Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician.

INTRODUCTION: Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. METHODS: A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. DISCUSSION: The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. TRIAL REGISTRATION: German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.

Associations between care home residents' characteristics and acute hospital admissions - a retrospective, register-based cross-sectional study.

BACKGROUND: Care home residents are frail, multi-morbid, and have an increased risk of experiencing acute hospitalisations and adverse events. This study contributes to the discussion on preventing acute admissions from care homes. We aim to describe the residents' health characteristics, survival after care home admission, contacts with the secondary health care system, patterns of admissions, and factors associated with acute hospital admissions. METHOD: Data on all care home residents aged 65 + years living in Southern Jutland in 2018-2019 (n = 2601) was enriched with data from highly valid Danish national health registries to obtain information on characteristics and hospitalisations. Characteristics of care home residents were assessed by sex and age group. Factors associated with acute admissions were analysed using Cox Regression. RESULTS: Most care home residents were women (65.6%). Male residents were younger at the time of care home admission (mean 80.6 vs. 83.7 years), had a higher prevalence of morbidities, and shorter survival after care home admission. The 1-year survival was 60.8% and 72.3% for males and females, respectively. Median survival was 17.9 months and 25.9 months for males and females, respectively. The mean rate of acute hospitalisations was 0.56 per resident-year. One in four (24.4%) care home residents were discharged from the hospital within 24 h. The same proportion was readmitted within 30 days of discharge (24.6%). Admission-related mortality was 10.9% in-hospital and 13.0% 30 days post-discharge. Male sex was associated with acute hospital admissions, as was a medical history of various cardiovascular diseases, cancer, chronic obstructive pulmonary disease, and osteoporosis. In contrast, a medical history of dementia was associated with fewer acute admissions. CONCLUSION: This study highlights some of the major characteristics of care home residents and their acute hospitalisations and contributes to the ongoing discussion on improving or preventing acute admissions from care homes. TRIAL REGISTRATION: Not relevant.

Long-Lived Individuals Show a Lower Burden of Variants Predisposing to Age-Related Diseases and a Higher Polygenic Longevity Score.

Longevity is a complex phenotype influenced by both environmental and genetic factors. The genetic contribution is estimated at about 25%. Despite extensive research efforts, only a few longevity genes have been validated across populations. Long-lived individuals (LLI) reach extreme ages with a relative low prevalence of chronic disability and major age-related diseases (ARDs). We tested whether the protection from ARDs in LLI can partly be attributed to genetic factors by calculating polygenic risk scores (PRSs) for seven common late-life diseases (Alzheimer's disease (AD), atrial fibrillation (AF), coronary artery disease (CAD), colorectal cancer (CRC), ischemic stroke (ISS), Parkinson's disease (PD) and type 2 diabetes (T2D)). The examined sample comprised 1351 German LLI (≥94 years, including 643 centenarians) and 4680 German younger controls. For all ARD-PRSs tested, the LLI had significantly lower scores than the younger control individuals (areas under the curve (AUCs): ISS = 0.59, p = 2.84 × 10-35; AD = 0.59, p = 3.16 × 10-25; AF = 0.57, p = 1.07 × 10-16; CAD = 0.56, p = 1.88 × 10-12; CRC = 0.52, p = 5.85 × 10-3; PD = 0.52, p = 1.91 × 10-3; T2D = 0.51, p = 2.61 × 10-3). We combined the individual ARD-PRSs into a meta-PRS (AUC = 0.64, p = 6.45 × 10-15). We also generated two genome-wide polygenic scores for longevity, one with and one without the TOMM40/APOE/APOC1 gene region (AUC (incl. TOMM40/APOE/APOC1) = 0.56, p = 1.45 × 10-5, seven variants; AUC (excl. TOMM40/APOE/APOC1) = 0.55, p = 9.85 × 10-3, 10,361 variants). Furthermore, the inclusion of nine markers from the excluded region (not in LD with each other) plus the APOE haplotype into the model raised the AUC from 0.55 to 0.61. Thus, our results highlight the importance of TOMM40/APOE/APOC1 as a longevity hub.

