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PubMed1999

Risk stratification for cardiac valve replacement. National Cardiac Surgery Database. Database Committee of The Society of Thoracic Surgeons.

BACKGROUND: The Society of Thoracic Surgeons National Database Committee is committed to risk stratification and assessment as integral elements in the practice of cardiac operations. The National Cardiac Surgery Database was created to analyze data from subscribing institutions across the country. We analyzed the database for valve replacement procedures with and without coronary artery bypass grafting to determine trends in risk stratification. METHODS: The database contains complete records of 86,580 patients who had valve replacement procedures at the participating institutions between 1986 and 1995, inclusive. The 1995 harvest of data was conducted in late 1996 and available for evaluation in 1997. These records were used to conduct an in-depth analysis of risk factors associated with valve replacement and to provide prediction of operative death by using regression analysis. Regression models were made for six subgroups. RESULTS: Adverse patient risk factors, including diabetes, hypertension and reoperation, but not ventricular function, increased over time. There were trends with regard to increasing age of the various population subsets. The types of prostheses used remained similar over time, with more mechanical prostheses than bioprostheses used for both aortic and mitral valve replacement. There was a trend toward increased use of bioprostheses in aortic replacements and decreased use in mitral replacements between 1991 and 1995 than between 1986 and 1990. The mortality rate was determined by patient subset for primary operation and reoperation and by urgency status. The modeling showed that the predicted and observed mortality correlated for all age groups and within patient subsets. CONCLUSIONS: Risk modeling is a valuable tool for predicting the probability of operative death in any individual patient. This large, multiinstitutional database is capable of determining modern operative risk and should provide standards for acceptable care. The study illustrates the importance of risk stratification for early death both for the patient and the surgeon.

Adult↗

PubMed2003

Population stratification and spurious allelic association.

Great efforts and expense have been expended in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Concomitantly, technology for detection and scoring of single nucleotide polymorphisms (SNPs) has undergone rapid development, extensive catalogues of SNPs across the genome have been constructed, and SNPs have been increasingly used as a means for investigation of the genetic causes of complex human diseases. For many diseases, population-based studies of unrelated individuals--in which case-control and cohort studies serve as standard designs for genetic association analysis--can be the most practical and powerful approach. However, extensive debate has arisen about optimum study design, and considerable concern has been expressed that these approaches are prone to population stratification, which can lead to biased or spurious results. Over the past decade, a great shift has been noted, away from case-control and cohort studies, towards family-based association designs. These designs have fewer problems with population stratification but have greater genotyping and sampling requirements, and data can be difficult or impossible to gather. We discuss past evidence for population stratification on genotype-phenotype association studies, review methods to detect and account for it, and present suggestions for future study design and analysis.

Alleles↗

PubMed2003

Social stratification, development and health in Pakistan: an empirical exploration of relationships in population-based national health examination survey data.

There is a growing literature on an overall direct relationship between health and social position in developed countries. The relationship, however, is less well documented in developing countries where social hierarchies are changing more rapidly, demographic and health transitions are less advanced, and this topic has received less attention from researchers than in some developed countries. This paper presents an empirical investigation of the relationship between social stratification and social development and population health using data on over 6000 adults from the National Health Survey of Pakistan, a nationally representative health examination survey of people in that country. We analyze four indicators of poor nutrition in adults from this data set. The findings reveal complex relationships among social development, social stratification and the consequences for the health of the people of Pakistan. Underweight is related to economic status, anemia to education and social development, and both severe dental caries and a monotonous diet are related to both development and economic status which interact with each other. These results suggest that continued conceptual refinement and the development of standardized measures of stratification and development would contribute to building cross-nationally comparable data sets addressing issues of the relationship among health and economic development and health transitions.

Adolescent↗

PubMed1997

Female life expectancy, gender stratification, health status, and level of economic development: a cross-national study of less developed countries.

