Long-term beneficial impact of the randomised trial 'Train the Brain', a motor/cognitive intervention in mild cognitive impairment people: effects at the 14-month follow-up.

No treatment options are currently available to counteract cognitive deficits and/or delay progression towards dementia in older people with mild cognitive impairment (MCI). The 'Train the Brain' programme is a combined motor and cognitive intervention previously shown to markedly improve cognitive functions in MCI individuals compared to non-trained MCI controls, as assessed at the end of the 7-month intervention. Here, we extended the previous analyses to include the long-term effects of the intervention and performed a data disaggregation by gender, education and age of the enrolled participants. We report that the beneficial impact on cognitive functions was preserved at the 14-month follow-up, with greater effects in low-educated compared to high-educated individuals, and in women than in men.

Frailty Prevalence, Incidence, and Association with Incident Disability in the Italian Longitudinal Study on Aging.

INTRODUCTION: Data on frailty frequency are heterogeneous and mostly based on cross-sectional studies. Little is known about frailty development and progression over time. Our aim was to conduct a systematic analysis of frailty prevalence and incidence in a large cohort of older adults and to evaluate the association with incident disability, in order to tackle the current paucity and fragmentation of longitudinal data on frailty. METHODS: As secondary analysis of the Italian Longitudinal Study on Aging (ILSA) population-based cohort (n = 5,632, 65-84), frailty status was operationalized according to Fried criteria (n = 2,457). Weighted prevalence and incidence rates were calculated at each ILSA wave (T0 1992-1993, T1 1995-1996, T2 2000-2001). The association with incident disability in Activities of Daily Living (ADL) or Instrumental Activities of Daily Living (IADL) was investigated through Cox proportional hazard models, controlling for possible confounders. RESULTS: Prevalence of frailty and pre-frailty at baseline (mean age 71.6 years; women 58.9%) were 4.0% (95% confidence interval [CI]: 3.4-4.6) and 44.6% (95% CI: 43.1-46.1), respectively. Incidence rates per 1,000 person-years for the T0-T1 interval were 7.3 (95% CI: 5.2-9.3) for frailty and 83.7 (95% CI: 73.6-93.8) for pre-frailty. Prevalence and incidence of frailty, and to a lesser degree of pre-frailty, were overall higher for women and increased with age, yet no increasing trend with advancing age was detected for pre-frailty incidence. Frailty incidence rates were significantly higher among pre-frail than non-frail individuals at follow-up entry. After full adjustment, being frail markedly increased the risk of incident disability in ADL (hazard ratio [HR] 3.58, 95% CI: 1.97-6.52) and IADL (HR 2.56, 95% CI: 1.58-4.16) over a 4-year period. DISCUSSION/CONCLUSION: According to our findings, frailty is common among older people and is a strong and independent predictor of disability. Further research on factors and characteristics related to frailty progression, and especially remission, over time is crucial to calibrate effective public health preventive measures.

Hospital length of stay and 30-day readmissions in older people: their association in a 20-year cohort study in Italy.

BACKGROUND: There are conflicting data on whether hospital length of stay (LOS) reduction affects readmission rates in older adults. We explored 20-year trends of hospital LOS and 30-day rehospitalizations in a cohort of Italian older people, and investigated their association. METHODS: Participants in the Pro.V.A. project (n = 3099) were followed-up from 1996 to 2018. LOS and 30-day rehospitalizations, i.e. new hospitalizations within 30 days from a previous discharge, were obtained from personal interviews and regional registers. Rehospitalizations in the 6 months before death were also assessed. Linear regressions evaluated the associations between LOS and the frequency of 30-day rehospitalizations, adjusting for the mean age of the cohort within each year. RESULTS: Over 20 years, 2320 (74.9%) participants were hospitalized. Mean LOS gradually decreased from 17.3 days in 1996 to 11.3 days in 2018, while 30-day rehospitalization rates increased from 6.6% in 1996 to 13.6% in 2018. LOS was inversely associated with 30-day rehospitalizations frequency over time (ß = -2.33, p = 0.01), similarly in men and women. A total of 1506 individuals was hospitalized within 6 months before death. The frequency of 30-day readmissions at the end of life increased from 1.4% in 1997 to 8.3% in 2017 and was associated with mean LOS (ß = -1.17, p = 0.03). CONCLUSIONS: The gradual LOS reduction observed in the latter decades is associated with higher 30-day readmission rates in older patients in Italy. This suggests that a careful pre-discharge assessment is warranted in older people, and that community healthcare services should be improved to reduce the risk of readmission.

