Accumulation Of Comorbidities Research Articles

Women With a History of Preeclampsia Exhibit Accelerated Aging and Unfavorable Profiles of Senescence Markers.

Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho (P=0.018); increased leptin (P=0.016) and leptin/adiponectin ratio (P=0.027), and increased extracellular vesicles positive for tissue factor (P=0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment (P=0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women (P=0.003). Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia.

1901 Determinants of hospital readmissions in older people with dementia: A scoping review

Abstract Introduction In the UK, fifty-three percent of hospitalised older people with dementia have multimorbidity, and are at an increased risk of hospital readmission within 30 days from discharge. Between 20-40% of these readmissions are preventable [1]. Current research focused on the biological causes of readmissions. However, older people with dementia have additional psychosocial factors increasing their risk of readmission. The aim of this scoping review was to identify psychosocial determinants within the context of known biological factors. Methods Electronic databases MEDLINE, EMBASE, CINAHL and PsychInfo were searched from inception until July 2022. Quantitative and qualitative studies in English including adults aged 65 years and over with dementia, their care workers and informal carers were considered if they investigated readmission. An inductive approach was adopted to map determinants of hospital readmission. Identified themes were described as narrative categories. Results Seventeen studies including 7,194,878 participants met our inclusion criteria from a total of 4736 articles. Sixteen quantitative studies included observational cohort and randomised controlled trial designs. One American study was qualitative. Ten studies were based in the USA, and one study each from Taiwan, Australia, Canada, Sweden, Japan, Denmark, and The Netherlands. Large hospital and insurance records provided data in over 2 million patients in one American study. Identified psychosocial determinants included inadequate hospital discharge planning, limited interdisciplinary collaboration, and socioeconomic inequalities among ethnic minorities. Biological determinants included reduced mobility and accumulation of comorbidities. Use of antipsychotic medications might explain the interplay between biological and psychosocial determinants. Conclusion Poorly defined roles and responsibilities of health and social care professionals and poor communication during care transitions increase the risk of readmission in older people with dementia. Reference 1. Godard-Sebillotte C, Strumpf E, Sourial N, et al. L. Primary care continuity and potentially avoidable hospitalization in persons with dementia. J Am Geriatr Soc. 2021;69(5):1208-20.

Clustering of cardiovascular and renal comorbidities and risk of incident atrial fibrillation in the community-based PREVEND cohort

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The PREVEND study is supported by the Dutch Kidney Foundation and the Netherlands Heart Foundation. Background Atrial fibrillation (AF) is a condition that occurs in the presence of comorbidities. With the accumulation of comorbidities over time, certain comorbidities may more often occur together than others, i.e. clustering of comorbidities. Acknowledging clustering of certain comorbidities may have implications for diagnosing previously unrecognized comorbidities, and clusters of comorbidities may carry differential risks of diseases, like AF. Albeit that the individual cardiovascular risk factors and comorbidities are well known, information on the impact of clustering of these on incident AF is sparse. Purpose We aimed to investigate the presence of clusters of cardiovascular and renal comorbidities and study the association between comorbidity clusters and incident AF. Methods We used the community-based Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort in which 8,592 individuals participated. We excluded individuals with prior AF or missing ECG data, leaving 8,265 individuals for analysis. Atrial fibrillation was diagnosed if either AF or atrial flutter was present on a 12-lead ECG during one of the study visits, or at an outpatient visit or hospitalization. Latent class analysis was performed to assess clustering of 10 cardiovascular and renal comorbidities. The optimum number of classes was determined by the number of classes for which the Bayesian information criterion (BIC) reached a minimum value. As secondary analysis, latent class analysis was repeated with additionally including age, sex, and ethnicity. Kaplan-Meier analysis was performed to calculate the cumulative probability of incident AF, stratified by the latent classes. Results In the total population, the mean age was 48.9±12.6 years and 50.2% were women. During 9.2±2.1 years of follow-up, 251 individuals (3.0%) developed AF. Latent class analysis resulted in a model with three clusters as the optimal model, with one cluster being young (44.5±10.8 years) and healthy, carrying a low (1.0%) risk of incident AF; one cluster being older (63.0±8.4 years) and multimorbid, carrying a high (16.2%) risk of incident AF and a third middle-aged (57.0±11.3 years), obese and hypertensive cluster carrying an intermediate risk (5.9%) of incident AF. When adding age, sex and ethnicity to the latent class analysis, similar results were observed. Conclusion We identified three clusters of individuals in the community-based PREVEND cohort. The three clusters contained different amounts of comorbidities carrying different risks of incident AF. However, there were no differences between clusters regarding specific combination(s) of comorbidities.

