A multidisciplinary approach to improve adherence to medical recommendations in older adults at hospital discharge: The APPROACH study protocol.

INTRODUCTION: Poor comprehension and medication adherence are common in older people, especially after hospitalizations, in case of changes or prescriptions of new therapeutic regimes. This randomized controlled trial aims to evaluate the effectiveness of an integrated approach in improving older individuals' adherence to medical recommendations after hospital discharge. METHODS: Data from an expected sample of 360 older inpatients (and their caregivers) will be collected. Medical recommendations' understanding will be tested before and after the routine explanation received by in-charge physicians. Participants will be randomized in the control (usual care) and intervention group. The intervention consists of educational training by a multidisciplinary team (occupational therapist, dietician, and physician, in consultation with a pharmacologist) at hospital discharge and, after hospital discharge, receiving a phone recall checking for therapy adherence and having the possibility to contact the study team for potential related concerns. After 7 days, medication adherence will be assessed through structured phone interviews comparing ongoing and prescribed medications and by administering the 4-item validated Morisky, Green, Levine scale and the Medication adherence report scale (MARS-5). At 30 and 90 days from discharge, data on medication adherence, falls, rehospitalizations, and vital status will be collected through phone interviews and hospital records. TRIAL REGISTRATION: Registration: NCT05719870 (clinicaltrial.gov). https://classic.clinicaltrials.gov/ct2/show/NCT05719870.

Sleep disorders during the COVID-19 pandemic: Results from the second phase of web-based EPICOVID19 study.

The COVID-19 pandemic has induced significant impairments, including sleep disturbances. The present study aimed to explore the impact of fear in relation to stress on sleep disorders among Italian adults and older participants in the second phase of the EPICOVID19 web-based survey (January-February 2021). Sleep disturbances during the pandemic were evaluated using the Jenkins Sleep Scale, perceived stress through the 10-item Perceived Stress Scale and fear of contagion and about economic and job situation with four ad hoc items. The strength of the pathways between stress, sleep disturbances and fear was explored using structural equation modelling, hypothesising that stress was related to sleep disturbances and that fear was associated with both stress and sleep problems. Out of 41,473 participants (74.7% women; mean age 49.7 ± 13.1 years), 8.1% reported sleep disturbances and were more frequently women, employed in a work category at risk of infection or unemployed, and showed higher deprivation scores. Considering an a priori hypotheses model defining sleep and stress scores as endogenous variables and fear as an exogenous variable, we found that fear was associated with sleep problems and stress, and stress was associated with sleep problems; almost half of the total impact of fear on sleep quality was mediated by stress. The impact of stress on sleep quality was more evident in the younger age group, among individuals with a lower socioeconomic status and healthcare workers. Fear related to COVID-19 seem to be associated with sleep disturbances directly and indirectly through stress.

Effects of PROtein enriched MEDiterranean Diet and EXercise on nutritional status and cognition in adults at risk of undernutrition and cognitive decline: the PROMED-EX Randomised Controlled Trial.

INTRODUCTION: Undernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade or more, providing a unique opportunity for early intervention to correct undernutrition and potentially prevent or delay cognitive impairment. The combined effects of diet and exercise on undernutrition have not yet been evaluated. The objective of this trial is to determine the effect of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline. METHODS: One hundred and five participants aged 60 years and over at risk of undernutrition and with subjective cognitive decline will be recruited to participate in a 6-month, single-blind, parallel-group randomised controlled trial. Participants will be block randomised into one of three groups: group 1-PROMED-EX (diet+exercise), group 2-PROMED (diet only) and group 3-standard care (control). The primary outcome is nutritional status measured using the Mini Nutritional Assessment. Secondary outcomes include cognitive function, nutritional intake, body composition, physical function and quality of life. Mechanistic pathways for potential diet and exercise-induced change in nutritional status and cognition will be explored by measuring inflammatory, metabolic, nutritional and metabolomic biomarkers. ETHICS AND DISSEMINATION: The study is approved by the UK Office for Research Ethics Committee (ref: 21/NW/0215). Written informed consent will be obtained from participants prior to recruitment. Research results will be disseminated to the public via meetings and media and the scientific community through conference presentations and publication in academic journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05166564).

