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PubMedDate not supplied

[Pharmacokinetics of naftidrofuryl in multimorbidity in geriatric patients].

The present pharmacokinetic study of a drug used in geriatric patients with multiple diseases reveals that the half-life in the elderly was extended for about three times as long as in the corresponding control group. There are significant positive as well as negative correlations between the kinetic data and routine parameters of the metabolism. These statistical correlations should be controlled by experimental studies.

Aged↗
PubMedDate not supplied

[Furosemide--pharmacokinetics in geriatric patients with multimorbidity].

20 geriatric patients with multiple diseases were administered a single intravenous dose of 40 mg furosemide. Furosemide plasma and urine concentrations were measured using a thin-layer chromatography method (25) and were fitted to an open 2-compartment model. Furosemide half-life was prolonged twofold in the elderly patients compared with a control group of younger adults. In the same way renal clearance and total clearance were markedly reduced in the geriatric group. The nonrenal clearance and the volume of distribution (beta) were not significantly altered. There were many significant correlations between clinical and biochemical data and pharmacokinetic parameters, especially between blood pressure and the area under the curve (AUC 0-infinity), total clearance and nonrenal clearance of furosemide. Our data suggest a special function of alpha-2-globulins in binding of furosemide. Renal function (i.e. creatinine clearance) was shown to be an important parameter for estimating the elimination rate of furosemide.

Aged↗
PubMed1998

[Obesity: entrance port to multimorbidity].

Obesity is an essential risk factor for hypertension, coronary heart disease and stroke as well as for metabolic disturbances, especially for type 2 diabetes, hyper- and dyslipidemia, and it is responsible for the metabolic syndrome with insulin resistance and hyperinsulinemia. Disturbances in the lung function are also induced by obesity, as a higher risk for arthrosis on the lower extremities. Some oncological diseases like breast-, endometrial-, and prostatic cancer are associated with obesity. It is evident, that the fat distribution plays an important role in the development of obesity associated diseases: the accumulation of visceral fat has a higher risk as the peripheral fat, probably due to the different metabolism.

Body Composition↗
PubMed2006

Carotid-artery stenting in a high-risk patient population--single centre, single operator results.

AIMS: The aim of this study was to assess the outcome of carotid-artery stenting (CAS) in high-risk patients in routine clinical settings while excluding the impact of multiple operators and the learning curve of individual operators on the outcome, and to determine the impact of individual risk factors, including vascular multimorbidity, on the outcome. METHODS AND RESULTS: A total of 143 consecutive patients, 100 (69.9%) males and 43 (30.1%) females, mean age 68.7+/-8 years treated between February 1999 and May 2004 in the Heart Centre Coswig by a single operator for a symptomatic (n=37) and asymptomatic (n=106) on average greater than 70% (82.3+/-10.7%) or 80% (85.0+/-9.1%) NASCET carotid-artery stenosis, respectively, were studied. At least one NASCET exclusion criteria was present in 140 patients (97.9%), and vascular multimorbidity was present in 94 (65.7%) patients. In 28 (19.6%) patients there was a complete occlusion of the contralateral internal carotid artery and in 12 (8.4%) patients the procedure was performed prior to emergency coronary bypass surgery. In all, 47 (32.9%) procedures were performed without and 96 (67.1%) were performed with thromboembolic protection. Technical success was achieved in all patients. Combined neurological complications, TIA, PRIND and stroke, occurred in 5 (3.5%) patients, of which 3 (2.1%) were PRIND and 2 (1.4%) were strokes. The neurological complications were more frequent and more severe in symptomatic patients compared to asymptomatic patients (PRIND 2.7% vs 1.9%; stroke 0% vs 5.4%). In patients in whom thromboembolic protection was used, the rate of neurological complications was lower compared to those without protection (PRIND 1.0% vs 4.3%; stroke 1.0% vs. 2.1%). There was no death related to the procedure. Neurological complications were more frequent and more severe in patients with vascular multimorbidity compared to those with an isolated carotid-artery stenosis (4.2% vs 2.0%). The rate of neurological complications was similar in type II diabetics and nondiabetics (2.9% vs 4.1%). In 4.2%, minor complications related to the arterial puncture site were observed (3.5% hematoma not requiring blood transfusion, 0.7% pseudoaneurysm). At follow-up after a minimum of 6 months, 9 (6.3%) patients had died, the majority of whom had died of cardiovascular disease (3.5%). CONCLUSIONS: CAS can be performed with an acceptable risk in high-risk patients in routine clinical settings when it is performed by an experienced operator. The use of thromboembolic protection devices reduces the risk of neurological complications. Presence of vascular multimorbidity, but not diabetes, appears to increase the risk of all causes and of neurological complications.

