Living Longer But Frailer? Temporal Trends in Life Expectancy and Frailty in Older Swedish Adults.

BACKGROUND: This study aims to examine temporal trends in frailty state transitions, and years spent frail, in older Swedish adults. METHODS: We followed the Swedish National Study on Aging and Care in Kungsholmen participants from baseline (2001-2004) for 15 (median: 9.6) years. A 40-deficit frailty index (FI) was constructed to identify 3 frailty states: robust (FI ≤ 0.125), mild frailty (0.125 < FI ≤ 0.25), and moderate and severe frailty (FI  > 0.25). Multistate survival analyses were implemented to obtain hazard ratios (HRs) for frailty state transitions, with birth year and sex as predictors. To examine temporal trends, frailty state-specific life expectancies at age 60 were forecasted for robust persons born in different years (1900, 1910, 1920, 1930, and 1940), also by sex. RESULTS: At baseline, the 2 941 participants' mean age was 75 years and 65% were women. Predicted life expectancy and time spent frail from age 60 followed an increasing trend by birth year. Hazards of transitioning from mild frailty to death (HR: 0.89; 95% confidence interval [CI]: 0.83-0.97) and moderate and severe frailty to death (HR: 0.98; 95% CI: 0.97-1.00) were lower for those born later. Women were less likely to transition from robust to mild frailty (HR: 0.81; 95% CI: 0.70-0.93), mild frailty to moderate and severe frailty (HR: 0.80; 95% CI: 0.68-0.93), and moderate and severe frailty to death (HR: 0.68; 95% CI: 0.59-0.78), but spent more time frail. CONCLUSIONS: Our results point to an expansion of time spent frail among older Swedish adults over time.

Risk factors for multimorbidity in adulthood: A systematic review.

BACKGROUND: Multimorbidity, the coexistence of multiple chronic diseases in an individual, is highly prevalent and challenging for healthcare systems. However, its risk factors remain poorly understood. OBJECTIVE: To systematically review studies reporting multimorbidity risk factors. METHODS: A PRISMA-compliant systematic review was conducted, searching electronic databases (MEDLINE, EMBASE, Web of Science, Scopus). Inclusion criteria were studies addressing multimorbidity transitions, trajectories, continuous disease counts, and specific patterns. Non-human studies and participants under 18 were excluded. Associations between risk factors and multimorbidity onset were reported. RESULTS: Of 20,806 identified studies, 68 were included, with participants aged 18-105 from 23 countries. Nine risk factor categories were identified, including demographic, socioeconomic, and behavioral factors. Older age, low education, obesity, hypertension, depression, low pysical function were generally positively associated with multimorbidity. Results for factors like smoking, alcohol consumption, and dietary patterns were inconsistent. Study quality was moderate, with 16.2% having low risk of bias. CONCLUSIONS: Several risk factors seem to be consistently associated with an increased risk of accumulating chronic diseases over time. However, heterogeneity in settings, exposure and outcome, and baseline health of participants hampers robust conclusions.

Early Onset Delirium During Hospitalization Increases In-Hospital and Postdischarge Mortality in COVID-19 Patients: A Multicenter Prospective Study.