Poverty and Influenza/Pneumococcus Vaccinations in Older People: Data from The Survey of Health, Ageing and Retirement in Europe (SHARE) Study.

Vaccine acceptance seems to be lower in poor people. The determinants of the lower vaccine coverage in poor people are not established. Therefore, we aimed to explore the association between poverty and influenza/pneumococcus vaccinations and the factors potentially associated with vaccination's coverage in poor people. The data of the Survey of Health, Ageing and Retirement in Europe (SHARE), an ongoing longitudinal, multi-disciplinary, and cross-national European study where used. Poverty was defined using information on income and household size. Among 47,370 participants initially included in the SHARE study, 12,442 were considered poor. In the multivariable logistic regression analysis, "Household size" was associated with a significantly lower vaccination probability, meanwhile "Age", "Years of education", "Regularly taking prescription drugs", and the level of income were significantly associated with higher probabilities of both influenza and pneumonia vaccinations. The "Number of illnesses/health conditions" was significantly associated with a higher probability of getting vaccination against influenza and against pneumococcus. In conclusion, among poor older people, several specific factors could be identified as barriers for the vaccinations against influenza or pneumococcus that are unique to this segment of the population, such as living with the family and having a job.

Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis.

Background: Breast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME. Methods: n = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher's and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan-Meier method. Results: The proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2- subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome. Conclusion: The TME dynamics of HR+/HER2- PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.

Ferric Carboxymaltose in Patients with Acute Decompensated Heart Failure and Iron Deficiency: A Real-Life Study.

Background: The correction of iron deficiency (ID) with ferric carboxymaltose (FCM) is a recommended intervention in heart failure (HF) with reduced ejection fraction. Our aim is to evaluate, in a real-life setting, the clinical significance of ID screening and FCM treatment in acute decompensated HF (ADHF). Methods: In a cohort of ADHF patients, the prevalence of ID and FCM administration were investigated. Among the 104 patients admitted for ADHF, in n = 90 (median age 84, 53.5% with preserved left ventricular ejection fraction-LVEF), a complete iron status evaluation was obtained. ID was detected in n = 73 (81.1%), 55 of whom were treated with in-hospital FCM. The target dose was reached in n = 13. Results: No significant differences were detected in terms of age, sex, comorbidities, or LVEF between the FCM-supplemented and -unsupplemented patients. During a median follow-up of 427 days (IQR 405-466) among the FCM-supplemented patients, only 14.5% received FCM after discharge; the mortality and rehospitalizations among FCM-supplemented and -unsupplemented patients were similar (p = ns). In a follow-up evaluation, ID was still present in 75.0% of the FCM-supplemented patients and in 69.2% of the unsupplemented patients (p = ns). Conclusions: In this real-life ADHF cohort, FCM was administered at lower-than-prescribed doses, thus having no impact on ID correction. The significance of our findings is that only achieving the target dose of FCM and pursuing outpatient treatment can correct ID and produce long-term clinical benefits.

Efficacy of COVID-19 control measures on post-vaccination outbreak in Italian Long Term Care Facilities: implications for policies.