A number of studies have attempted to account for cross-national differences in life expectancy, but relatively few have focused on female life expectancy, and even fewer on the relevance of predictors linked to gender stratification theory. The present study seeks to assess the utility of gender stratification theory in accounting for cross-national differences in female life expectancy in less developed countries. An incremental model building strategy is used to develop a final model that combines predictors linked to both industrialism theory and gender stratification theory. The analysis is based on multiple regression and cross-sectional samples that vary in size from 40 to 97 countries. Evidence is presented that several aspects of women's status have a positive effect on female life expectancy. Indicators of women's educational status, women's economic status, and women's reproductive autonomy all prove to be important predictors of female life expectancy. Analysis of interaction effects suggests that the strength of the effects of some aspects of women's economic status and the effect of some aspects of health status on female life expectancy vary with the level of economic development. A comprehensive assessment of the relative strength of alternative measures of women's education is carried out, and evidence is presented that it does make a difference how the level of women's education is measured.

Adolescent↗

PubMed2003

[Emergency room risk stratification of patients with chest pain without ST segment elevation].

OBJECTIVES: To investigate the prognostic factors in patients who come to the emergency room with chest pain but without ST segment elevation. PATIENTS AND METHOD: 743 consecutive patients were evaluated by recording clinical history, electrocardiogram and troponin I determination, and early (<24 h) exercise testing was done for the low-risk subgroup of patients (n=203). All patients were followed during 3 months for major events (acute myocardial infarction or death). RESULTS: Major events occurred in 71 patients (9.6%). Multivariate analysis (C statistic=0.79; 95% CI 0.73-0.84; p=0.0001) identified the following predictors: age > or =72 years (OR=1.7; 95% CI, 1.0-2.9; p=0.05), insulin-dependent diabetes mellitus (OR=2.9; 95% CI, 1.5-5.4; p=0.001), previous ischemic heart disease (OR=1.9; 95% CI, 1.1-3.2; p=0.02), ST depression (OR=2.1; 95% CI, 1.2-3.8; p=0.01) and troponin I elevation (OR=2.9; 95% CI, 1.5-5.3; p=0.001). These five predictors were used to construct a risk score based on their odds ratios, which allowed event rate stratification by quartiles of the score: 0-2 points (1.6% events), 3-4 points (8.1% events), 5-7 points (11.9% events) and > or =8 points (26.2% events); p=0.0001. No patient with negative findings in the early exercise testing had major events. CONCLUSIONS: In patients with chest pain, the combination of clinical, electrocardiographic and biochemical data available on admission to the emergency service allows rapid prognostic stratification. Early exercise testing is advisable for the final stratification of low risk patients.

Aged↗

PubMed2001

Use of risk stratification to identify patients with unstable angina likeliest to benefit from an invasive versus conservative management strategy.

OBJECTIVES: This study was designed to determine whether patient characteristics collected at presentation can identify which patients benefit from immediate coronary angiography and revascularization. BACKGROUND: Risk stratification may offer a method for identifying which patients with unstable angina or non-Q-wave myocardial infarction (NQMI) are likeliest to benefit from invasive management strategies. METHODS: The analysis was based on data from a randomized controlled trial that enrolled 1,473 patients presenting with unstable angina or NQMI who were randomly assigned to an early invasive or early conservative (medical) management strategy. We constructed a risk-stratification score for each patient based on adjusted odds ratios for clinical variables likely to predict adverse outcomes. We stratified all trial subjects by their risk scores and studied the rates of death or myocardial infarction (MI) of the early invasive management strategy in each stratum. RESULTS: The final multivariate model included older age, ST segment depression on presentation, history of complicated angina before presentation, and elevation in baseline creatine kinase-MB fraction. Although patients with a higher risk score had an increased rate of death or MI within 42 days and 365 days (p < 0.001) in both management strategies, early invasive management for patients in the high and very high risk categories was associated with a lower rate of death or MI within 42 days compared with conservative management. No such benefit was seen in patients in the larger group of patients in the very low, low or moderate risk categories (p = 0.03 for the interaction between risk category and management assignment). CONCLUSIONS: Risk stratification may be an effective method for identifying those patients with unstable angina or NQMI most likely to benefit from early invasive management. Selective use of early invasive management can have a substantial impact in reducing morbidity and mortality in higher risk patients, but may not be warranted in lower risk patients.

Aged↗

PubMed2002

N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation.

