory disease Other1 Unknown
1068 (23.7) 715 (15.9) 447 (9.9) 458 (10.2) 389 (8.6) 362 (8.0) 338 (7.5) 337 (7.5) 283 (6.3) 531 (11.9) 17 (0.4)
1 = including among others: other metabolic disease, other neurological disease, other urogenital disease.
mortality’ was not possible with our data. Yet, one may hypothesize that this relation can be explained by the fact that those with partner probably are admitted in a later (i.e, more severe state) of dementia and potentially with more (severe) co-morbidity as compared to individuals living alone. This is based on the notion that in the Netherlands people prefer to stay in their home as long as possible, with and without additional medical help. Information on severity of dementia, however, was not available from the databases. In the relevant literature marital status was not considered a possible risk factor and this was not taking into analysis. Therefore we could not compare this unexpected finding with the existing literature. Moreover, because this cohort was based on existing health care databases, the completeness and reliability of the data depend on the documentation of the health care provider. Probably, this also explains that a relatively small part of our cohort had somatic comorbidities according to the CCI (13.9% had > 1 comorbidity in the CCI). The overall validity of the registers used has been proven to be high [18]. A further limitation is that there was no comparison with a group of older adults admitted without dementia. There have been several studies done in the past stating an increased in-hospital mortality for patients with dementia compared to older adults without dementia [3–12]. Therefore it seems reasonable that older adults without dementia in our setting would have a lower in-hospital mortality risk. A strength of this study is the large, nationwide study population and the large number of risk factors being studied. Because of the
Funding This study was supported by Alzheimer Nederland (project no WE.03-2012-38) and by a grant from the Netherlands Heart Foundation (grant number 31653251) as part of the project ‘Cardiovascular disease in the Netherlands: figures and facts’ of the Netherlands Heart Foundation. The sponsors had no role in the design, conduct, writing or interpretation of the results. Ethical approval This was an observational database study and not an experimental study. Linkage of data from the different registries was performed in agreement with privacy legislation in the Netherlands. Only anonymised records and data sets were involved. All linkages and analyses were performed in the secure environment of Statistics Netherlands. Provenance and peer review This article has undergone peer review. Research data (data sharing and collaboration) There are no linked research data sets for this paper. The authors do not have permission to share the data. 60
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Declaration of Competing Interest [11]
The authors declare that they have no conflict of interest. References
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Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Risk factors for in-hospital mortality in patients with dementia a,b,⁎
c
d
T d
Nienke M.S. Golüke , Irene E. van de Vorst , Ilonca H. Vaartjes , Mirjam I. Geerlings , Annemarieke de Jongheb, Michiel L. Botsd, Huiberdina L. Koeka a
University Medical Center Utrecht, Department of Geriatrics, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands Tergooi Ziekenhuizen, Department of Geriatrics, Rijksstraatweg 1, 1261 AN Blaricum, the Netherlands OLVG, Department of Geriatrics, Jan Tooropstraat 164, 1061 AE Amsterdam, the Netherlands d Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands b c
A R T I C LE I N FO
A B S T R A C T
Keywords: In-hospital mortality Dementia Risk factors Older adults Prognosis
Objective: To examine the in-hospital mortality rate, and its risk factors, for patients with dementia admitted to hospital. Study design: We constructed an observational cohort study through data linkage of three Dutch national registers: the hospital discharge register (HDR), the population register (PR) and the national cause of death register. Patients with dementia in the HDR aged between 60 and 100 years registered between 1 January 2000 and 31 December 2010 were included. Main outcome measures: Risk factors for in-hospital mortality were investigated using multivariable Cox proportional hazard regression models that included sex, age, marital status, ethnicity, somatic comorbidity, type of dementia and urgency of admission. Results: 40,500 patients were included in the cohort. The overall in-hospital mortality rate was 11.1%. Factors that significantly increased the mortality risk were: male sex (adjusted hazard ratio (HR) 1.52, 95%-confidence interval (95%-CI) 1.43–1.63), higher age (adjusted HR 1.03, 95%-CI 1.03–1.04), living with a partner (adjusted HR 1.39, 95%-CI 1.30–1.49), acute admission (adjusted HR 2.16, 95%-CI 1.97–2.36) and Alzheimer’s disease (adjusted HR 1.21, 95%-CI 1.13–1.29). Cardiovascular disease was the most common cause of in-hospital mortality. Conclusions: This nationwide study found several independent risk factors for the in-hospital mortality of patients with dementia, including male sex, higher age, living with a partner, acute admission, and Alzheimer’s disease. These risk factors should be taken into account by clinicians and caregivers as they will indicate whether patients are at risk of a more unfavourable outcome during hospital admission.