Background: Numerous individual and organizational factors can influence the spread of SARS-CoV-2 infection in Long Term Care Facilities (LTCFs). A range of outbreak control measures are still implemented in most facilities involving administrations, staff, residents and their families. This study aims to evaluate which measure could influence the transmission of SARS-CoV-2 infection among residents during the period March 2021-June 2022. Methods: We enrolled 3,272 residents aged ≥60 years. The outbreak control measures adopted to prevent or manage the infection included entry regulations, contact-regulating procedures, and virological surveillance of residents and staff. The association between LTCFs' and participants' characteristics with new cases of COVID-19 infections was analyzed using multilevel logistic regression models. Results: In 33.8% of the facilities 261 cases of SARS-CoV-2 infection were reported. Among participant characteristics, gender and age were not associated with SARS-CoV-2 infection, while having received the vaccine booster dose was protective against infection [Odds Ratio (OR) = 0.34, 95% Confidence Interval (CI) 0.12-0.99, p = 0.048]. In addition, the implementation of protected areas for family visits was associated with a significant reduction of the probability of infections (OR = 0.18, 95% CI 0.03-0.98, p = 0.047). Overall, about 66% of the variability in the probability of SARS-CoV-2 infection during the observational period may be due to facility structure characteristics and 34% to the participant characteristics. Conclusions: These data showed that vaccination booster doses and family visit restriction-control are still needed to make the LTCFs safer against SARS-CoV-2 infection.

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.

Changes in sleep quality and sleep disturbances in the general population from before to during the COVID-19 lockdown: A systematic review and meta-analysis.

Introduction: This systematic review and meta-analysis aims to explore changes in sleep quality and sleep disturbances in the general population from before to during the COVID-19 lockdown. Methods: The protocol was registered in PROSPERO (CRD42021256378) and the PRISMA guidelines were followed. The major databases and gray literature were systematically searched from inception to 28/05/2021 to identify observational studies evaluating sleep changes in the general population during the lockdown with respect to the pre-lockdown period. A random effects meta-analysis was undertaken for studies reporting (a) the means of the Pittsburgh Sleep Quality Index (PSQI) global scores or the means of the sleep onset latency (SOL) times (minutes - min) before and during the lockdown, (b) the percentages of poor sleep quality before and during the lockdown, or (c) the percentages of changes in sleep quality. Subgroup analysis by risk of bias and measurement tool utilized was carried out. A narrative synthesis on sleep efficiency, sleep disturbances, insomnia and sleep medication consumption was also performed. Results: Sixty-three studies were included. A decline in sleep quality, reflected in a pooled increase in the PSQI global scores (standardized mean difference (SMD) = 0.26; 95% CI 0.17-0.34) and in SOL (SMD = 0.38 min; 95% CI 0.30-0.45) were found. The percentage of individuals with poor sleep quality increased during the lockdown (pooled relative risk 1.4; 95% CI 1.24-1.61). Moreover, 57.3% (95% CI 50.01-61.55) of the individuals reported a change in sleep quality; in 37.3% (95% CI 34.27-40.39) of these, it was a worsening. The studies included in the systematic review reported a decrease in sleep efficiency and an increase in sleep disturbances, insomnia, and in sleep medication consumption. Discussion: Timely interventions are warranted in view of the decline in sleep quality and the increase in sleep disturbances uncovered and their potentially negative impact on health. Further research and in particular longitudinal studies using validated instruments examining the long-term impact of the lockdown on sleep variables is needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256378, identifier CRD42021256378.

Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study.

BACKGROUND AND OBJECTIVES: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. METHODS: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. RESULTS: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. DISCUSSION: The use of trazodone was highly prevalent in functionally dependent and comorbid older adults admitted to LTCF or living at home. Clinical conditions associated with its prescription included depression as well as BPSD.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Somatically evoked cough responses help to identify patients with difficult-to-treat chronic cough: a six-month observational cohort study.