Objective: Delirium is a common feature in COVID-19 patients. Although its association with in-hospital mortality has previously been reported, data concerning postdischarge mortality and delirium subtypes are scarce. We evaluated the association between delirium and its subtypes and both in-hospital and postdischarge mortality.Methods: This multicenter longitudinal clinical-based study was conducted in Monza and Brescia, Italy. The study population included 1,324 patients (median age: 68 years) with COVID-19 admitted to 4 acute clinical wards in northern Italy during the first pandemic waves (February 2020 to January 2021). Delirium within 48 hours of hospital admission was assessed through validated scores and/or clinically according to DSM-5 criteria. The association of delirium-and its subtypes-with in-hospital and postdischarge mortality (over a median observation period of 257 [interquartile range: 189-410] days) was evaluated through Cox proportional hazards models.Results: The 223 patients (16.8%) presenting delirium had around 2-fold increased in-hospital (hazard ratio [HR] = 1.94; 95% CI, 1.38-2.73) and postdischarge (HR = 2.01; 95% CI, 1.48-2.73) mortality than those without delirium. All delirium subtypes were associated with greater risk of death compared to the absence of delirium, but hypoactive delirium revealed the strongest associations with both in-hospital (HR = 2.03; 95% CI, 1.32-3.13) and postdischarge (HR = 2.22; 95% CI, 1.52-3.26) mortality.Conclusions: In patients with COVID-19, early onset delirium is associated not only with in-hospital mortality but also with shorter postdischarge survival. This suggests that delirium detection and management are crucial to improving the prognosis of COVID-19 patients.Trial Registration: ClinicalTrials.gov identifier: NCT04412265.

Development and validation of an electronic database-based frailty index to predict mortality and hospitalization in a population-based study of adults with SARS-CoV-2.

Background: Electronic health databases are used to identify people at risk of poor outcomes. Using electronic regional health databases (e-RHD), we aimed to develop and validate a frailty index (FI), compare it with a clinically based FI, and assess its association with health outcomes in community-dwellers with SARS-CoV-2. Methods: Data retrieved from the Lombardy e-RHD were used to develop a 40-item FI (e-RHD-FI) in adults (i.e., aged ≥18 years) with a positive nasopharyngeal swab polymerase chain reaction test for SARS-CoV-2 by May 20, 2021. The considered deficits referred to the health status before SARS-CoV-2. The e-RHD-FI was validated against a clinically based FI (c-FI) obtained from a cohort of people hospitalized with COVID-19 and in-hospital mortality was evaluated. e-RHD-FI performance was evaluated to predict 30-day mortality, hospitalization, and 60-day COVID-19 WHO clinical progression scale, in Regional Health System beneficiaries with SARS-CoV-2. Results: We calculated the e-RHD-FI in 689,197 adults (51.9% females, median age 52 years). On the clinical cohort, e-RHD-FI correlated with c-FI and was significantly associated with in-hospital mortality. In a multivariable Cox model, adjusted for confounders, each 0.1-point increment of e-RHD-FI was associated with increased 30-day mortality (Hazard Ratio, HR 1.45, 99% Confidence Intervals, CI: 1.42-1.47), 30-day hospitalization (HR per 0.1-point increment = 1.47, 99%CI: 1.46-1.49), and WHO clinical progression scale (Odds Ratio = 1.84 of deteriorating by one category, 99%CI 1.80-1.87). Conclusion: The e-RHD-FI can predict 30-day mortality, 30-day hospitalization, and WHO clinical progression scale in a large population of community-dwellers with SARS-CoV-2 test positivity. Our findings support the need to assess frailty with e-RHD.

Instrumental evaluation of gait smoothness and history of falling in older persons: results from an exploratory case-control study.

Gait smoothness, perceived when a person walks continuously and uninterruptedly, is associated with an undisrupted gait pattern, good sensorimotor control, and a lower risk of falling. The spectral arc length (SPARC) is a quantitative metric proposed for the evaluation of movement smoothness from the signal obtained by wearable sensors. In this small exploratory case-control study, older persons with and without a history of injurious falls underwent a turn-test while wearing an accelerometer: gait smoothness was estimated by calculating SPARC during the straight and turning phases. Cases seemed to exhibit lower SPARC values during the turning phase, in comparison with control.

Frailty detection among primary care older patients through the Primary Care Frailty Index (PC-FI).