OBJECTIVES: The study evaluated the prognostic value of single measurement of N-terminal pro brain natriuretic peptide (NT-proBNP) obtained on admission in patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation. BACKGROUND: Patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation constitute a large and heterogeneous population. Early risk stratification has been based on clinical background factors, electrocardiography (ECG) and biochemical markers of myocardial damage. The neurohormonal activation has, so far, received less attention. METHODS: The NT-proBNP was analyzed on admission in 755 patients admitted because of chest pain and no ST-segment elevation. Patients were followed concerning death for 40 months (median). RESULTS: The median NT-proBNP level was 400 (111 to 1646) ng/l. Compared to the lowest quartile, patients in the second, third and fourth quartiles had a relative risk of subsequent death of 4.2 (1.6 to 11.1), 10.7 (4.2 to 26.8) and 26.6 (10.8 to 65.5), respectively. When NT-proBNP was added to a Cox regression model including clinical background factors, ECG and troponin T, the NT-proBNP levels were independently associated with prognosis. CONCLUSIONS: A single measurement of NT-proBNP on admission will substantially improve the early risk stratification of patients with symptoms suggestive of an acute coronary syndrome and no ST-segment elevation. A combination of clinical background factors, ECG, troponin T and NT-proBNP obtained on admission will provide a highly discerning tool for risk stratification and further clinical decisions.

Aged↗

PubMed2002

Prognostic use of human leukocyte antigen genotyping for rheumatoid arthritis susceptibility, disease course, and clinical stratification.

HLA markers of the class II region are important for determination of the predisposition to RA, clinical manifestations, and rate of progression of joint destruction in this autoimmune disease. Furthermore, evidence emerges indicating that HLA markers also have an impact on treatment outcome in RA. Currently, several immunopathogenetic models of HLA-dependent influences in RA are under debate. These models insufficiently explain the graded influence of HLA-DR and HLA-DQ on manifestation and joint destruction, however. Currently, there is not enough evidence to unequivocally identify a primary susceptibility locus or to pinpoint the HLA-dependent mechanism in RA. Overall, the influence of HLA class II markers on disease susceptibility is rather restricted, and, in turn, their utility in establishing the diagnosis of RA is of limited use. Although relative risks are higher for the association of particular genotypes with extra-articular forms of RA, HLA genotyping may not contribute to prognostication in individual patients but may aid in disease stratification. In contrast, HLA genotyping in early RA, particularly when combined with the determination of RFs and determination of the presence of bony erosions, is of value to identify patients at risk for poor outcome. In turn, these patients may benefit from early aggressive therapy, and HLA genotyping should be useful to aid in risk stratification in patients and thus helpful for the choice of treatment. Lastly, disease and risk stratification based on HLA markers along with the elucidation of HLA-dependent mechanisms may facilitate the development of specific immunotherapy modalities.

Arthritis, Rheumatoid↗

PubMed1999

A simple approach to risk stratification in adult heart transplantation.

OBJECTIVE: While there are numerous reports in the literature of risk factors for graft failure after heart transplantation, simple models for risk stratification are lacking. This study describes a simple method for risk stratification in adult heart transplantation that can be applied when the size of a dataset is insufficient for formal regression modelling. METHODS: Multi-centre prospective cohort study. Fourteen risk factors documented in the literature as increasing post transplant graft failure were used to formulate a model. Risk factors included in the model were recipient age >50 years, pre-operative ventilatory support, pre-operative circulatory support, >1 previous sternotomy, pulmonary vascular resistance >2.5 wood units, male with body surface area >2.5 m2, retransplant, ischaemic time >3.5 h, donor age >45 years, donor inotropic support >10 microg/kg per min dopamine, female donor, ratio donor/recipient body surface area <0.7, donor with diabetes and history of donor drug abuse. Four risk groups were defined depending on the number of risk factors present: Low, none; moderate, 1; high, 2 or 3; very high, 4 or more. Graft survival to 30 days was chosen as the primary outcome. The model was tested on 373 adult transplants performed in the UK between April 1995 and December 1996. RESULTS: Twenty eight transplants were low risk, 82 moderate, 201 high and 62 very high. The 30-day survival (70% CI) for the risk groups was low, 97% (93-100), moderate 95% (92-98), high 87% (84-89) and very high 80% (75-83) (P = 0.02). CONCLUSIONS: This preliminary model enables some stratification of heart transplant procedures according to donor and recipient risk profile. Further work will be directed at refining and validating the model.