Background: Recently we identified in patients with chronic cough a sensory dysregulation via which the urge-to-cough (UTC) or coughing are evoked mechanically from "somatic points for cough" (SPCs) in the neck and upper trunk. We investigated the prevalence and the clinical relevance of SPCs in an unselected population of patients with chronic cough. Methods: From 2018 to 2021, symptoms of 317 consecutive patients with chronic cough (233 females) were collected on four visits (V1-V4) 2 months apart at the Cough Clinic of the University Hospital in Florence (I). Participants rated the disturbance caused by the cough (0-9 modified Borg Scale). We attempted to evoke coughing and/or UTC using mechanical actions in all participants who were subsequently categorised as responsive (somatic point for cough positive, SPC+) or unresponsive (SPC-) to these actions. An association was established between chronic cough and its commonest causes; treatments were administered accordingly. Findings: 169 patients were SPC+ and had a higher baseline cough score (p < 0.01). In most of the patients, the treatments reduced (p < 0.01) cough-associated symptoms. All patients reported a decrease (p < 0.01) in cough score at V2 (from 5.70 ± 1.4 to 3.43 ± 1.9 and from 5.01 ± 1.5 to 2.74 ± 1.7 for SPC+ and SPC- patients respectively). However, whilst in SPC- patients the cough score continued to decrease indicating virtually complete cough disappearance at V4 (0.97 ± 0.8), in SPC+ patients this variable remained close to V2 values during the entire follow-up. Interpretation: Our study suggests that the assessment of SPCs may identify patients whose cough is unresponsive and are eligible for specific treatments. Funding: This work was funded by an unrestricted grant from Merck (Italy).

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.

Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2.

BACKGROUND: Extensive research effort has been devoted to investigating the link between inflammation and PCa. However, this relationship remains unclear and controversial. The aim of our multi-center study was to investigate this association by histologically evaluating the distribution of PI and PCA in prostate biopsy cores from patients of eight referral centers in Italy. RESULTS: We evaluated 2220 cores from 197 patients; all the frustules were re-evaluated by dedicated pathologists retrospectively. Pathologists assigned IRANI scores and determined the positions of PIs; pathologists also re-evaluated the presence of PCa and relative ISUP grade. PCa was recorded in 749/2220 (33.7%). We divided this sample into a PCa PI group (634/749 cores [84.7%]) and a non-PCa + PI group (1157/1471 cores [78.7%]). We observed a statistically significant difference in the presence of inflammation among cores with cancer (p < 0.01). Moreover, periglandular inflammation was higher in the cores with neoplasia, while stromal inflammation was higher in cores without neoplasia (38.5% vs. 31.1% and 55.4% vs. 63.5% p < 0.01). CONCLUSIONS: In our experience, there is evidence of an association between PI and PCa at a tissue level. Further studies are needed to confirm our findings and to identify patients who might benefit from target therapies to prevent PCa occurrence and/or progression.

The role of nutrition and the Mediterranean diet on the trajectories of cognitive decline.

The worldwide burden of dementia is immense, and set to increase to unprecedented levels in the coming decades, due to population aging. In the absence of disease-modifying treatment, there is therefore a strong rationale to support the assumption that acting on modifiable risk factors, especially in midlife, is a good strategy for reducing the burden of dementia. Among these risk factors, nutrition is key, as it is fundamental to healthy aging, and has interrelated benefits on a number of organ systems, metabolic processes and health states that can all contribute to modifying the risk of dementia. In this paper, we review the methodological challenges of comparing studies of dietary interventions. We then discuss the effect of genetics and the environment on brain health, and review in particular the literature data on the effect of nutrition on cognition. We summarize the body of data reporting the largely beneficial effects of the Mediterranean diet on brain health, and the possible mechanisms that mediate these effects. Finally, we discuss future perspectives for further research in the field, notably the "gut-brain axis", thought to be a key mediator of the effect of nutrition on brain health.

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.

Frailty and the risk of infection-related hospitalizations in older age: Differences by sex.