1. Introduction
ulcer disease [13]. There is also one study that showed a decreased risk of in-hospital mortality in patients aged > 50 years with dementia admitted to hospital. However, this study also found a lower in-hospital mortality in patients with cancer, complete functional dependence and prior hospitalization. It is possible that referral bias influenced the results and patients with a limited prognosis were not admitted to hospital [14]. Most of these studies included a relatively small number of patients and patients were admitted for a specific disease, restricting the generalisability of these findings. Yet, for clinicians and caregivers it is important to know the absolute in-hospital mortality risk of patients with dementia and which of these patients are at most risk for in-hospital mortality. This information is important for clinicians to help support decision making in advanced care planning, especially in consideration to detain from
Dementia is a disease with a poor prognosis. A two to four times higher mortality risk in patients with dementia in comparison with older adults without dementia has been reported [1,2]. We previously showed that the one-year and five-year mortality of patients with dementia who were admitted in hospital exceeded the mortality of patients with cardiovascular disease. One-year mortality for patients with dementia was 30.5% and 38.3% for women and men, respectively [2]. Most studies that examined the in-hospital mortality of patients with dementia showed that dementia was related to an increased risk of in-hospital mortality [3–12]. There is one study that showed no difference in in-hospital mortality between patients with and without dementia who received endoscopic hemostasis for hemorrhagic peptic
⁎
Corresponding author at: Zambesidreef 137, 3564 CB Utrecht, the Netherlands. E-mail address: [email protected] (N.M.S. Golüke).
https://doi.org/10.1016/j.maturitas.2019.08.007 Received 25 March 2019; Received in revised form 11 June 2019; Accepted 14 August 2019 0378-5122/ © 2019 Elsevier B.V. All rights reserved.
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retrieved, including congestive heart failure, cerebrovascular disease and peripheral vascular disease. Other cardiovascular disease could not be retrieved from the databases. Overall somatic comorbidity burden was categorised using the modified Charlson Comorbidity Index (CCI). This index ranges from 0 to 24 points and has proven to be a valid predictor of 1-year mortality after hospital admission. This score has been widely used in research as a measure of overall comorbidity [19]. Because all patients in our cohort had dementia, we excluded dementia from the CCI. For analysis purposes, overall comorbidity was divided into the following groups: 0–1, 2 or ≥3 points on the CCI. Marital status was retrieved from the PR and was categorised in patients married or living with a partner, and patients living alone. Also the ethnicity was retrieved from the PR and categorised in patients from Dutch ethnicity or other ethnicity (Western ethnicity apart from Dutch and non-Western ethnicity).
hospital admission. However, the risk factors of in-hospital mortality in patients with dementia have not been addressed widely. Therefore, our aim was to investigate the in-hospital mortality, and its risk factors, for patients with dementia admitted to hospital using a national wide registry to ensure generalisability. 2. Methods 2.1. Databases A cohort of dementia patients admitted to a hospital was constructed through data linkage of three Dutch national registers: the national hospital discharge register (HDR), the national population register (PR) and the national cause of death register. Since the 1960s, medical and administrative data for all admitted and day clinic patients visited the Dutch hospitals are recorded in HDR. No information on outpatient visits and nursing home residents is recorded in HDR. It contains information on patients’ demographics (such as date of birth and sex), primary and secondary diagnoses, and other admission and discharge data. The primary and secondary diagnoses are determined at discharge and coded using the 9th version of the International Classification of Disease codes (ICD-9 codes) [15]. It also contains underlying causesfor previous hospital admissions and thus provide information on previous hospitalisations since 1995. The PR contains information on all legally residing citizens in the Netherlands, including date of birth, sex, current address, postal code, nationality and native country. The national cause of death register contains information on date of death and primary and underlying causes of death. Death reports are coded according to the International Classification of Diseases codes, 10th version (ICD-10 codes) [16]. The overall validity of these registers has been shown to be high [17,18].