Aged↗
PubMed2006

Psychiatric morbidity is related to a chain of prenatal and perinatal adversities.

BACKGROUND: Most studies on the effects of early risk factors on future mental health focus on specific obstetric complications as risk factors for specific disorders. However, obstetric complications rarely occur in isolation, and the same holds for psychiatric problems. AIMS: To study prenatal and perinatal risk factors for psychiatric multimorbidity in early adulthood and to determine whether these differ from risk factors for monomorbidity. STUDY DESIGN: Monomorbidity and multimorbidity of six types of psychiatric disorders were determined by a standardised psychiatric interview. Using univariate and multivariate logistic and ordinal logistic regression, associations of mono- and multimorbidity with prospectively collected early risk factors were examined. SUBJECTS: Two hundred and eighty-five young adults selected from a prospective birth cohort on the basis of their Obstetric Optimality Scores. OUTCOME MEASURES: Six types of psychiatric disorder and their co-occurrence. RESULTS: Monomorbidity was related to isolated early risk factors such as low birth weight or a low Apgar score, and to an accumulation of unfavourable pre- and perinatal events. Multimorbidity on the other hand, was only related to a chain of pre- and perinatal adversities. CONCLUSION: Research and prevention strategies should not focus solely on isolated early risk factors, but also on the entire pre- and perinatal situation.

Adult↗
PubMedDate not supplied

Pharmacokinetics of alprazolam in elderly patients with multiple diseases.

The pharmacokinetics of alprazolam (1 mg p.o.) were investigated (using a new developed HPLC-assay) in 10 multimorbid elderly patients (five female, five male; mean age 72.8 +/- 8.2 years, creatinine clearance 63.6 +/- 25.9 ml/min, weight 68.9 +/- 13.9 kg). Compared with young and elderly volunteers from other studies peak plasma concentrations of alprazolam were decreased while peak time and elimination half-life were increased. 'Second peak' plasma levels (correlated with age and creatinine clearance) occurred in eight of 10 elderly patients. The variability associated with the pharmacokinetic parameters in the multimorbid elderly patients was far greater than that observed in young and old healthy volunteers. Mean alprazolam concentrations in multimorbid patients aged 72 years or more were elevated as compared to 'younger' patients (age range: 63-71 years). Dose reduction should be considered in the older multimorbid patients.

Journal Article↗
PubMed2026

Unraveling 'F' factor: towards a genetic-clinical framework for the musculoskeletal-heart crosstalk in metabolic aging.