Older patients acutely admitted and readmitted to the same geriatric department: a descriptive cohort study of primary diagnoses and health characteristics.

PURPOSE: Advancing age is associated with increased risk for acute admissions and readmissions. The societal challenges of ageing populations have made the prevention of readmissions come into focus. Readmission may be perceived as the result of inadequate treatment during index admission but may also be caused by the onset of new disease following a generally impaired health of geriatric patients. We aimed at comparing the diagnoses at index and readmission to illuminate this issue. METHODS: This is a descriptive, retrospective cohort study of patients acutely admitted and readmitted (within 30 days from discharge) to the same geriatric ward (November 1, 2017-April 30, 2018). Electronic medical records were scrutinised manually for discharge diagnoses and patient characteristics. RESULTS: Readmission rate was 10.7% (98 of 918 unique admissions). Mean age was 85.6 (men 56%). About 75% were readmitted with a new acute disease unrelated to index admission, most commonly pneumonia (27%), other infections (22%), and dehydration (14%). The health characteristics were long index length-of-stay (median 7; IQR 5-11), high Charlson Comorbidity Index (CCI ≥ 3, n = 49 (50%), polypharmacy (≥ 5 prescriptions) (94%), and hospitalisations 12 months prior to index admission (57%). KEY CONCLUSIONS: The majority of readmitted geriatric patients have contracted a new acute condition. Although being characterised by several adverse health characteristics, prospective studies comparing readmitted and non-readmitted geriatric patients are needed. Still, increasing the awareness of early recognition of acute disease onset in geriatric patients is warranted.

Protocol for EXICODE: the EXIstential health COhort DEnmark-a register and survey study of adult Danes.

INTRODUCTION: We established the EXIstential health COhort DEnmark (EXICODE) to examine how existential and spiritual needs, practices and orientations in a secular culture are linked to health outcomes, illness trajectory and overall cost of care in patients. Substantial literature demonstrates that existential and spiritual well-being has positive effects on health. While people turn to existential and spiritual orientations and practices during ageing, struggle with illness and approaching death, patients with severe illnesses like, for example, cancer similarly experience existential and spiritual needs. These needs are often unmet in secular societies leading to spiritual pain, unnecessary suffering, worse quality of life and higher medical costs of care. METHODS AND ANALYSIS: EXICODE is a national cohort comprising a 10% random sample of the adult Danish population with individual-level register and survey data. Specific patient subgroups are oversampled to ensure diseased respondents. The questionnaire used in the survey consists of a collection of validated instruments on existential and spiritual constructs suited for secular culture as well as some ad hoc questions compiled in the comprehensive EXICODE Questionnaire. ETHICS AND DISSEMINATION: The project is registered for legal and GDPR concerns by the University of Southern Denmark, journal number: 10.367. Ethical approval was not required by Danish law since EXICODE collects only interview, survey and register data, but due to institutional best-practice policy an ethical evaluation and approval were nevertheless obtained from the University of Southern Denmark Research Ethics Committee (institutional review board), journal number: 20/39546. The project follows The Danish Code of Conduct for Research Integrity and is carried out in accordance with the Helsinki Declaration. Results will be disseminated widely through publications in peer-reviewed scientific journals, international conferences, patient societies as well as mass and social media.

Association of Body Mass Index With All-Cause Mortality in Acutely Hospitalized Older Patients.