Risk of progression to diabetes and mortality in older people with prediabetes: The English longitudinal study on ageing.

AIMS: Prediabetes is used to identify people at increased risk for diabetes. However, the importance of prediabetes in older populations is still poorly explored. Therefore, we aimed to investigate the prevalence of prediabetes, based on either glycated haemoglobin (HbA1c) levels or fasting glucose (FG) levels, or both and the progression of prediabetes to diabetes or to mortality in older participants of the English Longitudinal Study on Ageing. MATERIALS AND METHODS: Prediabetes was categorized based on HbA1c levels (5.7%-6.4%) and/or FG levels (5.6-7.0 mmol/L). Information regarding mortality and incident diabetes were recorded during follow-up period of 10 years. RESULTS: In 2027 participants (mean age: 70.6 years, 55.2% females), the prevalence of prediabetes ranged between 5.9% and 31.1%. Over 8 years of follow-up, 189 participants (5.4% of the initial population) developed diabetes and 606 (17.4%) died. Among 1,403 people with HbA1c at the baseline <5.7%, 33 developed diabetes and 138 died; in contrast, among 479 participants with a diagnosis of prediabetes using a value of HbA1c between 5.7% and 6.4%, 62 developed diabetes and 56 died. Similarly, among 1,657 people with normal values of FG at baseline 60 had a diagnosis of diabetes during follow-up and 163 died, compared to 225 with FG between 5.6 mmol/L and 7.0 mmol/L in which 35 developed diabetes and 31 died. CONCLUSION: The prevalence of prediabetes in older adults is high, but the progression from prediabetes to diabetes is uncommon, whereas the regression to normoglycemia or the progression to death was more frequent.

Multidimensional frailty and quality of life: data from the English Longitudinal Study of Ageing.

PURPOSE: Frailty has been found to be associated with poor quality of life (QoL) in older people, but data available are limited to cross-sectional studies. We therefore aimed to assess the association between multidimensional frailty, determined by Multidimensional Prognostic Index (MPI), with mortality and good QoL expectancy (GQoLE) in a large representative sample of older adults, over 10 years of follow-up. METHODS: In the English Longitudinal Study of Ageing, using the data from 2004-2005 and 2014-2015, MPI was calculated using a weighted score of domains of comprehensive geriatric assessment, i.e., number of difficulties in activities of daily living (ADL) and instrumental ADL, depressive symptoms, number of medical conditions, body mass index, physical activity level, and social aspects. Mortality was assessed using administrative data, GQoLE indicators were used for longitudinal changes in QoL. RESULTS: 6244 Participants (mean age 71.8 years, 44.5% males) were followed up for 10 years. After adjusting for potential confounders, compared to people in the MPI low-risk group, people in the moderate (hazard ratio, HR = 4.27; 95% confidence interval, CI 3.55-5.14) and severe-risk group (HR = 10.3; 95% CI 7.88-13.5) experienced a significantly higher mortality rate. During the follow-up period, people in the moderate and severe-risk groups reported lower GQoLE values than their counterparts, independently from age and gender. CONCLUSIONS: Multidimensional frailty was associated with a higher risk of mortality and significantly lower GQoLE, suggesting that the multifactorial nature of frailty is associated not only with mortality, but also poor QoL.

