Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

OBJECTIVES: Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. METHODS: Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. RESULTS: Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. CONCLUSION: Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

Failure to reduce benzodiazepine prescriptions through the implementation of a psychological intervention for insomnia in an Italian mental health service.

PURPOSE: Despite the evidence of higher effectiveness of psychological interventions for insomnia compared to pharmacological ones, drug prescriptions for insomnia remain frequent. This study has assessed patterns of prescriptions of BZDs for insomnia before and after the delivery of a training in psychological interventions to professionals working in the services of a Department of Mental Health in northern Italy. METHODS: The intervention consisted in two training sessions about psychological interventions for insomnia delivered to professionals of the participating services. The prevalence of users with a prescription of BZDs for insomnia in an index period after the delivery of the training was compared to the prevalence in an index period before the training. RESULTS: Among 727 people assessed for BZDs prescription at pre-intervention, 306 (42.1%, 95% CI 0.39-0.46) had a prescription, and 344 (49.2%, 95% CI 0.45-0.53) had a prescription among 699 people assessed at post-intervention, corresponding to a significant odds ratio of 1.33 to be prescribed with BZDs in the second index period compared to the first one. Psychological interventions were offered to a small group of patients. CONCLUSION: Prescribing attitudes of BZDs for insomnia were not modified after the training and delivery of a psychological intervention in a mental healthcare outpatient setting. Prescribing habits should be addressed more directly in training, and professionals should be more aware of risks of BZDs assumption. The failure in changing drug prescriptions in this study should prompt more real-world studies of the application of evidence-based strategies, particularly in outpatient mental health settings.

Clinical relevance of clonal hematopoiesis in persons aged ≥80 years.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.

Correction: Technology-Assisted Cognitive Motor Dual-Task Rehabilitation in Chronic Age-Related Conditions: Systematic Review.

[This corrects the article DOI: 10.2196/44484.].

Technology-Assisted Cognitive Motor Dual-Task Rehabilitation in Chronic Age-Related Conditions: Systematic Review.

BACKGROUND: Cognitive-motor dual-task (CMDT) is defined as the parallel processing of motor (eg, gait) and cognitive (eg, executive functions) activities and is an essential ability in daily life. Older adults living with frailty, chronic conditions (eg, neurodegenerative diseases), or multimorbidity pay high costs during CMDT. This can have serious consequences on the health and safety of older adults with chronic age-related conditions. However, CMDT rehabilitation can provide useful and effective therapies for these patients, particularly if delivered through technological devices. OBJECTIVE: This review aims to describe the current technological applications, CMDT rehabilitative procedures, target populations, condition assessment, and efficacy and effectiveness of technology-assisted CMDT rehabilitation in chronic age-related conditions. METHODS: We performed this systematic review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, on 3 databases (Web of Science, Embase, and PubMed). Original articles that were published in English; involved older adults (>65 years) with ≥1 chronic condition and/or frailty; and tested, with a clinical trial, a technology-assisted CMDT rehabilitation against a control condition were included. Risk of bias (Cochrane tool) and the RITES (Rating of Included Trials on the Efficacy-Effectiveness Spectrum) tool were used to evaluate the included studies. RESULTS: A total of 1097 papers were screened, and 8 (0.73%) studies met the predefined inclusion criteria for this review. The target conditions for technology-assisted CMDT rehabilitation included Parkinson disease and dementia. However, little information regarding multimorbidity, chronicity, or frailty status is available. The primary outcomes included falls, balance, gait parameters, dual-task performance, and executive functions and attention. CMDT technology mainly consists of a motion-tracking system combined with virtual reality. CMDT rehabilitation involves different types of tasks (eg, obstacle negotiation and CMDT exercises). Compared with control conditions, CMDT training was found to be pleasant, safe, and effective particularly for dual-task performances, falls, gait, and cognition, and the effects were maintained at midterm follow-up. CONCLUSIONS: Despite further research being mandatory, technology-assisted CMDT rehabilitation is a promising method to enhance motor-cognitive functions in older adults with chronic conditions.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

Role of Sex and Age in Fatal Outcomes of COVID-19: Women and Older Centenarians Are More Resilient.