OBJECTIVES: The aim was to examine the relationship between body mass index (BMI) and mortality in older hospitalized patients taking activities of daily living (ADLs) into account. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Nationwide population-based study of all patients aged ≥65 years admitted to Danish geriatric medical departments during 2005 to 2014 and included in the National Danish Geriatric Database. METHODS: Patients were followed until death, emigration, or study termination (December 31, 2015). Primary outcome was all-cause mortality. BMI and ADLs were routinely assessed on admission and linked at an individual level to the Danish national health registers. Kaplan-Meier analysis was used to estimate crude survival according to each BMI subcategory and Cox regression to examine the association with mortality adjusting for age, comorbidity, polypharmacy, ADLs, marital status, prior hospitalizations, and admission year. RESULTS: In total, 74,589 patients (63% women) were included aged [mean (SD)] 82.5 (7.5) years with BMI [mean (SD)] of 23.9 (5.1) kg/m2. During follow-up 51,188 died. Follow-up time was 191,972 person-years. Unadjusted and adjusted hazard ratio (HR) for overall, 30-day, and 1-year mortality decreased significantly with increasing BMI. In women, the highest adjusted HR (95% confidence interval) for overall mortality was seen for underweight patients (BMI <16) 1.83 (1.72-1.95) and the lowest for obesity grade II patients (BMI = 35.0-39.9) 0.66 (0.60-0.73) when using normal weight (BMI = 18.5-24.9) as reference. In men, the HR for BMI <16 and BMI = 35.0-39.9 were 1.98 (1.76-2.23) and 0.56 (0.49-0.65), respectively. CONCLUSIONS AND IMPLICATIONS: In hospitalized older patients, association between mortality and BMI did not show a U-shaped or J-shaped curve after adjustment of multiple confounders, including ADLs. Instead, mortality was highest in patients with low BMI and decreased with increasing BMI before leveling off in the obese range. Our study highlights the need for a debate and reassessment of what should be the ideal BMI in this vulnerable patient group.

Skewness of X-chromosome inactivation increases with age and varies across birth cohorts in elderly Danish women.

Mosaicism in blood varies with age, and cross-sectional studies indicate that for women, skewness of X-chromosomal mosaicism increases with age. This pattern could, however, also be due to less X-inactivation in more recent birth cohorts. Skewed X-chromosome inactivation was here measured longitudinally by the HUMARA assay in 67 septuagenarian and octogenarian women assessed at 2 time points, 10 years apart, and in 10 centenarian women assessed at 2 time points, 2-7 years apart. Skewed X-chromosome inactivation was also compared in 293 age-matched septuagenarian twins born in 1917-1923 and 1931-1937, and 212 centenarians born in 1895, 1905 and 1915. The longitudinal study of septuagenarians and octogenarians revealed that 16% (95% CI 7-29%) of the women developed skewed X-inactivation over a 10-year period. In the cross-sectional across-birth cohort study, the earlier-born septuagenarian (1917-1923) and centenarian women (1895) had a higher degree of skewness than the respective recent age-matched birth cohorts, which indicates that the women in the more recent cohorts, after the age of 70, had not only changed degree of skewness with age, they had also undergone less age-related hematopoietic sub-clone expansion. This may be a result of improved living conditions and better medical treatment in the more recent birth cohorts.

Activities of daily living at hospital admission associated with mortality in geriatric patients with dementia: a Danish nationwide population-based cohort study.

PURPOSE: Determining life expectancy in patients with dementia are challenging. We aimed at studying the association between basic activities of daily living as measured by the Barthel Index at hospital admission and mortality among older patients with dementia. METHODS: All patients aged ≥ 65 years with diagnosed dementia in the population-based National Danish Geriatric Database from 2005 to 2014 were included and followed until death, emigration, or study termination (31.12.2015). Data on Barthel Index (BI) were used to assess ADL. Patients were categorized into four predefined standard BI subcategories according to the national Danish version of the statistical classification of diseases [BI = 0-24 (very low ADL), BI = 25-49 (low ADL), BI = 50-79 (moderate reduced ADL), and BI = 80-100 (independent ADL)]. Association with mortality was assessed using multivariable Cox regression analysis adjusting for age, marital status, Charlson Comorbidity Index, BMI, prior hospitalizations, year of admission and polypharmacy. RESULTS: In total, 6550 patients (women 62%) were included, median (IQR) age 84 (79-88) years and BI 37 (13-63). Mortality increased significantly with decreasing BI in both the crude and multivariable analysis. In subcategories BI = (80-100) and BI = (0-24), survival time (median (95%)) was 3.6 (3.4-3.9) years and 0.8 (0.7-0.9) years, respectively. Also, in patients with BI = (0-24), the overall mortality risk (HR (95% CI)) was 2.5 (2.2-2.8), 30-day risk 11.8 (5.8-23.9), and 1-year risk 4.4 (3.6-5.5) when using BI = (80-100) as reference. CONCLUSION: Barthel Index is independently associated with all-cause mortality among older patients with dementia admitted to hospital. BI may be a helpful tool for clinicians when discussing treatment and care strategies with patients and their families.