The prompt identification of frailty in primary care is the first step to offer personalized care to older individuals. We aimed to detect and quantify frailty among primary care older patients, by developing and validating a primary care frailty index (PC-FI) based on routinely collected health records and providing sex-specific frailty charts. The PC-FI was developed using data from 308,280 primary care patients ≥ 60 years old part of the Health Search Database (HSD) in Italy (baseline 2013-2019) and validated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; baseline 2001-2004), a well-characterized population-based cohort including 3363 individuals ≥ 60 years old. Potential health deficits part of the PC-FI were identified through ICD-9, ATC, and exemption codes and selected through an optimization algorithm (i.e., genetic algorithm), using all-cause mortality as the main outcome for the PC-FI development. The PC-FI association at 1, 3 and 5 years, and discriminative ability for mortality and hospitalization were tested in Cox models. The convergent validity with frailty-related measures was verified in SNAC-K. The following cut-offs were used to define absent, mild, moderate and severe frailty: < 0.07, 0.07-0.14, 0.14-0.21, and ≥ 0.21. Mean age of HSD and SNAC-K participants was 71.0 years (55.4% females). The PC-FI included 25 health deficits and showed an independent association with mortality (hazard ratio range 2.03-2.27; p < 0.05) and hospitalization (hazard ratio range 1.25-1.64; p < 0.05) and a fair-to-good discriminative ability (c-statistics range 0.74-0.84 for mortality and 0.59-0.69 for hospitalization). In HSD 34.2%, 10.9% and 3.8% were deemed mildly, moderately, and severely frail, respectively. In the SNAC-K cohort, the associations between PC-FI and mortality and hospitalization were stronger than in the HSD and PC-FI scores were associated with physical frailty (odds ratio 4.25 for each 0.1 increase; p < 0.05; area under the curve 0.84), poor physical performance, disability, injurious falls, and dementia. Almost 15% of primary care patients ≥ 60 years old are affected by moderate or severe frailty in Italy. We propose a reliable, automated, and easily implementable frailty index that can be used to screen the primary care population for frailty.

Health trajectories in older patients hospitalized for COVID-19: Results from the GeroCovid multicenter study.

BACKGROUND: COVID-19 has disproportionately affected older adults. Yet, healthcare trajectories experienced by older persons hospitalized for COVID-19 have not been investigated. This study aimed at estimating the probabilities of transitions between severity states in older adults admitted in COVID-19 acute wards and at identifying the factors associated with such dynamics. METHODS: COVID-19 patients aged ≥60 years hospitalized between March and December 2020 were involved in the multicentre GeroCovid project-acute wards substudy. Sociodemographic and health data were obtained from medical records. Clinical states during hospitalization were categorized on a seven-category scale, ranging from hospital discharge to death. Based on the transitions between these states, first, we defined patients' clinical course as positive (only improvements), negative (only worsening), or fluctuating (both improvements and worsening). Second, we focused on the single transitions between clinical states and estimated their probability (through multistage Markov modeling) and associated factors (with proportional intensity models). RESULTS: Of the 1024 included patients (mean age 78.1 years, 51.1% women), 637 (62.2%) had a positive, 66 (6.4%) had a fluctuating, and 321 (31.3%) had a negative clinical course. Patients with a fluctuating clinical course were younger, had better mobility and cognitive levels, fewer diseases, but a higher prevalence of cardiovascular disease and obesity. Considering the single transitions, the probability that older COVID-19 patients experienced clinical changes was higher within a 10-day timeframe, especially for milder clinical states. Older age, male sex, lower mobility level, multimorbidity, and hospitalization during the COVID-19 first wave (compared with the second one) were associated with an increased probability of progressing towards worse clinical states or with a lower recovery. CONCLUSION: COVID-19 in older inpatients has a complex and dynamic clinical course. Identifying individuals more likely to experience a fluctuating clinical course and sudden worsening may help organize healthcare resources and clinical management across settings at different care intensity levels.

Beyond Chronological Age: A Multidimensional Approach to Survival Prediction in Older Adults.