Prevalence and impact of polypharmacy in older patients with type 2 diabetes.

BACKGROUND: Polypharmacy is a prevalent condition in older adults, especially those with multiple chronic diseases, and has been largely associated with adverse outcomes, including disability, hospitalizations, and death. AIMS: This systematic review focused on diabetes and aimed to investigate the prevalence and impact of polypharmacy in older adults affected by such disease. METHODS: Observational (either cross-sectional or longitudinal) or experimental studies investigating the frequency and impact of polypharmacy in older adults with diabetes were identified from scientific databases and grey literature until August 2021. The prevalence and the 95% Confidence Interval (95% CI) of polypharmacy in older people with diabetes were summarized by a random-effects meta-analysis. RESULTS: From a total of 1465 records, 9 were selected for the qualitative synthesis, and 8 for the quantitative synthesis. Most studies defined polypharmacy using a cut-off for the minimum number of medications ranging from 4 to 6 drugs/day. The pooled prevalence of polypharmacy in older people with diabetes was 64% (95% CI 45-80%). Considering studies that used the same definition of polypharmacy (i.e. ≥ 5 drugs/day), the pooled prevalence was 50% (95% CI 37-63%). The between-studies heterogeneity was high. Across the selected studies, polypharmacy seemed to negatively influence both diabetes-specific (poor glycemic control and risk of hypoglycemia) and health-related (risk of incident falls, syncope, hospitalization, and death) outcomes. CONCLUSION: This systematic review confirms the high prevalence of polypharmacy in older people with diabetes and its strong impact on several health-related outcomes, including mortality. These results strengthen the need to improve care strategies for management of these patients.

Clinical trial on the effects of oral magnesium supplementation in stable-phase COPD patients.

BACKGROUND AND AIMS: COPD is a common chronic condition in older age that impacts on daily activities and quality of life. Previous studies suggest that magnesium deficit in COPD patients affects bronco-obstruction, inflammation, and physical performance. We investigated whether oral magnesium supplementation in stable-phase COPD patients improves lung function, physical performance, and quality of life. METHODS: We conducted a double-blind randomized-controlled clinical study with 49 participants divided into two groups: one given 300 mg/day of magnesium citrate (n = 25) and the other one sachet/day of a placebo (n = 24). The following parameters were assessed at baseline and after 3 and 6 months: lung function (spirometry), physical performance (handgrip strength, lower limb strength, six-minute walk test), inflammation (e.g., C-reactive protein, CRP), disease-related symptoms, and quality of life (St George's Respiratory Questionnaire, EuroQoL-5D, the Modified British Medical Research Council Questionnaire). RESULTS: Linear mixed models revealed significantly lower CRP values in the intervention group than in the placebo group at the 6 month follow-up (ß = - 3.2, 95% CI - 6.0, - 0.4, p = 0.03). Moreover, the maximum work for flexion tended to increase in both groups between the 3 and the 6 month assessments, especially in the placebo group. No significant differences within and between groups over the study period were observed for the other parameters tested. CONCLUSIONS: Although the established minimum sample size was not reached, our results suggests that oral magnesium supplementation may have a potential anti-inflammatory role. On the other hand, it does not seem to substantially influence lung function, physical performance, and quality of life in COPD patients. TRIAL REGISTRATION: The study is registered in clinicaltrial.gov (Trial Registration: NCT02680769, 13 June 2016, retrospectively registered).

The prevalence of frailty and its associated factors in an Italian institutionalized older population: findings from the cross-sectional Alvise Cornaro Center Study.