Clinical and Sociodemographic Predictors of Mortality in End-Stage Renal Disease Inpatients in Rural Areas of the USA: Evidence From the Nationwide Inpatient Sample.

Background: End-stage renal disease (ESRD) has been associated with an increase in all-cause mortality among patients. The accumulation of comorbidities appears to be a contributing factor. This study set out to identify the effect of comorbidity severity and other predictors of mortality among ESRD inpatients in rural America.Methods: This is a cross-sectional study that used the 2016-2018 Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP). The study included patients aged 18 years or older with ESRD hospitalized in rural hospitals in America. Independent variables used in the survey include age, gender, race, type of admission (elective versus nonelective), type of hospital control, expected primary payer, and severity of comorbidities. The dependent variable was death during hospitalization. All analyses were weighted. Univariate (frequencies), bivariate (Chi-square), and logistic regression analyses were done using the SAS Studio (SAS Institute Inc., Cary, NC, USA).Results: There were 144,575 weighted ESRD hospitalizations, and 5% of the hospitalized patients died. In the bivariate analysis, significant variables include age group, race, type of hospital admission, expected primary payer, type of hospital control, and severity of comorbidities, and all had a significant P-value of <0.0001. On multivariable logistic regression analysis, middle-aged and elderly patients had 40% (adjusted odds ratio (AOR): 1.40, 95% confidence interval (CI): 1.20-1.62) and 201% (AOR: 3.01, 95% CI: 2.61-3.48) more odds of mortality while hospitalized, respectively, compared to the young. Compared to whites, blacks had 19% (AOR: 0.81, 95% CI: 0.77-0.86) reduced odds of mortality, Hispanics had 47% (AOR: 0.53, 95% CI: 0.46-0.61) reduced odds of mortality, Native Americans had 27% (AOR: 0.73, 95% CI: 0.63-0.84) reduced odds of mortality, and Asian or Pacific Islanders had 30% (AOR: 0.70, 95% CI: 0.54-0.90) reduced odds of mortality. ESRD patients on nonelective hospitalizations had 16% (AOR: 0.84, 95% CI: 0.79-0.90) reduced odds of mortality while hospitalized versus those on elective hospitalization. ESRD patients with severe comorbidities had 40% (AOR: 1.40, 95% CI: 1.26-1.54) more odds of mortality compared to those with mild comorbidities, and those with moderate comorbidities had 22% (AOR: 1.22, 95% CI: 1.10-1.36) compared to those with mild comorbidities. Compared to patients on Medicare, ESRD hospitalizations on Medicaid had 19% (AOR: 1.19, 95% CI: 1.06-1.32) higher odds of mortality, hospitalizations on private insurance had 26% (AOR: 1.26, 96% CI: 1.15-1.37) higher odds of mortality, self-pay patients had 99% (AOR: 1.99, 95% CI: 1.61-2.45) higher odds of mortality, and no charge patients had over 1400% (AOR: 15.61, 95% CI: 7.09-34.35) higher odds of mortality. The area under the curve (AUC) for the model was 62%.Conclusion: The severity of comorbidities and expected primary payer are the modifiable predictors identified to predict ESRD inpatient mortality. From this study, the findings suggest that strategies aimed at preventing the severity of comorbidities and ensuring universal health coverage might help reduce ESRD inpatient mortality in rural America.