BACKGROUND: There is a growing interest in generating precise predictions of survival to improve the assessment of health and life-improving interventions. We aimed to (a) test if observable characteristics may provide a survival prediction independent of chronological age; (b) identify the most relevant predictors of survival; and (c) build a metric of multidimensional age. METHODS: Data from 3 095 individuals aged ≥60 from the Swedish National Study on Aging and Care in Kungsholmen. Eighty-three variables covering 5 domains (diseases, risk factors, sociodemographics, functional status, and blood tests) were tested in penalized Cox regressions to predict 18-year mortality. RESULTS: The best prediction of mortality at different follow-ups (area under the receiver operating characteristic curves [AUROCs] 0.878-0.909) was obtained when 15 variables from all 5 domains were tested simultaneously in a penalized Cox regression. Significant prediction improvements were observed when chronological age was included as a covariate for 15- but not for 5- and 10-year survival. When comparing individual domains, we find that a combination of functional characteristics (ie, gait speed, cognition) gave the most accurate prediction, with estimates similar to chronological age for 5- (AUROC 0.836) and 10-year (AUROC 0.830) survival. Finally, we built a multidimensional measure of age by regressing the predicted mortality risk on chronological age, which displayed a stronger correlation with time to death (R = -0.760) than chronological age (R = -0.660) and predicted mortality better than widely used geriatric indices. CONCLUSIONS: Combining easily accessible characteristics can help in building highly accurate survival models and multidimensional age metrics with potentially broad geriatric and biomedical applications.

Frailty, multimorbidity patterns and mortality in institutionalized older adults in Italy.

BACKGROUND: Little is known on how frailty influences clinical outcomes in persons with specific multimorbidity patterns. AIMS: To investigate the interplay between multimorbidity and frailty in the association with mortality in older individuals living in nursing homes (NH). METHODS: We considered 4,131 NH residents aged 60 years and over, assessed through the interRAI LTCF instrument between 2014 and 2018. Follow-up was until 2019. Considering four multimorbidity patterns identified via principal component analysis, subjects were stratified in tertiles (T) with respect to their loading values. Frailty Index (FI) considered 23 variables and a cut-off of 0.24 distinguished between high and low frailty levels. For each pattern, all possible combinations of tertiles and FI were evaluated. Their association (Hazard Ratio [HR] and 95% confidence interval) with mortality was tested in Cox regression models. RESULTS: In the heart diseases and dementia and sensory impairments patterns, the hazard of death increases progressively with patterns expression and frailty severity (being HR T3 vs. T1 = 2.36 [2.01-2.78]; HR T3 vs. T1 = 2.12 [1.83-2.47], respectively). In heart, respiratory and psychiatric diseases and diabetes, musculoskeletal and vascular diseases patterns, frailty seems to have a stronger impact on mortality than patterns' expression. DISCUSSION: Frailty increases mortality risk in all the patterns and provides additional prognostic information in NH residents with different multimorbidity patterns. CONCLUSIONS: These findings support the need to routinely assess frailty. Older people affected by specific groups of chronic diseases need a specific care approach and have high risk of negative health outcomes.

Technologies for the Instrumental Evaluation of Physical Function in Persons Affected by Chronic Obstructive Pulmonary Disease: A Systematic Review.

Several systems, sensors, and devices are now available for the instrumental evaluation of physical function in persons with Chronic Obstructive Pulmonary Disease (COPD). We aimed to systematically review the literature about such technologies. The literature search was conducted in all major scientific databases, including articles published between January 2001 and April 2022. Studies reporting measures derived from the instrumental assessment of physical function in individuals with COPD were included and were divided into application and validation studies. The quality of validation studies was assessed with the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) risk of bias tool. From 8752 articles retrieved, 21 application and 4 validation studies were included in the systematic review. Most application studies employed accelerometers, gait analysis systems, instrumented mattresses, or force plates to evaluate walking. Surface electro-myography or near-infrared spectroscopy were employed in four studies. Validation studies were heterogeneous and presented a risk of bias ranging from inadequate to doubtful. A variety of data regarding physical function can be retrieved from technologies used in COPD studies. However, a general lack of standardization and limitations in study design and sample size hinder the implementation of the instrumental evaluation of function in clinical practice.