In the present paper, we have analysed the role of age and sex in the fatal outcome of COVID-19, as there are conflicting results in the literature. As such, we have answered three controversial questions regarding this aspect of the COVID-19 pandemic: (1) Have women been more resilient than men? (2) Did centenarians die less than the remaining older people? (3) Were older centenarians more resistant to SARS-CoV-2 than younger centenarians? The literature review demonstrated that: (1) it is women who are more resilient, in agreement with data showing that women live longer than men even during severe famines and epidemics; however, there are conflicting data regarding centenarian men; (2) centenarians overall did not die less than remaining older people, likely linked to their frailty; (3) in the first pandemic wave of 2020, centenarians > 101 years old (i.e., born before 1919), but not "younger centenarians", have been more resilient to COVID-19 and this may be related to the 1918 Spanish flu epidemic, although it is unclear what the mechanisms might be involved.

Impact of the post-COVID-19 condition on health care after the first disease wave in Lombardy.

BACKGROUND: Lombardy was affected in the early months of 2020 by the SARS-CoV-2 pandemic with very high morbidity and mortality. The post-COVID-19 condition and related public health burden are scarcely known. SETTING AND DESIGN: Using the regional population administrative database including all the 48,932 individuals who survived COVID-19 and became polymerase-chain-reaction negative for SARS-CoV-2 by 31 May 2020, incident mortality, rehospitalizations, attendances to hospital emergency room, and outpatient medical visits were evaluated over a mid-term period of 6 months in 20,521 individuals managed at home, 26,016 hospitalized in medical wards, and 1611 in intensive care units (ICUs). These data were also evaluated in the corresponding period of 2019, when the region was not yet affected by the pandemic. Other indicators and proxies of the health-care burden related to the post-COVID condition were also evaluated. MAIN RESULTS: In individuals previously admitted to the ICU and medical wards, rehospitalizations, attendances to hospital emergency rooms, and out-patient medical visits were much more frequent in the 6-month period after SARS-CoV-2 negativization than in the same prepandemic period. Performances of spirometry increased more than 50-fold, chest CT scans 32-fold in ICU-admitted cases and 5.5-fold in non-ICU cases, and electrocardiography 5.6-fold in ICU cases and twofold in non-ICU cases. Use of drugs and biochemical tests increased in all cases. CONCLUSIONS: These results provide a real-life picture of the post-COVID condition and of its effects on the increased consumption of health-care resources, considered proxies of comorbidities.

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study.

BACKGROUND: GLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) have shown to reduce the risk of major adverse cardiovascular events (MACE), death and worsening nephropathy when added to standard of care. However, these two dug classes differ in efficacy and safety. We compared the effectiveness and safety profile of GLP-1 RA and SGLT-2i in a large and unselected cohort of patients with type 2 diabetes resident in Lombardy from 2015 to 2020. METHODS: Using linkable administrative health databases, we included patients aged 50 years and older initiating GLP-1 RA or SGLT-2i. Clinical events were: death, hospital admission for myocardial infarction (MI), stroke, heart failure (HF), and renal disease as individual and composite outcomes (MACE-3: all cause-death, non-fatal MI, non-fatal stroke; MACE-4: MACE-3 plus unstable angina). Outcomes were evaluated separately in subjects with and without previous cardiovascular (CV) diseases. Treatments were compared using Cox proportional hazards regression model after Propensity Score Matching (PSM) in both intention-to-treat (ITT) and per protocol (PP) analyses. Serious adverse events were also evaluated. RESULTS: The analysis comprised 20,762 patients per cohort. The ITT analysis showed a significant risk reduction for non-fatal MI (HR 0.77; CI 95% 0.66-0.90), MACE-3 (HR 0.91; CI 95% 0.84-0.98), and MACE-4 (HR 0.92; CI 95% 0.86-0.99) in GLP-1RA compared with SGLT-2i users, while no difference was reported in the incidence of HF hospitalization and stroke between the two cohorts. Similar benefits were found in the subgroup of patients without previous CV diseases only. PP analysis largely confirmed the main results. The incidence of serious adverse events was low in both cohorts (< 1%). CONCLUSIONS: GLP-1RA showed to be equally safe and more effective than SGLT-2i in reducing the risk of MACE-3, MACE-4 and MI. This study adds to the growing body of real-world evidence addressing the specific clinical properties of GLP-1RA and SGLT-2i in everyday practice to tailor treatment to the individual patient.