Barthel Index at hospital admission is associated with mortality in geriatric patients: a Danish nationwide population-based cohort study.

PURPOSE: The Barthel Index (BI)-100 is used to measure geriatric patients' activities of daily living (ADL). The aim of this study was to explore whether BI at hospital admission is associated with mortality. PATIENTS AND METHODS: In a nationwide population-based cohort study, patients aged ≥65 years admitted during 2005-2014 to Danish geriatric departments were assessed with BI at admission. Data were entered into the Danish National Database of Geriatrics and linked at the individual level to the Danish health registers (Civil Registration System, National Patient Register, and National Database of Reimbursed Prescriptions). The BI was categorized into four predefined standard subcategories according to the national Danish version of the statistical classification of diseases (BI =80-100 [independent ADL], BI =50-79 [moderate reduced ADL], BI =25-49 [low ADL], and BI =0-24 [very low ADL]). Patients were followed until death, emigration, or end of the study (December 31, 2015). Associations with mortality adjusted for age, admission year, marital status, body mass index, Charlson comorbidity index, polypharmacy, and hospitalizations during the preceding year were analyzed by multivariable Cox regression analysis. RESULTS: Totally, 74,603 patients were included. Women (63%) were older than men (mean [SD] age; 83 [7] vs 81 [7] years) and had higher BI (median [IQR]; 55 [30-77] vs 52 [26-77]). Median survival (years [95% CI]) was lowest in the subcategory "BI =0-24" in both women (1.3 [1.2-1.4]) and men (0.9 [0.8-0.9]). Adjusted mortalities (HR [95% CI]; reference BI =80-100) in women were 2.41 (2.31-2.51) for BI =0-24, 1.66 (1.60-1.73) for BI =25-49, and 1.34 (1.29-1.39) for BI =50-79 and in men were 2.07 (1.97-2.18) for BI =0-24, 1.58 (1.51-1.66) for BI =25-49, and 1.29 (1.23-1.35) for BI =50-79. CONCLUSION: BI at admission is strongly and independently associated with mortality in geriatric patients. BI has the potential to provide useful supplementary information for the planning of treatment and future care of older patients.

Birth cohort differences in the prevalence of longevity-associated variants in APOE and FOXO3A in Danish long-lived individuals.

Gene variants found to associate with human longevity in one population rarely replicate in other populations. The lack of consistent findings may partly be explained by genetic heterogeneity among long-lived individuals due to cohort differences in survival probability. In most high-income countries the probability of reaching e.g. 100years increases by 50-100% per decade, i.e. there is far less selection in more recent cohorts. Here we investigate the cohort specificity of variants in the APOE and FOXO3A genes by comparing the frequencies of the APOE ε4 allele and the minor alleles of two variants in FOXO3A at age 95+ and 100+ in 2712 individuals from the genetically homogeneous Danish birth cohorts 1895-96, 1905, 1910-11, and 1915. Generally, we find a decrease in the allele frequencies of the investigated APOE and FOXO3A variants in individuals from more recent birth cohorts. Assuming a recessive model, this negative trend is significant in 95+ year old individuals homozygous for the APOE ε4 allele (P=0.026) or for the FOXO3A rs7762395 minor allele (P=0.048). For the APOE ε4 allele, the significance is further strengthened when restricting to women (P=0.006). Supportive, but non-significant, trends are found for two of the three tested variants in individuals older than 100years. Altogether, this indicates that cohort differences in selection pressure on survival to the highest ages are reflected in the prevalence of longevity gene variants. Although the effect seems to be moderate, our findings could have an impact on genetic studies of human longevity.