BACKGROUND: The rising co-occurrence of cardiometabolic diseases and musculoskeletal degeneration poses a critical challenge to healthy aging, yet the shared biological mechanisms underlying this multimorbidity remain poorly defined. This study aimed to establish an integrative clinical-genetic framework to elucidate the common frailty factor, the 'F' factor, that captures the systemic vulnerability linking cardiometabolic multimorbidity (CMM) and musculoskeletal aging. METHODS: Utilizing the prospective China Health and Retirement Longitudinal Study (CHARLS) cohort, we developed and validated novel Frailty-Integrated Indices for CMM risk prediction, evaluated with machine learning models interpreted via SHapley Additive exPlanations (SHAP). Independently, we applied genomic structural equation modeling (Genomic-SEM) to integrate genome-wide association data from six traits-coronary artery disease, type 2 diabetes, hypertension, bone mineral density, frailty, and telomere length-to model a shared latent genetic factor ('F' factor). This was followed by multivariate GWAS, fine-mapping, transcriptome-wide association study (TWAS), gene-based analysis, and functional annotation to prioritize causal genes, pathways, and cell types. RESULTS: Clinically, several Frailty-Integrated Indices significantly improved CMM risk prediction, with the optimal model achieving an AUC of 0.727. Genetically, we modeled a significant shared latent genetic factor ('F' factor), pinpointing novel risk loci and implicating key genes such as APOE and SLC22A3. These genes were enriched in pathways including cellular senescence and cholesterol metabolism and showed specific expression patterns in developmental brain stages and across multi-organ endothelial cells. CONCLUSION: Our findings provide converging evidence for Musculoskeletal‑Heart crosstalk of metabolic aging and inferred the 'F' factor as a genetic correlate of a transdiagnostic state, which links genetic predisposition to metabolic dysregulation, and systemic functional decline. This work provides a multi-level biological characterization of multimorbidity liability, informing early-risk detection and preventive strategies for complex aging-related comorbidities.

Humans↗
PubMed2002

Quantifying psychiatric comorbidity--lessions from chronic disease epidemiology.

BACKGROUND: Comorbidity research in psychiatric epidemiology mostly uses measures of association like odds or risk ratios to express how strongly disorders are linked. In contrast, chronic disease epidemiologists increasingly use measures of clustering, like multimorbidity (cluster) coefficients, to study comorbidity. This article compares measures of association and clustering. METHODS: Narrative review, algebraical examples, a secondary analysis of an existing dataset and a pooled analysis of published data. RESULTS: Odds and risk ratios, but the former more than the latter, confound clustering with coincidental comorbidity. Multimorbidity coefficients provide a pure estimate of clustering which is the proportion of the association between disorders that is of etiological interest. Odds and risk ratios can express comorbidity between no more than two disorders, whilst clustering coefficients, although computationally laboursome, can capture multimorbidity of any number of disorders. Cluster coefficients depend less on the prevalence of illness in study groups than measures of association. CONCLUSION: Odds and risk ratios are well suited for comorbidity research which focuses on which sets of disorders or syndromes tend to occur in combination and the implications of this for, for instance, nosological classification, a traditional interest of psychiatric epidemiology. However, the cluster coefficient is to be preferred if the interest is more aetiological, addressing for example why certain individuals are prone to multiple health problems.

Alcoholism↗
PubMed2001

Psychosocial patient characteristics and GP-registered chronic morbidity: a prospective study.

OBJECTIVE: The aim of this study was to get a profile of patients who are vulnerable to get multiple chronic, recurrent or high-impact diseases in a limited time period. We studied the incidence rates of morbidity and multimorbidity, and the influence of psychosocial characteristics on their occurrences. METHOD: Cohort study with 3551 subjects. Baseline measurement of psychosocial characteristics and a 2-year follow-up period for morbidity. The relations were evaluated using multiple logistic regression analysis. RESULTS: After adjustment for basic socio-demographic variables, a high internal locus of control belief was found to be protective [odds ratio (OR)=0.82] for the occurrence of morbidity, negative life events increased the risk (OR=1.22). Characteristics specifically protective for the occurrence of multimorbidity as compared to monomorbidity were: a high internal locus of control belief (OR=0.73), living as a couple or in a family as compared to living alone (OR=0.68) and a large social network (OR=0.41). CONCLUSION: It appears that certain patient characteristics are specifically related to the occurrence of multimorbidity. This provides opportunities for the future development of preventive interventions.

Adaptation, Psychological↗