Diabetes mellitus duration and mortality in patients hospitalized with acute myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) is associated with an increased mortality risk in patients hospitalized with acute myocardial infarction (AMI); however, no studies have investigated the impact of the duration of DM on in-hospital mortality. In this study, we evaluated in-hospital mortality in AMI patients according to DM status and its duration. METHODS: Using health administrative databases of Lombardy, DM patients≥50 years hospitalized with AMI from 2010 to 2019 were included in the analysis and were stratified according to the duration of DM: <5, 5-10, and > 10 years. The primary endpoint was mortality during AMI hospitalization and the secondary endpoint was 1-year mortality in comparison with No-DM patients. Logistic and Cox regressions analyses were used to estimate odds ratios (ORs, CI 95%) and hazard ratios (HRs, CI 95%) for the outcomes, according to DM status and duration and AMI type (STEMI and NSTEMI). RESULTS: Our study cohort comprised 29,566 and 109,247 DM and No-DM patients, respectively. Adjusted ORs and HRs showed a significantly higher risk of in-hospital mortality (OR 1.50, 95% CI 1.43-1.58) and 1-year mortality (HR 1.51, 95% CI 1.46-1.55) in DM patients in comparison with those without. These risks increased progressively with the duration of DM, with the highest risk observed in patients with DM duration ≥ 10 years (OR 1.59, 95% CI 1.50-1.69 for in-hospital mortality and HR 1.59, 95% CI 1.53-1.64 for 1-year mortality). These findings were similar in STEMI and in NSTEMI patients. CONCLUSIONS: Our study demonstrates that the duration of DM parallels mortality risk in patients hospitalized with AMI, highlighting that DM duration should be considered as an important early prognostic risk factor in patients with AMI.

Prognostic value of copeptin and mid-regional proadrenomedullin in COVID-19-hospitalized patients.

BACKGROUND: Biomarkers are used for diagnosis, risk stratification and medical decisions. Copeptin and mid-regional proadrenomedullin (MR-proADM) are markers of stress and endothelial function, respectively, which have been studied in pneumonia, sepsis and septic shock. This study aimed to assess whether copeptin and MR-proADM could predict coronavirus disease 2019 (COVID-19) in-hospital outcomes, that is multi-system complications, length of stay and mortality. METHODS: Copeptin and MR-proADM were assessed at admission in 116 patients hospitalized with COVID-19. Data were retrospectively extracted from an online database. The primary endpoint was in-hospital mortality. The secondary endpoints were in-hospital complications, the composite outcome 'death, or admission to intensive care unit, or in-hospital complications', and length of stay. The predictive power was expressed as area under the receiver operator characteristic curve (AUROC). RESULTS: Copeptin was increased in non-survivors (median 29.7 [interquartile range 13.0-106.2] pmol/L) compared to survivors (10.9 [5.9-25.3] pmol/L, p < 0.01). The AUROC for mortality was 0.71, with a hazard ratio of 3.67 (p < 0.01) for copeptin values > 25.3 pmol/L. MR-proADM differentiated survivors (0.8 [0.6-1.1] nmol/L) from non-survivors (1.5 [1.1-2.8] nmol/L, p < 0.001) and yielded a AUROC of 0.79 and a hazard ratio of 7.02 (p < 0.001) for MR-proADM values > 1.0 nmol/L. Copeptin and MR-proADM predicted sepsis (AUROC 0.95 and 0.96 respectively), acute kidney injury (0.87 and 0.90), the composite outcome (0.69 and 0.75) and length of stay (r = 0.42, p < 0.001, and r = 0.46, p < 0.001). CONCLUSIONS: Admission MR-proADM and copeptin may be implemented for early risk stratification in COVID-19-hospitalized patients to help identify those eligible for closer monitoring and care intensification.

Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy.

AIM: To compare the association of metformin use and coronavirus disease 2019 (COVID-19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy. METHODS: We used a COVID-19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus-2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19, and admission to an intensive care unit (ICU). RESULTS: In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91), and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI 0.67-0.81), and ICU admission (OR 0.77; 95% CI 0.63-0.95). CONCLUSIONS: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID-19 patients with diabetes.

Gait disorders in CKD patients: muscle wasting or cognitive impairment? A cross-sectional pilot study to investigate gait signatures in Stage 1-5 CKD patients.

BACKGROUND: Instrumental gait analysis in nephrology is widely neglected, although patients with chronic kidney disease (CKD) show brain changes due to cerebrovascular disease and metabolic disorders that can potentially influence gait quality. Our study assesses the association between CKD stages and gait parameters, to understand the prevalent status of brain related gait parameters (i.e. variability) and of performance related parameters (i.e. gait speed, stride length). We hypothesize that gait changes are detectable already in early stages of CKD. METHODS: Forty-five participants distributed in 5 CKD severity groups underwent an instrumental gait analysis via a triaxial accelerometer affixed to the lower trunk under single- and dual-task conditions. In addition to spatio-temporal parameters, variability and dual-task cost of gait were extracted. A battery of clinical assessments was conducted with the aim of helping to better explain the findings of the gait analysis. A correlation analysis was made to investigate a linear relation between gait parameters and CKD severity. RESULTS: Statistically significant correlations (Pearson correlation coefficient) with CKD severity were found for gait speed (p < 0.01, r = -0.55, 95% CI [-0.73;-0.30]), stride length ( p < 0.01, r = -0.40, 95% CI [-0.62;-0.12]), step length (p < 0.01, r = -0.41, 95% CI [-0.63;-0.13], coefficient of variance (CV) of step length (p = 0.01, r = 0.36, 95% CI [0.08;0.59]), gait regularity (p < 0.01, r = -0.38, 95% CI [-0.61;-0.10]), dual-task cost of gait speed (p < 0.01, r = 0.40, 95% CI [0.13;0.62]) and dual-task cost of stride time (p = 0.03, r = 0.32, 95% CI [0.03;0.57]). Adjustment for age and gender confirmed all results except for gait regularity. With increasing severity of renal failure, Handgrip strength, Time for the Expanded Timed Get Up and Go test, executive functions, haemoglobin, and haematocrit, worsen. CONCLUSIONS: The correlation of CKD severity with spatio-temporal parameters (performance indices mainly relatable to peripheral functionality) and with variability of gait (related to central factors) supported by the results of the clinical assessments, suggests that gait disturbance in CKD patients is not only due to metabolic factors that lead to muscle wasting, but also to brain changes that affect motor control. This suggests that the treatment of renal disease should include cognitive aspects in addition to metabolic and functional factors.

Lower risk of death and cardiovascular events in patients with diabetes initiating glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors: A real-world study in two Italian cohorts.

AIM: To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy. MATERIALS AND METHODS: An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks. RESULTS: After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. CONCLUSION: Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.

How palliative care professionals deal with predicting life expectancy at the end of life: predictors and accuracy.