Mechanical Ventilation in COVID-19 Patients: Insights into the Role of Age and Frailty from a Multicentre Observational Study.

In patients with COVID-19, frailty has been shown to better predict outcomes than age alone. We investigated factors associated with mechanical ventilation (MV) during hospitalization for COVID-19 among older adults in a multicentre study during the first two waves in Italy. Using data from the FRACOVID project, we included consecutive patients admitted to the participating centres during the first and second waves. We recorded sociodemographics, comorbidities, time since symptom onset, ventilatory support at admission, and chest X-ray findings. Frailty was assessed using a frailty index (FI). Results are reported as hazard ratios (HR) with 95%CI. 1,344 patients were included; 487 females (36.2%), median age 68 (56; 79) years; 52.4% had hypertension, 10.6% had chronic obstructive pulmonary disease, 15.2% were obese. Median FI was 0.088 (0.03, 0.20), and 67% had bilateral consolidations at admission. Median time since symptom onset was 7 days (4, 10). During hospitalization, 47 patients (3.6%, 95%CI 0.33-13.6%) received MV. Multivariable Cox regression analysis found that the likelihood of intubation decreased with increasing age (HR 0.945 (95%CI 0.921-0.969), p<0.0001), while heart rate >110bpm (HR 3.429 (95%CI 1.583-7.429), p=0.0018), and need for continuous positive airway pressure (CPAP) at admission (HR 2.626 (95%CI 1.330-5.186), p=0.0054) were significantly associated with a greater likelihood of intubation. Older patients are less likely to receive intubation, while those with heart rate >110 bpm and need for CPAP at admission are more likely to receive MV during hospitalization for COVID-19.

COVID-19 as an effect modifier of the relationship between age and in-hospital survival in older patients admitted to an Italian Emergency Department.

BACKGROUND: The SARS-CoV-2 pandemic modified how persons got into contact with emergency services, particularly during the first wave. AIM: The aim is to describe the characteristics of older persons with and without COVID-19 visiting the Emergency Department of a tertiary hospital and to investigate the impact of age on in-hospital survival in the two groups. METHODS: Patients older than 70 years were followed-up till discharge or in-hospital death. Cox regression models stratified by COVID-19 diagnosis were used to investigate survival. RESULTS: Out of 896 patients, 36.7% had COVID-19. Those without COVID-19 were older and affected by a higher number of chronic conditions but exhibited lower mortality (10.5 vs 48.1%). After the adjustment, age was associated with mortality only among those with COVID-19. DISCUSSION: COVID-19 modified the relationship between older age and in-hospital survival: whether this finding is explained by other biological vulnerabilities or by a selection of treatments based on age should be further investigated.

Multimorbidity Patterns and 5-Year Mortality in Institutionalized Older Adults.

OBJECTIVES: The aim was to characterize multimorbidity patterns in a large sample of older individuals living in nursing homes (NHs) and to investigate their association with mortality, also considering the effect of functional status. DESIGN: Observational and retrospective study. SETTING AND PARTICIPANTS: We analyzed data on 4131 NH residents in Italy, aged 60 years and older, assessed through the interRAI long-term care facility instrument. Entry date was between 2014 and 2018, and participants were followed until 2019. METHODS: Multimorbidity patterns were identified through principal component analysis; for the identified components, subjects were stratified in quintiles (Q) with respect to their loading values, with the higher quantiles indicating greater expression of the component's pattern. Their association [hazard ratio (HR) and 95% CI] with mortality was tested in Cox regression models. Analyses were stratified by disability status. RESULTS: Four patterns of multimorbidity were identified: (1) heart diseases; (2) dementia and sensory impairments; (3) heart, respiratory, and psychiatric diseases; and (4) diabetes, musculoskeletal, and vascular diseases. For the heart diseases pattern [HR Q5 vs Q1 = 1.83 (1.53-2.20)] and the dementia and sensory impairments pattern [HR Q5 vs Q1 = 1.23 (1.06-1.42)], as the specific multimorbidity expression increases, the risk of mortality increases. On stratifying by disability status, the association between the multimorbidity patterns and mortality was not always present. CONCLUSIONS AND IMPLICATIONS: Different multimorbidity patterns are differentially associated with mortality in older residents of NHs, confirming that multimorbidity's prognosis is strictly dependent on the underlying disease combinations. This knowledge may be useful to implement personalized preventive and therapeutic care pathways for institutionalized older adults, which respond to individuals' health needs.