2.4. Outcome measures The outcomes of this study were absolute in-hospital mortality risks for patients with dementia and the relation between risk factors and inhospital mortality. Moreover, we also described the causes of death in these patients. These data were retrieved from the national cause of death register and coded in ICD-10 codes. 2.5. Statistical analysis Baseline characteristics were analysed by descriptive statistics. All continuous descriptive statistics were noted as mean and standard deviation or, in case of a skewed distribution, as median and range. Categorical data were noted as numbers and percentages. In-hospital mortality was noted in percentages. We also analysed the absolute mortality risk for specific groups stratifying the cohort by determinants which were expected to have an important influence on the in-hospital mortality. These determinants included urgency of admission, sex, age and type of dementia. Using Cox proportional hazard regression models, hazard ratios (HRs) and their corresponding 95% confidence intervals (95%-CIs) were calculated to identify risk factors for in-hospital mortality. Patients were censored in case of (in-hospital) death or at the end of the hospital admission. HRs were calculated unadjusted and adjusted for sex, age, marital status, ethnicity, comorbidity, type of dementia and urgency of admission. We used SPSS software, version 20.0 (SPSS Inc., Chicago, Illinois) for the analyses. A p-value < 0.05 was considered statistically significant.
2.2. Cohort identification We constructed a cohort using the HDR and selected all patients with a primary or secondary diagnosis of dementia (ICD-codes 290.0; 290.1; 290.3; 290.4; 294.1; 331.0; 331.1; 331.82) admitted to hospital aged between 60 and 100 years with their first dementia diagnosis between 1 January 2000 and 31 December 2010. Patients with a previous admission with a primary of secondary diagnosis of dementia during the period 1 January 1995 until 1 January 2000 were excluded. In case of multiple admissions since 1 January 2000, only the first admission was included. The included patients were linked with the PR using the record identification number assigned to each resident in the Netherlands with a mostly unique combination of date of birth, sex and the numeric part of the postal code. Next, we linked the national cause of death register to retrieve data on date and cause(s) of death. Patients with dementia were included from their earliest date of admission in the HDR and were censored in case of in-hospital death or at the end of the hospital admission.
2.6. Ethics Linkage of data from the different registries was performed in agreement with the privacy legislation in the Netherlands [20]. Only anonymised records and data sets were involved. The study did not have to be assessed according to the regulations of the research complying with the Dutch law on Medical Research in Humans. All linkages and analyses were performed in a secure environment of Statistics Netherlands.
2.3. Determinants We obtained the following data for the cohort: age, sex, ethnicity, marital status (married/living together, or alone), type of dementia, somatic comorbidities, cardiovascular disease, urgency of admission and cause of death. All the dementia diagnoses, somatic comorbidities and urgency of admission were retrieved, in ICD-9 codes, from the HDR. The type of dementia was categorised in vascular dementia, Alzheimer’s disease or other types of dementia. An earlier validation study performed on this cohort showed a high validity of the use of ICD-9 codes to identify dementia patients and these two subtypes. The positive predictive value for dementia was 93.2%, for Alzheimer’s dementia 63.2% and for vascular dementia 91.3% [18]. The urgency of admission was either acute of elective. Information on major cardiovascular disease was also
3. Results A total of 40,500 patients were included in our cohort. The majority was female (61.0%) and the median age was 83 years (range: 60–99 years). Most patients were of Dutch ethnicity and the majority lived alone. The most common dementia type was Alzheimer’s disease (66.8%). More than three-quarters of the admissions were acute. These and more baseline characteristics are shown in Table 1. 58
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Table 1 Baseline characteristics of patients with dementia admitted to hospital (n = 40,500). Male (n,%) Age in years (median, range) Age in years (n,%) 60-69 years 70-79 years 80-89 years 90-99 years Marital status (n,%) Married/living together Alone Ethnicity (n,%) Dutch Other Western Non-Western Charlson comorbidity index (n,%) 0-1 2 ≥3 Cardiovascular disease (n,%) Dementia (n,%) Alzheimer Vascular Other Urgency of admission Acute Elective
Table 2 Risk factors for in-hospital mortality in patients with dementia. In-hospital mortality
15783 (39.0) 83.0 (60-99) 1947 (4.8) 11178 (27.6) 22015 (54.4) 5360 (13.2)
Sex Male
13747 (33.9) 26753 (66.1) 38049 (93.9) 2451 (6.1) 1044 (2.6) 1407 (3.5) 34858 (86.1) 3853 (9.5) 1789 (4.4) 7106 (17.5) 27073 (66.8) 5142 (12.7) 8285 (20.5) 30991 (76.5) 9509 (23.5)
3.1. In-hospital mortality The in-hospital mortality for our cohort was 11.1% (for men 14.1% and women 9.2%). In case of in-hospital mortality the mean duration between admission and death was 20.9 days, standard deviation 29.0 (data not shown). The absolute mortality risks per variable are shown in Table 2. In Table 3, the absolute in-hospital mortality risk is stratified by type of dementia, urgency of admission, age and sex. There you can see that the in-hospital mortality for a 83-year old man with Alzheimer’s disease who was acutely admitted was 17.0% and for a 85-year old woman with vascular dementia who was electively admitted was 3.9%. The most common cause of death was cardiovascular disease (23.7%), followed by infectious diseases, accidents, malignancies and cerebrovascular disease (Table 4). The other causes of death consisted of a large variety of causes including metabolic disease, neurologic diseases (excluding cerebrovascular disease), urogenital diseases (excluding urogenital infections) and there were 0.4% unknown causes of death.