PURPOSE: To assess the accuracy of hospice staff in predicting survival of subjects admitted to hospice, exploring the factors considered most helpful by the hospice staff to accurately predict survival. METHODS: Five physicians and 11 nurses were asked to predict survival at admission of 827 patients. Actual and predicted survival times were divided into ≤ 1 week, 2-3 weeks, 4-8 weeks, and ≥ 2 months and the accuracy of the estimates was calculated. The staff members were each asked to score 17 clinical variables that guided them in predicting survival and we analyzed how these variables impacted the accuracy. RESULTS: Physicians' and nurses' accuracy of survival of the patients was 46% and 40% respectively. Survival was underestimated in 20% and 12% and overestimated in 34% and 48% of subjects. Both physicians and nurses considered metastases, comorbidities, dyspnea, disability, tumor site, neurological symptoms, and confusion very important in predicting patients' survival with nurses assigning more importance to intestinal symptoms and pain too. All these factors, with the addition of cough and/or bronchial secretions, were associated with physicians' greater accuracy. In the multivariable models, intestinal symptoms and confusion continued to be associated with greater predictive accuracy. No factors appreciably raised nurses' accuracy. CONCLUSIONS: Some clinical symptoms rated as relevant by the hospice staff could be important for predicting survival. However, only intestinal symptoms and confusion significantly improved the accuracy of physicians' predictions, despite the high prevalence of overestimated survival.

Social isolation and loneliness as related to progression and reversion of frailty in the Survey of Health Aging Retirement in Europe (SHARE).

BACKGROUND: Frailty was shown to be associated with psychosocial risk factors, but there are few longitudinal data. METHODS: We used data from waves 5 and 6 of the Survey of Health Aging Retirement in Europe (SHARE) to study the contribution of loneliness and social isolation to transitions towards frailty defined according to Fried criteria in a sample of 27,468 individuals aged ≥60. RESULTS: At baseline, there were 13,069 (47.6%) robust individuals, 11,430 (41.6%) pre-frail and 2,969 (10.8%) frail. After 2 years, among robust subjects at baseline, 8,706 (61.8%) were still robust, 4,033 (30.8%) were pre-frail and 330 (2.6%) were frail. Among those who were pre-frail, 1,504 (13.2%) progressed to frail and 3,557 (31.1%) became robust. Among frail people, 182 (6.1%) reversed to robust and 1,271 (42.8%) to pre-frail. Average and high levels of loneliness and social isolation were significantly associated with the risk of robust people becoming frail and pre-frail (except robust with high loneliness to become frail), and of pre-frail people to become frail (except with average loneliness). Reversion to robustness was inversely associated with high levels of loneliness. CONCLUSION: Average levels of loneliness and social isolation should not be considered acceptable and should be actively addressed even in the absence of any health conditions through an available evidence-based intervention.

Comparison between drug therapy-based comorbidity indices and the Charlson Comorbidity Index for the detection of severe multimorbidity in older subjects.

BACKGROUND: To know burden disease of a patient is a key point for clinical practice and research, especially in the elderly. Charlson's Comorbidity Index (CCI) is the most widely used rating system, but when diagnoses are not available therapy-based comorbidity indices (TBCI) are an alternative. However, their performance is debated. This study compares the relations between Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), Chronic Disease Score (CDS), and severe multimorbidity, according to the CCI classification, in the elderly. METHODS: Logistic regression and Receiver Operating Characteristic (ROC) analysis were conducted on two samples from Italy: 2579 nursing home residents (Korian sample) and 7505 older adults admitted acutely to geriatric or internal medicine wards (REPOSI sample). RESULTS: The proportion of subjects with severe comorbidity rose with TBCI score increment, but the Area Under the Curve (AUC) for the CDS (Korian: 0.70, REPOSI: 0.79) and MCI (Korian: 0.69, REPOSI: 0.81) were definitely better than the DDCI (Korian: 0.66, REPOSI: 0.74). All TBCIs showed low Positive Predictive Values (maximum: 0.066 in REPOSI and 0.317 in Korian) for the detection of severe multimorbidity. CONCLUSION: CDS and MCI were better predictors of severe multimorbidity in older adults than DDCI, according to the CCI classification. A high CCI score was related to a high TBCI. However, the opposite is not necessarily true probably because of non-evidence-based prescriptions or physicians' prescribing attitudes. TBCIs did not appear selective for detecting of severe multimorbidity, though they could be used as a measure of disease burden, in the absence of other solutions.