Adult↗

PubMed2000

Expression of the HB9 homeobox gene concomitant with proliferation accompanying epidermal stratification during development of chick embryonic tarsometatarsal skin.

A homeobox gene, HB9, has been isolated from the tarsometatarsal skin of 13-day-old chick embryos using a degenerate RT-PCR-based screening method. In situ hybridization analysis revealed that, during development of chick embryonic skin, the HB9 gene was expressed in epidermal basal cells of the placodes, but not in those of interplacodes, and in the dermal cells under the placodes at 9 days before addition of an intermediate layer by proliferation of the basal cells in the placodes. With the onset of epidermal stratification, the direction of the basal cell mitosis changed, with the axis becoming vertical to the epidermal surface. Placodes and interplacodes form outer and inner scales, respectively, after they have elongated distally (Tanaka S, Kato Y (1983b) J Exp Zool 225: 271-283). During scale ridge elongation at 12-15 days, HB9 was strongly expressed in the epidermis of the outer scale face, where the cell proliferation is more active than in the epidermis of the inner scale face; hence, stratification of the outer scale face is more prominent than that of the inner scale face. After 16 days, when mitotic activity in the epidermal basal cells decreases and the thickness of the epidermis is maintained at a constant level, the HB9 expression decreases with the onset of epidermal keratinization. These results suggest that HB9 may be involved in the proliferation of the epidermal basal cells that accompanies epidermal stratification.

Animals↗

PubMed2001

Stratification analysis of MICA triplet repeat polymorphisms and HLA antigens associated with ulcerative colitis in Japanese.

We previously reported a conserved haplotype of HLA B52-DR2 and a significantly high frequency of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane-short tandem repeat (TM-STR) 6 allele in Japanese patients with ulcerative colitis (UC). To examine the predominance of the MICA TM-STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC was estimated following stratification of the patients to control for any possible confounding effects of other alleles positively associated with UC. Sixty-four patients with UC and 236 unrelated healthy controls were included in this study. All subjects were Japanese. HLA-A, -B, -C, and -DR antigens were determined serologically. A triplet repeat polymorphism of the MICA was determined by direct sequencing. To control for the effect of linkage disequilibrium, Mantel-Haenszel weighed odds ratios were calculated. Significantly higher phenotype frequencies of B52, MICA TM-STR 6, and DR2 were observed in patients with UC. Linkage disequilibria among alleles associated with UC revealed that a B52 - MICA TM-STR 6 - DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA-B52 was estimated after patient stratification for the possible confounding effect of MICA TM-STR 6 or DR2, a strong significant association of B52 with UC was still observed. In contrast, no association with UC was observed for MICA TM-STR 6 or DR2, after stratification of the possible confounding effect of HLA-B52. These results imply that the significant increase in MICA TM-STR 6 in Japanese patients with UC is attributable to linkage disequilibrium with HLA-B52.

Colitis, Ulcerative↗

PubMed1993

Stratification of ON and OFF ganglion cell dendrites depends on glutamate-mediated afferent activity in the developing retina.

A fundamental attribute of the vertebrate visual system is the segregation of ON and OFF pathways signalling increments and decrements of light. In the mature retina, dendrites of ON- and OFF-centre retinal ganglion cells (RGCs) stratify in different sublaminae of the inner plexiform layer (IPL), and are differentially innervated by two types of bipolar cells which depolarize and hyperpolarize on exposure to light. This stratification of ON and OFF RGCs is achieved by the gradual restriction of their dendrites which ramify throughout the IPL early in development. The factors underlying this regressive event are unknown. Dendritic stratification occurs around the time that bipolar cells form synapses in the IPL, which raises the possibility that synaptic activity is involved in this process. Here we test this hypothesis by treating the developing cat retina with the glutamate analogue 2-amino-4-phosphonobutyric acid (APB), which hyperpolarizes ON cone bipolar and rod bipolar cells, thereby preventing their release of glutamate. We report that intraocular injection of APB during the period when dendritic stratification normally occurs prevents the formation of structurally segregated ON and OFF retinal pathways. These results provide evidence that glutamate-mediated afferent activity regulates the remodelling of RGC dendrites during development.