OBJECTIVES: To investigate the extent to which frailty is associated with infection-related hospitalizations in older men and women, and to explore whether, among women, previous exposure to endogenous estrogens in terms of age at menopause and number of pregnancies modify such a relationship. STUDY DESIGN: The sample comprised 2784 participants in the Progetto Veneto Anziani aged ≥65 years. At baseline and after 4.4 years, frailty was identified according to the presence of three or more of the following: weakness, exhaustion, weight loss, low physical activity, and low walking speed. A passive follow-up on infection-related hospitalizations and mortality was performed for 10 years of observation through linkage with regional registers. MAIN OUTCOME MEASURES: The association between frailty and infection-related hospitalizations was assessed through mixed-effects Cox regressions. RESULTS: Frailty was significantly associated with a 78 % higher risk of infection-related hospitalization, with stronger results in men (hazard ratio = 2.32, 95 % confidence interval 1.63-3.30) than in women (hazard ratio = 1.54, 95 % confidence interval 1.18-2.02). Focusing on women, we found a possible modifying effect for the number of pregnancies but not menopausal age. Women who had experienced one or no pregnancy demonstrated a higher hazard of infection-related hospitalization as a function of frailty (hazard ratio = 3.00, 95 % confidence interval 1.58-5.71) than women who had experienced two or more pregnancies (hazard ratio = 1.68, 95 % confidence interval 1.18-2.39). CONCLUSION: Frailty in older age increases the risk of infection-related hospitalizations, especially in men. The "immunologic advantage" of the female sex in younger age seems to persist also after menopause as a function of the number of pregnancies a woman has experienced.

Early results of PRO-EPI: PROspective multicenter observational study on elective pelvic nodes irradiation in patients with intermediate/high/very high-risk non-metastatic prostate cancer submitted to radical, adjuvant, or salvage radiotherapy with or without concomitant androgen deprivation therapy.

Simple Summary: Although radiotherapy plays a fundamental role in the management of intermediate/high/very high-risk non-metastatic prostatic cancer (IHR-nmPca), there is still no consensus on the optimal treatment strategy in this setting. Remarkably, the role of elective nodal irradiation (ENI) is still highly controversial. The PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) was designed to provide "real life" data regarding the patterns of care for IHR-nmPca. Forty-three Italian Radiation Oncology centers participated in the PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) project, with 1029 patients enrolled. In this preliminary analysis, we longitudinally evaluated the impact of Elective Nodal Irradiation (ENI) and radiotherapy features on toxicity and quality of life (QoL). Six months follow-up data were available for 913 patients and 12 months data for 762 patients. Elective Nodal Irradiation was given to 506 patients (48.9%). Volumetric Intensity-Modulated Radiation Therapy (IMRT) was adopted in more than 77% of patients and Image-Guided Radiation Therapy (IGRT) in 84.4%. Androgen deprivation therapy (ADT) was administered to the majority of patients (68.3%), and it was associated to ENI in 408 cases (81.1%). Toxicity was mostly mild and reversible and IGRT resulted in a significant reduction of rectal toxicity, although a non-significant trend toward increased urinary toxicity was observed. No statistically significant differences in QoL and toxicity were seen in patients treated with or without ENI. The adoption of IGRT is widespread and increasing and could reduce treatment toxicity. ENI is not yet the standard treatment, but it is performed in a growing fraction of cases and not resulting into an increase in toxicity or in a deterioration of QoL. Further analyses are needed to clarify the long-term toxicity profile and the impact of ENI on survival.

Patient-Factors Influencing the 2-Year Trajectory of Mental and Physical Health in Prostate Cancer Patients.

This study aimed to examine the physical and mental Quality of Life (QoL) trajectories in prostate cancer (PCa) patients participating in the Pros-IT CNR study. QoL was assessed using the Physical (PCS) and Mental Component Score (MCS) of Short-Form Health Survey upon diagnosis and two years later. Growth mixture models were applied on 1158 patients and 3 trajectories over time were identified for MCS: 75% of patients had constantly high scores, 13% had permanently low scores and 12% starting with low scores had a recovery; the predictors that differentiated the trajectories were age, comorbidities, a family history of PCa, and the bowel, urinary and sexual functional scores at diagnosis. In the physical domain, 2 trajectories were defined: 85% of patients had constantly high scores, while 15% started with low scores and had a further slight decrease. Two years after diagnosis, the psychological and physical status was moderately compromised in more than 10% of PCa patients. For mental health, the trajectory analysis suggested that following the compromised patients at diagnosis until treatment could allow identification of those more vulnerable, for which a level 2 intervention with support from a non-oncology team supervised by a clinical psychologist could be of help.

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.