Absolute mortality (n,%)
Crude HR, 95%-CI
Adjusted HR1, 95%-CI
2224 (14.1)
1.58 (1.491.67)* Ref. 1.02 (1.021.03)*
1.52 (1.431.63)* Ref. 1.03 (1.031.04)*
1.43 (1.341.51)* Ref.
1.39 (1.301.49)* Ref.
1.01 (0.891.14) Ref. 0.96 (0.931.05)
0.95 (0.84-1.08)
Female Age
274 (9.2)
60-69 years 70-79 years 80-89 years 90-99 years Marital Status Married/living together
145 (7.4) 1084 (9.7) 2533 (11.5) 736 (13.7)
Alone Ethnicity Dutch
2623 (9.8)
Other CCI
270 (11.0)
0-1 2 ≥3 Cardiovascular disease Present
3890 (11.2) 405 (10.5) 203 (11.3)
No cardiovascular disease Dementia2 Alzheimer
3728 (11.2)
Vascular
541 (10.5)
Other
725 (8.8)
Urgency of admission Acute
3929 (12.7))
Elective
569 (6.0)
1875 (13.6)
4228 (11.1)
770 (10.8)
3232 (11.9))
Ref. 0.96 (0.91-1.02)
0.96 (0.891.04) Ref.
0.93 (0.86-1.00)
1.31 (1.221.39)* 0.92 (0.841.00) 0.73 (0.680.79)*
1.21 (1.131.29)* 0.96 (0.87-1.05) 0.79 (0.730.86)*
2.26 (2.072.46)* Ref.
2.16 (1.972.36)* Ref.
Ref.
HR = hazard ratio. 95%-CI = 95%-confidence interval. Ref = reference. CCI = Charlson Comorbidity Index. 1: adjusted for gender, age, marital status, ethnicity, comorbidities, type of dementia and urgency of admission. 2: HR of a specific type of dementia compared to all other types of dementia. *p-value < 0.05.
4. Discussion 3.2. Risk factors for in-hospital mortality
This study in patients with dementia showed an in-hospital mortality rate of 11.1%. Risk factors independently increasing in-hospital mortality were male sex, higher age, living with a partner, Alzheimer’s disease and acute admission. The most common cause of in-hospital death was cardiovascular disease. The overall in-hospital mortality risk of 11.1% is comparable with results from earlier studies [6,8]. A Spanish study reported a higher inhospital mortality for patients admitted with dementia, with an inhospital mortality of 19% [10]. An earlier cohort study done in the Netherlands also showed that cardiovascular disease was the most common cause of death during a median follow up time of 1.3 years in patients with dementia admitted to hospital or who visited the day clinic [21]. An unexpected finding was that patients who were married or living together were at increased risk of mortality. Since the present study is based on registry data, an in depth analyses of the underlying mechanism of the relation between ‘living with a partner and increased
Table 2 shows the independent risk factors for in-hospital mortality and their HR. Mortality was significantly higher in male patients (adjusted HR 1.52, 95%-CI 1.43–1.63), in patients of higher age (adjusted HR 1.03, 95%-CI 1.03–1.04), in patients living with a partner compared to living alone (adjusted HR 1.39, 95%-CI 1.30–1.49) and in patients acutely admitted compared to electively admitted (adjusted HR 2.16, 95%-CI 1.97–2.36). Type of dementia also was an independent risk factor, as it was found that Alzheimer’s disease was associated with a higher mortality risk compared to vascular dementia and other types of dementia combined (adjusted HR 1.21, 95%-CI 1.13–1.29). Other types of dementia were associated with a lower mortality risk compared to Alzheimer’s and vascular dementia combined (adjusted HR 0.79, 95%-CI 0.730.86).