The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017.

INTRODUCTION: Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. METHODS: The analyses were conducted employing the cross-sectional "Delirium Day" initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. RESULTS: A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09-2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p < 0.001]. DISCUSSION AND CONCLUSION: Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

The effect of frailty on in-hospital and medium-term mortality of patients with COronaVIrus Disease-19: the FRACOVID study.

BACKGROUND: Older people hospitalized for COVID-19 are at highest risk of death. Frailty Assessment can detect heterogeneity in risk among people of the same chronological age. We investigated the association between frailty and in-hospital and medium-term mortality in middle-aged and older adults with COVID-19 during the first two pandemic waves. METHODS: This study is an observational multicenter study. We recorded sociodemographic factors (age, sex), smoking status, date of symptom onset, biological data, need for supplemental oxygen, comorbidities, cognitive and functional status, in-hospital mortality. We calculated a Frailty Index (FI) as the ratio between deficits presented and total deficits considered for each patient (theoretical range 0-1). We also assessed the Clinical Frailty Scale (CFS). Mortality at follow-up was ascertained from a regional registry. RESULTS: In total, 1344 patients were included; median age 68 years (Q1-Q3, 56-79); 857 (64%) were men. Median CFS score was 3 (Q1-Q3 2-5) and was lower in younger vs. older patients. Median FI was 0.06 (Q1-Q3 0.03-0.09) and increased with increasing age. Overall, 244 (18%) patients died in-hospital and 288 (22%) over a median follow-up of 253 days. FI and CFS were significantly associated with risk of death. In two different models using the same covariates, each increment of 0.1 in FI increased the overall hazard of death by 35% (HR=1.35, 95%CI 1.23-1.48), similar to the hazard for each increment of CFS (HR=1.37, 95%CI 1.25-1.50). CONCLUSIONS: Frailty, assessed with the FI or CFS, predicts in-hospital and medium-term mortality and may help estimate vulnerability in middle-aged and older COVID-19 patients.

Special Issue-"Multimorbidity Development and Evolution: Clinical Implications".

Multimorbidity, the co-existence of multiple chronic diseases in the same individual, is not only extremely common in older persons but is also strongly associated with several poor health outcomes [...].

Comorbidity status of deceased COVID-19 in-patients in Italy.

BACKGROUND: Most COVID-19-related deaths have occurred in older persons with comorbidities. Specific patterns of comorbidities related to COVID-19 deaths have not been investigated. METHODS: A random sample of 6085 individuals in Italy who died in-hospital with confirmed COVID-19 between February and December 2020 were included. Observed to expected (O/E) ratios of disease pairs were computed and logistic regression models were used to determine the association between disease pairs with O/E values ≥ 1.5. RESULTS: Six pairs of diseases exhibited O/E values ≥ 1.5 and statistically significant higher odds of co-occurrence in the crude and adjusted analyses: (1) ischemic heart disease and atrial fibrillation, (2) atrial fibrillation and heart failure, (3) atrial fibrillation and stroke, (4) heart failure and COPD, (5) stroke and dementia, and (6) type 2 diabetes and obesity. CONCLUSION: In those deceased in-hospital due to COVID-19 in Italy, disease combinations defined by multiple cardio-respiratory, metabolic, and neuropsychiatric diseases occur more frequently than expected. This finding indicates a need to investigate the possible role of these clinical profiles in the chain of events that lead to death in individuals who have contracted SARS-CoV-2.