Divergent age-related humoral correlates of protection against respiratory syncytial virus infection in older and young adults: a pilot, controlled, human infection challenge model

Respiratory viral infections are typically more severe in older adults. Older adults are more vulnerable to infection and do not respond effectively to vaccines due to a combination of immunosenescence, so-called inflamm-ageing, and accumulation of comorbidities. Although age-related changes in immune responses have been described, the causes of this enhanced respiratory disease in older adults remain poorly understood. We therefore performed volunteer challenge with respiratory syncytial virus (RSV) in groups of younger and older adult volunteers. The aim of this study was to establish the safety and tolerability of this model and define age-related clinical, virological, and immunological outcomes. In this human infection challenge pilot study, adults aged 18-55 years and 60-75 years were assessed for enrolment using protocol-defined inclusion and exclusion criteria. Symptoms were documented by self-completed diaries and viral load determined by quantitative PCR of nasal lavage. Peripheral blood B cell frequencies were measured by enzyme-linked immunospot and antibodies against pre-fusion and post-fusion, NP, and G proteins in the blood and upper respiratory tract were measured. The study was registered with ClinicalTrials.gov, NCT03728413. 381 adults aged 60-75 years (older cohort) and 19 adults aged 18-55 years (young cohort) were assessed for enrolment using protocol-defined inclusion and exclusion criteria between Nov 12, 2018, and Feb 26, 2020. 12 healthy volunteers aged 60-75 years and 21 aged 18-55 years were inoculated intranasally with RSV Memphis-37. Nine (67%) of the 12 older volunteers became infected, developing mild-to-moderate upper respiratory tract symptoms that resolved without serious adverse events or sequelae. Viral load peaked on day 6 post-inoculation and symptoms peaked between days 6 and 8. Increases in circulating IgG-positive and IgA-positive antigen-specific plasmablasts, serum neutralising antibodies, and pre-F specific IgG were similar younger and older adults. However, in contrast to young participants, secretory IgA titres in older volunteers failed to increase during infection and, unlike serum IgG, did not correlate with protection. Better understanding of age-related differences in clinical outcomes and immune correlates of protection can overcome reduction in vaccine efficacy with advancing age. We identify correlates of protection in older adults, revealing previously unrecognised factors which might have implications for targeted vaccine discovery and drug development in this vulnerable group. Medical Research Council and GlaxoSmithKline EMINENT Consortium.

Clinical Comorbidity Phenotype in Knee Osteoarthritis is Associated With Higher Intensity Scores

Knee osteoarthritis (OA) is a common osteoarticular disease. Its prevalence increases with age, as well as the coexistence of other chronic diseases. Recent research has revealed an association between OA and cardiovascular diseases. However, the association between knee OA and comorbidities has not been fully studied. Therefore, the purpose of this study was to investigate the association between knee OA and comorbidities. In this cross-sectional study, patients with knee OA were enrolled. Sociodemographic data, as well as comorbidities, were collected. Grading of knee OA was performed using the Kellgren-Lawrence (KL) grading system. The functional impact of knee OA was assessed by KOOS-Physical Function Shortform (KOOS-PS). This study assessed 104 patients with knee OA (10 men and 94 women). The mean age was 65.83±11.08 years. Mean VAS pain was 6.56±1.72. Mean KOOS-PS was 15.58±6.73. Up to 81 patients (77.9%) had severe knee OA, according to the KL grading system. Comorbidity was noted in 92 cases (88%). The most frequent comorbidities were obesity (62.5%), hypertension (61.5%), and dyslipidemia (43.3%). Comorbidities in knee OA were associated with age (P=0.04), axial deviation in the sagittal plane (P=0.01), neuropathic pain component (P=0.02), and VAS pain (P=0.04). Our study also showed a significant correlation between comorbidities and structural grading of knee OA (P=0.04). However, comorbidities were not correlated with the KOOS-PS score (P=0.06). The accumulation of comorbidities is significantly associated with higher intensity scores in knee OA. Physicians should additionally pay close attention to the prevention and treatment of comorbidities in the routine management of OA.