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nonrestrictive design of our cohort (all wards and all types of dementia), the results are representative for the overall (Dutch) population admitted to hospital with dementia. Our results should raise awareness in clinicians and caregivers about the unfavourable prognosis of patients with dementia, especially when they are older, men, having Alzheimer’s disease or being acutely admitted. Moreover, it is shown that cardiovascular diseases are the most common cause of in-hospital mortality. This knowledge of absolute risks, risk factors and causes of in-hospital mortality can be used in advanced care planning discussions. It is recommended to perform further studies that provide an individualized risk assessment on the prognosis of a specific patient.
Table 3 Absolute in-hospital mortality risk according to type of dementia and stratified by urgency of admission, sex, age and type of dementia.
5. Conclusion This nationwide study found an in-hospital mortality of 11.1% and several independent risk factors for in-hospital mortality of patients with dementia, including male sex, higher age, living with a partner, acute admission, and Alzheimer’s disease. Cardiovascular disease was the most common cause of in-hospital mortality. Knowledge of these risk factors can be useful for advanced care planning discussions between clinicians and caregivers of patients at risk for a more unfavourable prognosis during admission in hospital.
Green boxes comprise risks < 10%, yellow boxes risks of 11–15%, and red boxes risks of > 15%. *= not enough data. Table 4 Causes of death of patients with dementia who died during hospital admission.
Contributors Nienke MS Golüke contributed to study conception and design, data acquisition, the analysis and writing of the manuscript. Irene E van de Vorst contributed to study conception and design, data acquisition, the analysis and writing of the manuscript. Ilonca H Vaartjes contributed to study conception and design, and data acquisition. Mirjam I Geerlings contributed to study conception and design. Annemarieke de Jonghe contributed to study conception and design. Michiel L Bots contributed to study conception and design. Huiberdina L Koek contributed to study conception and design, data acquisition, the analysis and writing of the manuscript. All authors critically reviewed the draft manuscript and approved the final version.
Cause of death (n,%) Cardiovascular disease Infectious disease Pneumonia Accidents Malignancies Cerebrovascular disease Dementia Gastro-intestinal disease Chronic respiratory disease Other1 Unknown
1068 (23.7) 715 (15.9) 447 (9.9) 458 (10.2) 389 (8.6) 362 (8.0) 338 (7.5) 337 (7.5) 283 (6.3) 531 (11.9) 17 (0.4)
1 = including among others: other metabolic disease, other neurological disease, other urogenital disease.
mortality’ was not possible with our data. Yet, one may hypothesize that this relation can be explained by the fact that those with partner probably are admitted in a later (i.e, more severe state) of dementia and potentially with more (severe) co-morbidity as compared to individuals living alone. This is based on the notion that in the Netherlands people prefer to stay in their home as long as possible, with and without additional medical help. Information on severity of dementia, however, was not available from the databases. In the relevant literature marital status was not considered a possible risk factor and this was not taking into analysis. Therefore we could not compare this unexpected finding with the existing literature. Moreover, because this cohort was based on existing health care databases, the completeness and reliability of the data depend on the documentation of the health care provider. Probably, this also explains that a relatively small part of our cohort had somatic comorbidities according to the CCI (13.9% had > 1 comorbidity in the CCI). The overall validity of the registers used has been proven to be high [18]. A further limitation is that there was no comparison with a group of older adults admitted without dementia. There have been several studies done in the past stating an increased in-hospital mortality for patients with dementia compared to older adults without dementia [3–12]. Therefore it seems reasonable that older adults without dementia in our setting would have a lower in-hospital mortality risk. A strength of this study is the large, nationwide study population and the large number of risk factors being studied. Because of the
Funding This study was supported by Alzheimer Nederland (project no WE.03-2012-38) and by a grant from the Netherlands Heart Foundation (grant number 31653251) as part of the project ‘Cardiovascular disease in the Netherlands: figures and facts’ of the Netherlands Heart Foundation. The sponsors had no role in the design, conduct, writing or interpretation of the results. Ethical approval This was an observational database study and not an experimental study. Linkage of data from the different registries was performed in agreement with privacy legislation in the Netherlands. Only anonymised records and data sets were involved. All linkages and analyses were performed in the secure environment of Statistics Netherlands. Provenance and peer review This article has undergone peer review. Research data (data sharing and collaboration) There are no linked research data sets for this paper. The authors do not have permission to share the data. 60
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Declaration of Competing Interest [11]
The authors declare that they have no conflict of interest. References
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