CT based radiomic approach on first line pembrolizumab in lung cancer.

Clinical evaluation poorly predicts outcomes in lung cancer treated with immunotherapy. The aim of the study is to assess whether CT-derived texture parameters can predict overall survival (OS) and progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) treated with first line Pembrolizumab. Twenty-one patients with NSLC were prospectively enrolled; they underwent contrast enhanced CT (CECT) at baseline and during Pembrolizumab treatment. Response to therapy was assessed both with clinical and iRECIST criteria. Two radiologists drew a volume of interest of the tumor at baseline CECT, extracting several texture parameters. ROC curves, a univariate Kaplan-Meyer analysis and Cox proportional analysis were performed to evaluate the prognostic value of texture analysis. Twelve (57%) patients showed partial response to therapy while nine (43%) had confirmed progressive disease. Among texture parameters, mean value of positive pixels (MPP) at fine and medium filters showed an AUC of 72% and 74% respectively (P < 0.001). Kaplan-Meyer analysis showed that MPP < 56.2 were significantly associated with lower OS and PFS (P < 0.0035). Cox proportional analysis showed a significant correlation between MPP4 and OS (P = 0.0038; HR = 0.89[CI 95%:0.83,0.96]). In conclusion, MPP could be used as predictive imaging biomarkers of OS and PFS in patients with NSLC with first line immune treatment.

Multimorbidity Patterns and 6-Year Risk of Institutionalization in Older Persons: The Role of Social Formal and Informal Care.

OBJECTIVES: The aim was to evaluate patterns of multimorbidity that increase the risk of institutionalization in older persons, also exploring the potential buffering effect of formal and informal care. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, Sweden. MEASURES: In total, 2571 community-dwelling older adults were grouped at baseline according to their underlying multimorbidity patterns, using a fuzzy c-means cluster algorithm, and followed up for 6 years to test the association between multimorbidity patterns and institutionalization. RESULTS: Six patterns of multimorbidity were identified: psychiatric diseases; cardiovascular diseases, anemia, and dementia; metabolic and sleep disorders; sensory impairments and cancer; musculoskeletal, respiratory, and gastrointestinal diseases; and an unspecific pattern including diseases of which none were overrepresented. In total, 110 (4.3%) participants were institutionalized during the follow-up, ranging from 1.7% in the metabolic and sleep disorders pattern to 8.4% in the cardiovascular diseases, anemia, and dementia pattern. Compared with the unspecific pattern, only the cardiovascular diseases, anemia, dementia pattern was significantly associated with institutionalization [relative risk ratio (RRR) = 2.23; 95% confidence interval (CI) 1.07‒4.65)], after adjusting for demographic characteristics and disability status at baseline. In stratified analyses, those not receiving formal care in the psychiatric diseases pattern (RRR 3.34; 95% CI 1.20‒9.32) and those not receiving formal or informal care in the 'cardiovascular diseases, anemia, dementia' pattern (RRR 2.99; 95% CI 1.20‒7.46; RRR 2.79; 95% CI 1.16‒6.71, respectively) had increased risks of institutionalization. CONCLUSIONS AND IMPLICATIONS: Older persons suffering from specific multimorbidity patterns have a higher risk of institutionalization, especially if they lack formal or informal care. Interventions aimed at preventing the clustering of diseases could reduce the associated burden on residential long-term care. Formal and informal care provision may be effective strategies in reducing the risk of institutionalization.

Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics.

INTRODUCTION: We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype. METHODS: A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses. RESULTS: People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity. DISCUSSION: Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.