BACKGROUND: While it is well established that frail older people have a higher risk of negative health outcomes, the prevalence of frailty and its associated factors in Italian older institutionalized population has never been investigated. AIMS: The aims of this study were to assess the prevalence of frailty and to identify its associated factors in an Italian residential care home population. METHODS: An observational cross-sectional study was designed to evaluate older people aged 70 or over of an Italian residential care home. A multidimensional assessment examining functional, geriatric, ophthalmic, and audiological domains was carried out to identify factors associated with frailty. Physical frailty was evaluated using Fried's criteria. RESULTS: Data analysis uncovered a 51.1% prevalence of pre-frailty and a 40.4% prevalence of frailty in the 94 eligible participants (64 females) whose data were complete. The multivariable analysis showed that a low education level (OR = 5.12, 95% CI 1.22-21.49), a low physical quality of life score (OR = 13.25, 95% CI 3.51-50.08), a low mental quality of life score (OR = 9.22, 95% CI 2.38-35.69), visual impairment (OR = 7.65, 95% CI 1.77-33.14), and hearing impairment (OR = 4.62, 95% CI 1.03-20.66) were independently associated with frailty. CONCLUSIONS: Frailty was found to be highly prevalent in the residential care home studied. Since frailty is a reversible condition, identifying the modifiable factors associated to it should be viewed as an important step in planning and implementing targeted, early prevention strategies.

The increased cortisol levels with preserved rhythmicity in aging and its relationship with dementia and metabolic syndrome.

BACKGROUND: In the aging process, the cumulative exposure to stress with increased cortisol levels is considered to be associated to the senescence itself and its related disorders. AIMS: To evaluate the role of cortisol in elderly subjects, with or without dementia, by the means of the AGICO study. METHODS: The AGICO study enrolled patients from ten Geriatric Units in Italy in 2012-2017 (Study Director Prof Paolo Falaschi, S. Andrea Hospital of Rome). Every subject received a comprehensive geriatric assessment (including the Mini-Mental State Examination, MMSE), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal). RESULTS: The MMSE was inversely related to the standardized diurnal and nocturnal urinary cortisol levels (p < 0.025 and p < 0.01, respectively) and the age was positively related (p < 0.01 and p < 0.001, respectively). The ratio between the standardized diurnal and nocturnal urinary cortisol levels was 1.50 ± 1.2 (mean ± standard deviation) and it was not modified by the age or dementia. The standardized diurnal and nocturnal urinary cortisol levels were significantly higher in patients with dementia (MMSE < 24) (p < 0.01). In the analysis of the subgroups with MetS, the highest concentrations of diurnal and nocturnal cortisol were found in patients with both dementia and MetS (p < 0.025 and p < 0.01, respectively). DISCUSSION: The AGICO study showed that the stress response significantly and progressively increases with age. CONCLUSION: The cortisol increase in aging is related to the presence of both dementia and metabolic syndrome.

Trajectories of cognitive and physical performance after accidental falls in nursing home residents: A prospective study.

This prospective study evaluated cognitive and physical trajectories of nursing home (NH) residents after fall occurrence and their predictors. In 167 residents aged ≥60, we considered the closest pre-fall assessment and up to the first three post-fall assessments of cognitive and physical functions performed through Mini-Mental State Examination (MMSE) and Tinetti tests. Mixture models identified three post-fall cognitive and physical trajectories: stability, slow decline, and rapid decline. At logistic regression, older age, fewer informal visits, and falls within one month from institutionalization increased the probability of experiencing a decline in MMSE and Tinetti scores. Worse pre-fall cognitive function increased the likelihood of cognitive and physical decline, while worse pre-fall Tinetti score negatively impacted only physical decline. In conclusion, the impact of falls on the cognitive and physical health of NH residents may be modulated by their pre-fall cognitive function and some modifiable factors, such as social interactions and physical function.

How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Mild polypharmacy and MCI progression in older adults: the mediation effect of drug-drug interactions.