Key considerations for preventing suicide in older adults: consensus opinions of an expert panel.

BACKGROUND: The number of older adults is growing rapidly. This fact, combined with the high rates of suicide in later life, indicates that many more older adults will die by their own hands before rigorous trials can be conducted to fully understand the best approaches to prevent late life suicide. AIMS: To disseminate key considerations for interventions addressing senior suicidal behavior. METHODS: An international expert panel has reviewed and discussed key considerations for interventions against suicide in older adults based on existing evidence, where available, and expert opinion. RESULTS: A set of new key considerations is divided into: universal, selective, and indicated prevention as well as a section on general considerations. CONCLUSIONS: The suggestions span a wide range and are offered for consideration by local groups preparing new interventions, as well as large scale public health care planning.

No association between telomere length and survival among the elderly and oldest old.

BACKGROUND: The consistent findings of a negative correlation between telomere length and replicative potential of cultured cells, as well as a decreasing telomere length in a number of different tissues in humans with age, have led to the suggestion that telomeres play a role in cellular aging in vivo and ultimately even in organismal aging. Furthermore, one small longitudinal study of elderly individuals has suggested that longer telomeres are associated with better survival. METHODS: Telomere length was measured as mean terminal restriction fragment length on blood cells from 812 persons, age 73 to 101 years, who participated in population-based surveys in 1997-1998. Among the participants were 652 twins. The participants were followed up through the Danish Civil Registration system until January 2005, at which time 412 (51%) were dead. RESULTS: Univariate Cox regression analyses revealed that longer telomeres were associated with better survival (hazard ratios = 0.89 [95% confidence interval = 0.76-1.04] per 1 kb in males and 0.79 [0.72-0.88] per 1 kb in females, respectively). However, including age in the analyses changed the estimates to 0.97 (0.83-1.14) and 0.93 (0.85-1.03), respectively. Intrapair comparison showed that among 175 twin pairs in which at least one died during follow up, it was the twin with the shorter telomere length who died first in 97 (55%) of the pairs (95% confidence interval = 48-63%). We could not confirm the recently reported negative correlation between telomere length and obesity or between telomere length and smoking. CONCLUSION: This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.

The tumor necrosis factor alpha -308G>A polymorphism is associated with dementia in the oldest old.

OBJECTIVES: To test the hypothesis that the tumor necrosis factor (TNF) -308 G>A promoter gene polymorphism is a risk factor in age-related dementia and longevity. DESIGN: A cross-sectional and a longitudinal study. SETTING: A population-based sample of Danish centenarians. PARTICIPANTS: One hundred-year-old Danes (n=122) from "The Longitudinal Study of Danish Centenarians." Octogenarians (n=174) and healthy volunteers aged 18 to 30 (n=47) served as reference groups. METHODS: Whether the distribution of TNF -308 GG/GA/AA genotypes were different in centenarians than in younger age groups was investigated (Fischer exact test). Furthermore, whether the TNF -308 G>A polymorphism was associated with the prevalence of dementia (logistic regression analysis), the plasma level of TNF-alpha (analysis of variance), and mortality in the following 5 years (Cox regression analysis) within the cohort of centenarians was tested. RESULTS: The distribution of TNF -308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF-alpha, but the significance was questionable due to a low number of subjects with this genotype. CONCLUSION: It is possible that the TNF -308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism possess the optimal inflammatory response with regard to protection against age-related neurodegeneration.

Elevated levels of tumor necrosis factor alpha and mortality in centenarians.

BACKGROUND: Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) alpha initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-alpha was also a prognostic marker for all-cause mortality in these persons. METHODS: We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-alpha, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during the subsequent 5 years. RESULTS: Only 9 subjects were alive after 5 years. Elevated levels of TNF-alpha were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C-reactive protein were not associated with mortality when levels of TNF-alpha were included in the analysis. Dementia and cardiovascular diseases represented the major causes of comorbid conditions at baseline. TNF-alpha was still associated with mortality in multivariate models that included these parameters as confounders. CONCLUSION: TNF-alpha was an independent prognostic marker for mortality in persons aged 100 years, suggesting that it has specific biological effects and is a marker of frailty in the very elderly.