Relation between anticholinergic burden and cognitive impairment: Results from the Monzino 80-plus population-based study.

PURPOSE: We examined data collected in the Monzino 80-plus study to assess the relations between cognitive performance and ACB scores according to the hypothesis that a higher anticholinergic burden is associated with reduced cognitive performance. METHODS: The Monzino 80-plus is an ongoing, prospective, door-to-door population-based study started in 2002 among all residents 80 years or older in eight municipalities of Varese province, Italy. To establish the relation between cognitive impairment and the anticholinergic drug burden we recorded the ACB score for each patient at baseline. The relations between ACB score and dementia or MMSE scores were also examined after exclusion of patients taking any antipsychotic. RESULTS: A sample of 2140 elderly people was eligible for analysis. A significant dose-effect relationship was observed between total ACB score and diagnosis of dementia in univariate and multivariate models. Patients in ACB class ≥4 had about 4.5 times the risk of diagnosis of dementia. A relation was also found between higher ACB scores and lower MMSE scores; patients who scored 4 or more had a mean of 6.4 points lower than those not taking anticholinergic drugs. The dose-effect relationship between ACB score and diagnosis of dementia was not maintained after exclusion of patients using antipsychotics, while the association between higher ACB scores and lower MMSE scores was still present, with patients in ACB class ≥4 having a mean score about 4.4 lower. CONCLUSIONS: There are clear relations between anticholinergic load and reduced cognitive performance, while the association with dementia remains uncertain. For primary care and geriatric clinicians, an ACB score ≥ 4 can be considered the cut-off to identify high-risk populations who may benefit from the evaluation of anticholinergic burden with the ACB scale.

Association of renal function with cognition, functional ability and mood in the oldest-old: The 'Health and Anemia study'.

AIM: In this study, the relationship between kidney function, cognitive performance, functional abilities and mood was investigated in a community-dwelling Italian oldest-old population. METHODS: Serum creatinine was used to calculate estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula, for 415 oldest-old without dementia participating in the 'Health and Anemia' study, a prospective, observational cohort study. The cross-sectional associations of kidney function with cognitive performance on several neuropsychological tests, basic and instrumental functional abilities and mood were analyzed using univariate and multivariable linear regression models. RESULTS: Cognitive performance and functional ability significantly worsened with decreasing kidney function. After adjusting for age, sex, education, comorbidity index of the Cumulative Illness Rating Scale (CIRS), body mass index, bone fracture and serum ferritin levels the associations of eGFR categories with basic and instrumental functional abilities continued to be statistically significant whereas that with global cognitive functions did not. No significant independent association was found between renal function and mood. CONCLUSIONS: Oldest-old with reduced kidney function showed greater basic and instrumental functional disabilities, while cognitive function, although decreased with decreasing eGFR, was no longer significantly associated with eGFR categories after adjusting for confounders.

Incidence of dementia in the oldest-old and its relationship with age: The Monzino 80-plus population-based study.

INTRODUCTION: Relationship between age and dementia at extreme old ages is still an open question, yet population-based studies in this high-risk age segment are rare. METHODS: The Monzino 80-plus is a population-based study among residents 80 years and older in the Varese province, Italy. Of 1371 eligible individuals, 1294 (94.4%), of whom 64 are centenarians, were included in the incidence study. RESULTS: Since 2002, 584 new cases of all-cause dementia were identified over 15 years. The overall incidence rate was 7.9 per 100 person-years. Dementia risk rose with age (IRR: 1.06), with the cubic model providing the best fit (R2  = 0.91-0.96). Cumulative incidences of dementia unadjusted and adjusted for competing mortality risk progressively diverged with age. CONCLUSION: Dementia incidence also keeps rising in nonagenarians and centenarians. Slowing down in growing risk of developing dementia with age is mainly attributable to increasing competing risk of death and resulting selective survival of individuals at lower risk of dementia.