BACKGROUND: Polypharmacy has been associated with worse cognitive performance, but its impact on mild cognitive impairment (MCI) progression to dementia has not been explored. AIMS: The aims of the study were to investigate the association between multidrug regimens and MCI progression, and the possible mediation of drug-drug interactions and drugs' anticholinergic effect in such association. METHODS: This work included 342 older adults with MCI, who were involved in an Italian multicenter population-based cohort study. Information on drugs taken was derived from general practitioners' records and data on drug-drug interactions and anticholinergic burden [evaluated through the Anticholinergic Cognitive Burden and the Anticholinergic Risk Scale (ARS)] were extracted. Multinomial logistic regressions assessed the associations between mild polypharmacy (≥ 3 drugs/day), drug-drug interactions, and anticholinergic burden with MCI changes after 1-year follow-up. Mediation analysis evaluated potential mediators of that relationship. RESULTS: Approximately, 50% of participants took ≥ 3 drugs/day. During the follow-up, 4.1% of MCI patients progressed to dementia. The odds of developing dementia was sixfold higher in those who took ≥ 3drugs/day (OR = 6.04, 95% CI 1.19-30.74), eightfold higher in those with ≥ 1 drug-drug interaction/s (OR = 8.45, 95% CI 1.70-41.91), and fivefold higher in those with ARS ≥ 1 (OR = 5.10, 95% CI 1.04-24.93). Drug-drug interactions mediated 70.4% of the association between medication number and MCI progression to dementia (p = 0.07). DISCUSSION: Our study suggests that even mild polypharmacy may increase the risk of MCI progression to dementia, probably due to the presence of drug-drug interactions, which often occur in multidrug regimens. CONCLUSIONS: Older people require careful management of pharmacological treatments, with special attention to drug-drug interactions and drug-related anticholinergic effects.

Effects of combined training on neuropsychiatric symptoms and quality of life in patients with cognitive decline.

BACKGROUND AND AIMS: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. METHODS: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer's Disease (QOL-AD) scale. RESULTS: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. CONCLUSIONS: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can 'live well' with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.

Rapid COVID-19 Screening Based on Self-Reported Symptoms: Psychometric Assessment and Validation of the EPICOVID19 Short Diagnostic Scale.

BACKGROUND: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. OBJECTIVE: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. METHODS: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. RESULTS: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). CONCLUSIONS: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.

Epidemiology of Cardiovascular Diseases in the Elderly.

This chapter focuses on the epidemiology of cardiovascular diseases in elderly adults who are 65 or older. Risk factors for morbidity and mortality, as well as variables associated with disability and physical and social functional decline in the elderly individuals are considered. Modifiable risk factors, such as life habits are differentiated from unmodifiable ones, such as age and sex. The chapter concentrates in particular on the impact of hypertension, dyslipidemia and diabetes on cardiovascular diseases and mortality, as well as the effect of cigarettes smoking, physical activity, obesity and isolation on cardiovascular diseases and quality of life. The results demonstrate that cardiovascular diseases are not necessarily a consequence of aging; instead, they are often linked to modifiable risk factors. We can conclude that specific, targeted prevention interventions should preferably be implemented when individuals are young, but they are also useful in the elderly not only to prolong life but also to improve their quality of life.

The demographic and clinical characteristics of an Italian population of adult outpatients with chronic cough.

BACKGROUND: Chronic cough is a major health problem worldwide and patients are best managed in specialised tertiary centres. Little information is available on the characteristics of chronic cough patients in several European countries, including Italy. AIMS: We report on the demographic, anthropometric and clinical features of a large Italian population of adult chronic cough outpatients (about 1200), who were referred to a specialised clinic in Florence, Italy, from 2008 to 2018. METHODS: Demographic, environmental, lifestyle and clinical information was collected at enrolment by means of a custom-designed electronic questionnaire that only allowed for uniform responses. A subjective measure of cough-related discomfort (cough score) was also obtained using a modified Borg Scale. A multivariable logistic regression model was defined to identify the patients' characteristics associated with the cough score. RESULTS: The characteristics of the examined population (n = 1204 outpatients) were strikingly similar to those described elsewhere. Female patients outnumbered the males [n = 847 females, (70.0%)]; both females and males displayed the same average cough score. The median age of outpatients was 61 (quartile 1 = 48; quartile 3 = 70) years; age and cough duration were unrelated to the cough score. Nasal obstruction, coughing during consultation, coughing during meals, throat clearing and the presence of respiratory abnormalities were correlated with the degree of discomfort caused by coughing. DISCUSSION: The features of chronic cough patients are similar worldwide. The process of cough reflex hypersensitisation may soothe sex-related perceptual differences, leading to similar levels of discomfort. CONCLUSIONS: There seem to be clinical indicators that help in assessing the level of cough-related discomfort.