High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes.

BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age. An increased percentage and number of T lymphocytes from the 81 year olds expressed TNF-alpha, whereas centenarians did not show this altered TNF-alpha secretion profile. CONCLUSION: T cells may contribute to the elevated levels of plasma TNF-alpha in healthy elderly subjects, whereas other mechanisms are responsible in very old individuals.

Hyponatraemia in very old nonhospitalised people: association with drug use.

OBJECTIVE: Hyponatraemia is one of the major problems in geriatric inpatients. However, in nonhospitalised elderly, the preponderance of hyponatraemia and the importance of the effect of drug intake on serum sodium concentrations are little known. This study investigated the prevalence of hyponatraemia in very old nonhospitalised people, controlling for factors that may induce hyponatraemia (especially drug use). METHODS: Data on serum sodium concentration, health and drug use were retrieved for 185 persons aged 92 to 93 years (the 1905 cohort) and 147 persons aged 100 years (the centenarian cohort) participating in two major population-based studies of elderly people in Denmark. Data were analysed by comparing median serum sodium concentrations between users and nonusers of various drugs after controlling for the influence of age, sex, cancer, heart failure, hypothyroidism, renal failure and smoking. Furthermore, the preponderance of drug use in the patients with clinically relevant hyponatraemia was compared with that in persons with normal serum sodium concentrations. RESULTS: Median serum sodium concentration was 140 mmol/L for the centenarians and 141 mmol/L for the 1905 cohort. In total, 19 persons had hyponatraemia (serum sodium concentration < or =134 mmol/L). There was no association between median serum sodium concentration and any of the above-mentioned diseases, or sex or smoking. Of the drugs generally known to cause hyponatraemia, only omeprazole and oral antidiabetic agents were associated with significantly lower median serum sodium concentrations (difference 3 mmol/L). Use of thiazide diuretics was significantly more common than expected in persons with hyponatraemia compared with persons with a normal serum sodium concentration (7 of 19 vs 46 of 270 individuals). Furthermore, the results suggested that digoxin and lactulose might be associated with a lowered median serum sodium concentration. CONCLUSION: This study demonstrates that severe hyponatraemia was rarely seen in a population-based sample of very old persons and that drugs have only a limited influence on serum sodium concentration. The only drug class associated with clinically relevant hyponatraemia was thiazide diuretics, which were used by significantly more persons with hyponatraemia. Furthermore, this study suggests that digoxin and lactulose use is associated with lower serum sodium concentrations in the elderly.

Proinflammatory cytokines, antibodies to Chlamydia pneumoniae and age-associated diseases in Danish centenarians: is there a link?

Plasma levels of tumour necrosis factor (TNF)-alpha levels increase with age. High levels are associated with dementia and atherosclerosis in centenarians. Chlamydia pneumoniae induces the production of proinflammatory cytokines and has been related to the pathogeneses of Alzheimer's disease and cardiovascular diseases. The purpose of this study was to test the hypothesis that circulating levels of TNF-alpha represent a link between C. pneumoniae, high prevalences of dementia and cardiovascular diseases in 126 Danish centenarians. IgA antibody titres against C. pneumoniae were linearly correlated with high plasma levels of TNF-alpha in centenarians. However, both parameters were also correlated with total IgA in the blood and the association between C. pneumoniae IgA and TNF-alpha was not significant when total IgA was included in a multiple linear regression model. Accordingly, the association between C. pneumoniae-specific IgA and TNF-alpha may reflect immune activation rather than a specific antibody response. No associations were found between antibodies to C. pneumoniae and dementia or cardiovascular diseases. Although TNF-alpha is likely to be involved in the pathogenesis of atherosclerosis and dementia, the present study does not support the hypothesis that TNF-alpha represents a link between chronic C. pneumoniae infection and these disorders.