Heart failure clinical care analysis uncovers risk reduction opportunities for preserved ejection fraction subtype

Heart failure (HF) has no cure and, for HF with preserved ejection fraction (HFpEF), no life-extending treatments. Defining the clinical epidemiology of HF could facilitate earlier identification of high-risk individuals. We define the clinical epidemiology of HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]), identified among 2.7 million individuals receiving routine clinical care. Differences in patterns and rates of accumulation of comorbidities, frequency of hospitalization, use of specialty care, were defined for each HF subtype. Among 28,156 HF cases, 8322 (30%) were HFpEF and 11,677 (42%) were HFrEF. HFpEF was the more prevalent subtype among older women. 177 Phenotypes differentially associated with HFpEF versus HFrEF. HFrEF was more frequently associated with diagnoses related to ischemic cardiac injury while HFpEF was associated more with non-cardiac comorbidities and HF symptoms. These comorbidity patterns were frequently present 3 years prior to a HFpEF diagnosis. HF subtypes demonstrated distinct patterns of clinical co-morbidities and disease progression. For HFpEF, these comorbidities were often non-cardiac and manifested prior to the onset of a HF diagnosis. Recognizing these comorbidity patterns, along the care continuum, may present a window of opportunity to identify individuals at risk for developing incident HFpEF.

Supracricoid laryngectomy: the impact of senescence on swallowing safety.

ABSTRACT:Objective:To investigate the association between aging and the functional aspects of swallowing (laryngeal penetration and laryngotracheal aspiration) in individuals who underwent supracricoid laryngectomy in the late period and without complaints.Methods:A total of 70 patients, 56 (80%) aged >60 years and 14 (20%) <60 years, under outpatient follow-up, after cancer treatment and with no complaints of swallowing, performed functional evaluation using the swallowing videofluoroscopy. Image classification was performed using the penetration-aspiration scale developed by Rosenbek. The χ2 test and logistic regression were applied to associate the age categories to the outcomes (penetration and aspiration).Results:Patients aged over 60 years had a higher prevalence of penetration (24.29%) and aspiration (48.57%) than patients aged under 60 years. In this sample, aspiration was associated with age. Patients aged over 60 years were more likely to present penetration (27% more) during swallowing than patients under 60 years. Patients aged over 60 years had an approximately four-fold greater probability of laryngotracheal aspiration than patients aged under 60 years.Conclusion:In patients without complaints of swallowing in the late postoperative period of supracricoid laryngectomy, there is a greater probability of laryngotracheal aspiration in elderly aged over 60 years than in individuals under 60 years.

153 Age and the Extent of Chest Radiographic Findings in Hospitalized Patients with COVID 19

IntroductionSince the emergence of COVID 19 in December 2019, its clinical and radiological features are still being discovered and their prognostic implications evaluated. Chest X-ray (CXR) typically shows patchy or diffuse asymmetric airspace opacities. Regardless of the different classifications of radiological findings that have been used, it is becoming clear that multi-lobar changes in the lungs are associated with poorer outcomes than single lobar involvement or minimal/no radiological abnormalities.Aim: To assess the correlation of age with the extent of CXR findings in hospitalized COVID 19 patients.MethodsA retrospective, cross-sectional analysis was carried out on inpatients with RT-PCR confirmed COVID 19. Chest X-ray findings were classified as minimal/no radiological changes, single lobar opacification and multi-lobar changes (involving 2 or more lobes and/or ARDS changes). SPSS 26 software was used for statistical analysis. Spearman’s correlation and linear regression were used to assess correlation.Results211 patients were included in the analysis; 124 males and 87 females. Mean age of the patients was 72.4 years; SD +/−16.15. There was significant positive correlation between age and degree and extent of radiological changes in all patients (r = 0.367; p < 0.01). This correlation persisted even when broken down by gender (r = 0.448; p < 0.01) for males and (r = 0.322; p < 0.01) for females. Discussion: Older age has been repeatedly reported as a risk factor for poor prognosis in COVID 19. The main findings of COVID-19 on CXR are those of atypical or organizing pneumonia. Older people tend to have more extensive involvement of the lungs. There could be many explanations for the CXR correlation with age including the diminished cardiovascular reserve with ageing, the accumulation of comorbidities and decreased or abnormal immune response.ConclusionAge significantly correlate with the extent of chest radiographic findings in inpatients with COVID 19.