The mutual association between dyspnea and depressive symptoms in older adults: a 4-year prospective study.

Objectives: dyspnea in daily living (DDL), night-time dyspnea (NTD) and depression are common symptoms in older people. However, how changes in dyspnea may influence and be influenced by modifications in depressive symptoms, so far has not been fully evaluated. We aimed to estimate the extent to which both DDL and NTD could be mutually associated to depressive symptoms in older adults with chronic conditions.Methods: this prospective study includes 2322 community-dwelling individuals aged ≥65 years enrolled in the Progetto Veneto Anziani (Pro.V.A.). At baseline and after 4.4 years, we evaluated the following parameters: DDL, assessed by the Medical Research Council dyspnea scale (MRC); self-reported NTD, assessed by personal interview; depressive symptoms, assessed using the Geriatric Depression Scale (GDS). The strength of the association between dyspnea and depression over the follow-up was evaluated through logistic regression and estimated by odds ratios and 95%Confidence Intervals (95%CI). Corrected risk ratios (RR) were then approximated from odds ratios.Results: GDS changes over the follow-up positively correlated with MRC changes (ß = 0.938). Individuals with baseline DDL or NTD and those with incident/worsening DDL showed higher risk of developing or worsening depressive symptoms compared with their counterparts (RR = 3.36 [95%CI 2.11-5.06] for incident depression in people with worsening DDL). Incident or persistent depression increased more than twice the risk of developing DDL and NTD (for incident depression RR = 2.33 [95%CI 1.85-2.83] for DDL, and RR = 2.01 [95%CI 1.27-3.11] for NTD).Conclusions: older people may benefit from a comprehensive evaluation of respiratory and psychological symptoms, which seem to be related to each other in advanced age.

PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer.

Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors (p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.

Parathormone, vitamin D and the risk of atrial fibrillation in older adults: A prospective study.

BACKGROUND & AIMS: Vitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults. METHODS AND RESULTS: Data come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression. Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4-15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3-24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9-32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27-2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28-3.42). CONCLUSION: The risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.

The instruments used by the Italian centres for cognitive disorders and dementia to diagnose mild cognitive impairment (MCI).

AIMS: The purpose of this study was to examine the tools used in Italy to diagnose mild cognitive impairment (MCI). METHODS: In collaboration with the Luigi Amaducci Research Consortium, the Italian Network of Alzheimer Evaluation Units prepared a questionnaire to describe how MCI is diagnosed in the Italian Centres for cognitive disorders and dementia (CCDD). RESULTS: Most of the ninety-two CCDDs participating in the survey were located in hospitals (54.7%); large percentages were coordinated by neurologists (50.8%) and geriatricians (44.6%). Almost all (98.5%) used the Mini Mental State Examination to diagnose MCI; the Clock Drawing Test was also frequently used (83.9%). Other neuropsychological, imaging and biomarker tests were utilized less frequently and a wide diversity in the instruments used was noted. CONCLUSIONS: According to the results, diagnoses of MCI are based on a multitude of instruments, with major differences in the clinical assessment of geriatricians and neurologists. Standardized testing protocols, validated instruments and cut-off points need to be identified and adopted by the CCDDs for assessing MCI.