Aminobutyrates↗

PubMed2005

Asymmetric cell divisions promote stratification and differentiation of mammalian skin.

The epidermis is a stratified squamous epithelium forming the barrier that excludes harmful microbes and retains body fluids. To perform these functions, proliferative basal cells in the innermost layer periodically detach from an underlying basement membrane of extracellular matrix, move outward and eventually die. Once suprabasal, cells stop dividing and enter a differentiation programme to form the barrier. The mechanism of stratification is poorly understood. Although studies in vitro have led to the view that stratification occurs through the delamination and subsequent movement of epidermal cells, most culture conditions favour keratinocytes that lack the polarity and cuboidal morphology of basal keratinocytes in tissue. These features could be important in considering an alternative mechanism, that stratification occurs through asymmetric cell divisions in which the mitotic spindle orients perpendicularly to the basement membrane. Here we show that basal epidermal cells use their polarity to divide asymmetrically, generating a committed suprabasal cell and a proliferative basal cell. We further demonstrate that integrins and cadherins are essential for the apical localization of atypical protein kinase C, the Par3-LGN-Inscuteable complex and NuMA-dynactin to align the spindle.

Animals↗

PubMed2006

Epidermal morphogenesis: the transcriptional program of human keratinocytes during stratification.

The epidermis serves to protect the body against environmental assaults and at the same time is able to survive and replenish itself under harsh conditions. The epidermis accomplishes this feat via a well-orchestrated program of stratification and terminal differentiation that provides barrier against infection, radiation, and water loss. Despite significant progress in skin biology, many molecules and pathways that are involved in stratification and barrier formation remain unknown. Here, we employed tissue-engineered models of complete versus impaired epidermal stratification to discover the genes that may be important in this process. Transcriptional profiling at different stages of development showed significant differences in transcription, signaling, and most important metabolism-associated genes between fully stratified and poorly stratified epithelia. These transcriptional changes correlated well with functional data on cell proliferation, expression of adhesion molecules, and utilization of metabolic pathways, ultimately leading to different phenotypes. Our data identified genes that were not previously known to play a role in epidermis and established a link between metabolism and morphogenesis in skin epithelium.

Carbohydrate Metabolism↗

PubMed1999

The long-term culture of porcine urothelial cells and induction of urothelial stratification.

OBJECTIVE: To assess porcine urothelial cell cultures and the in vitro induction of urothelial stratification in long-term cultures, to study their morphological, functional and genetic behaviour, and thus provide potential autologous urothelium for tissue-engineered substitutes for demucosalized gastric or colonic tissue. MATERIALS AND METHODS: Primary cultures of porcine urothelium were established and the cells passaged thereafter. Cell specificity was confirmed by cytokeratin analysis, cell membrane stability assessed using lactate dehydrogenase leakage, cell de-differentiation by gamma-glutamyl transferase activity and genomic stability by karyotype investigations. Histology and scanning electron microscopy were performed to study the cultured cells and the stratified constructs. Furthermore, collagen matrices were tested as cell scaffolds. RESULTS: The cells were cultured for 180 days; 10 subcultures were established during this period. Stratification was induced in a culture flask and on a collagen matrix. Cytokeratins 7, 8, 17 and 18 were expressed in all cultures, and cell membranes were stable, with no evident de-differentiation. The cultures were stable in their genotype and no chromosomal aberrations were found. The histology and immunohistochemistry of the stratified porcine constructs, and cell membrane stability and cell de-differentiation, were compared with those in the human system. CONCLUSION: Pig and human urothelial cells can be cultured over a long period with no signs of senescence. Urothelial stratification can be induced in vitro. The collagen matrix seems to be an excellent scaffold, allowing cell adherence and growth.

Animals↗

PubMed2000

Prospective evaluation of 3 risk stratification scores in cardiac surgery.