A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities

BackgroundThe elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16–18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span.Materials and methodsOld (24–26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1–21) and mice with scores ≥5 were considered to have important comorbidities.ResultsOverall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.ConclusionsEven in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.

Increased risk profile in the treatment of patients with symptomatic degenerative aortic valve stenosis over the last 10 years.

IntroductionCurrently, Cardiology Centres are overfilled with patients with degenerative aortic valve stenosis (DAS), usually eldery, with severe concommittant comorbidities, who are referred for further decisions and possible intervention.AimTo evaluate changes in the risk profile of patients with severe DAS admitted to the cardiology department a decade ago compared with patients currently being admitted.Material and methodsWe retrospectively evaluated all patients admitted with confirmed severe DAS, hospitalized during 2005–2006 (group I: 140 patients) and in 2016 (group II: 152 patients), admitted for aortic valve intervention. A standard transthoracic echocardiogram, cardiovascular symptom and risk factor distribution, perioperative risk with the logistic EuroSCORE II and STS mortality scores were obtained.ResultsPatients in group II were significantly older (p < 0.001), had more cardiovascular risk factors, and more often presented with atrial fibrillation (27% vs. 11.4%, p = 0.001), renal impairment (34.9% vs. 22.8%; p = 0.024), severe lung disease (17.1% vs. 2.1%, p < 0.001), and extracardiac arteriopathy (40.1% vs. 17.8%, p < 0.001). The aortic valve area (AVA) (p = 0.356), mean-transvalvular pressure gradient (p = 0.215), and left ventricular ejection fraction (p = 0.768) were similar in both groups. However, the prevalence of pulmonary hypertension, severe mitral regurgitation, and low-flow, low-gradient DAS were 3.1-, 8.4- and 1.84-fold more frequent in group II than group I. The percentages of subjects with EuroSCORE II and STS scores ≥ 4% in 2005–2006 were 7.1% and 6.4%, as compared to 27% and 26.3% in 2016 (both p < 0.001). 22% of patients in 2016, as compared to 31% in 2005/2006, were considered ineligible for DAS intervention.ConclusionsIn just a decade, the risk profile of patients admitted with DAS has increased hugely, mainly due to older age, accumulation of comorbidities and more advanced disease at presentation. Although transcatheter aortic valve intervention has expanded the indications for intervention in high-risk patients, the number of patients disqualified from interventional treatment remains high.

Prophylaxis and treatment of infections in elderly patients with rheumatism

In general, the risk of serious infections increases with age, mainly explained by immunosenescence and accumulation of comorbidities. Those patients with rheumatoid arthritis who are of advanced age and require treatment with immunosuppressive agents are at particular risk to develop an infectious disease. Actual requirement and kind of treatment on the one hand, and risk of infection on the other hand, have to be considered carefully for each patient. For example, in high-risk patients, it is important to use glucocorticoids in a minimal way, i.e. in low doses and as short as possible. Vaccination, especially against influenza and pneumococci, plays an essential role in preventing infectious diseases, particularly in the elderly. Nevertheless, in cases of suspected bacterial infection, empiric antibiotic therapy should be started promptly. Due to the burden of drugs taken by patients of advanced age, the benefits and possible side effects as well as potential drug interactions have to be carefully considered. In summary, drug treatment of the elderly requires bearing in mind the complete health status of the individual patient.