BACKGROUND: The aim of the study was to evaluate 3 different risk stratification scores in cardiac surgery, based on the hospital results of 1,299 patients. METHODS: From June 1995 to December 1997, all patients (n = 1,299) undergoing coronary artery bypass grafting (CABG) and/or heart valve surgery were prospectively enrolled. The postoperative in-hospital outcome (mortality, morbidity and length of hospital stay) was analysed in relation to three different risk stratification scores (Parsonnet, Higgins and French score). RESULTS: The results of 1,299 patients (mean age 62.8 +/- 10.2 years) were analysed. 10 patients died, accounting for a total mortality of 0.8%. 13 patients (1%) underwent cardiopulmonary resuscitation. In 25 patients (1.9%), perioperative myocardial infarction occurred. Performance of the 3 systems was assessed by evaluating discrimination with receiver operating characteristic (ROC) curves. The area under the ROC curve was 0.761 for Parsonnet, 0.786 for Higgins and 0.798 for French score. The French and the Higgins score showed an increase of in-hospital mortality, morbidity and length of stay in relation to increasing risk classes. CONCLUSION: For objective evaluation of the outcome in cardiac surgery, case-mix severity needs to be considered, which is reflected by preoperative risk stratification scores. In our study, all the 3 scores showed a high discrimination and are appropriate tools to assess mortality in cardiac surgery. Especially the French and the Higgins score (restricted to 5 groups), due to their simplicity, were useful to predict postoperative outcome in clinical routine.

Adolescent↗

PubMed2000

Enhanced prognostic stratification of patients with left ventricular hypertrophy with the use of single-photon emission computed tomography.

BACKGROUND: Patients with left ventricular hypertrophy (LVH) are at increased risk of future cardiovascular events. Little is known about risk stratification of these patients with the use of myocardial perfusion imaging. This study sought to assess the prognostic stratification of patients with LVH by using myocardial perfusion single-photon emission computed tomography (SPECT). METHODS AND RESULTS: We studied 633 consecutive patients with electrocardiographic evidence of LVH who underwent dual isotope myocardial perfusion SPECT (rest thallium 201/stress technetium 99m sestamibi) and were followed up for a mean period of 22 +/- 7 months. During the follow-up period, 67 events (35 cardiac deaths and 32 nonfatal myocardial infarctions) occurred (6% annual event rate). The results of the perfusion scan significantly risk-stratified the population; patients with normal scans had a low rate of nonfatal myocardial infarction and cardiac death (<1% per year of follow-up). The rates of cardiac events increased significantly as a function of the scan result: 4.9% in patients with mildly abnormal scans and 10. 3% in moderately to severely abnormal scans. Cox proportional hazards analysis demonstrated that after adjusting for pretest likelihood of coronary artery disease (the most predictive clinical variable; chi(2) = 15.5, P <.001), summed stress score (the most predictive nuclear variable; chi(2) = 18, P <.0001) added significant incremental prognostic information (global chi(2) increased from 15.5 to 36; P <.001). CONCLUSIONS: In patients with LVH with an overall high cardiac event rate, SPECT provided enhanced stratification by adding significant incremental prognostic information over clinical and historic variables.

Aged↗

PubMed2001

Post-myocardial infarction risk stratification in elderly patients.

BACKGROUND: The purpose of this study was to examine the use of post-myocardial infarction (MI) risk stratification in the elderly. Although expert panels have recommended risk stratification after MI, limited data are available on whether patients actually undergo suggested testing. In particular, concern has been raised that the elderly, who are at high risk for recurrent ischemia and short-term death, are not referred as often as younger patients for post-MI testing. METHODS: We studied the records of 192,311 Medicare patients (age > or = 65 years) admitted with MI between January 1992 and November 1992. By combining Medicare part A and part B data, we created a longitudinal record of patient care within 60 days of an MI admission. We describe the pattern of post-MI testing for ischemia and left ventricular function and outcomes as a function of patient age. RESULTS: Patients > or = 75 years of age were significantly less likely than patients 65 to 74 years of age to have either cardiac catheterization (17% vs 43%) or any test for coronary artery disease severity (24% vs 53%). They were also less likely to have a test of left ventricular function (61% vs 76%). Even after adjustment for baseline characteristics, older patients remained less likely than younger patients to have an assessment of coronary artery disease severity (odds ratio, 0.44) or left ventricular function (odds ratio, 0.65). CONCLUSIONS: Post-MI risk stratification declines with age and falls short of recommendations in our nation's elderly. This lack of testing may result in lost opportunities for therapeutic interventions in this high-risk group.

Aged↗