Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism.

Blood vessel formation is an important initial step for bone formation during development as well as during remodelling and repair in the adult skeleton. This results in a heavily vascularized tissue where endothelial cells and skeletal cells are constantly in crosstalk to facilitate homeostasis, a process that is mediated by numerous environmental signals, including mechanical loading. Breakdown in this communication can lead to disease and/or poor fracture repair. Therefore, this study aimed to determine the role of mature bone cells in regulating angiogenesis, how this is influenced by a dynamic mechanical environment, and understand the mechanism by which this could occur. Herein, we demonstrate that both osteoblasts and osteocytes coordinate endothelial cell proliferation, migration, and blood vessel formation via a mechanically dependent paracrine mechanism. Moreover, we identified that this process is mediated via the secretion of extracellular vesicles (EVs), as isolated EVs from mechanically stimulated bone cells elicited the same response as seen with the full secretome, while the EV-depleted secretome did not elicit any effect. Despite mechanically activated bone cell-derived EVs (MA-EVs) driving a similar response to VEGF treatment, MA-EVs contain minimal quantities of this angiogenic factor. Lastly, a miRNA screen identified mechanoresponsive miRNAs packaged within MA-EVs which are linked with angiogenesis. Taken together, this study has highlighted an important mechanism in osteogenic-angiogenic coupling in bone and has identified the mechanically activated bone cell-derived EVs as a therapeutic to promote angiogenesis and potentially bone repair.

Life events and the onset of motor symptoms in Parkinson's disease.

BACKGROUND: Whether there may be any relationship between stressful or traumatic life events (LE) and the subsequent motor symptoms onset in Parkinson's disease (PD) is still controversial. OBJECTIVES: To explore whether a subjectively perceived as stressful or traumatic LE were more frequently present in a group of recent motor onset parkinsonian patients (Recent Onset Parkinsonism - ROP) compared with healthy controls (HC) and a group of patients already diagnosed as PD. METHODS: A consecutive series of 139 ROP patients, 138 matched PD patients and 138 HC were pooled through a validated LE exposure questionnaire evaluating the number of patients affected by LE and the amount of LE per group occurred in the last year, segregating by subjective severity in total and severe LE. RESULTS: There was no significant difference in the percentage of patients affected by total (p = 0.134) nor by severe (p = 0.133) LE within the 3 groups. No significant difference was observed in the number of total LE between ROP and HC (p = 0.063), ROP and PD (p = 0.688), nor in severe LE (ROP vs. HC, p = 0.637. ROP vs. PD, p = 0.500). CONCLUSIONS: During the year of parkinsonian motor symptoms onset, the number of ROP patients exposed to total or severe LE or the amount of total or severe LE suffered by ROP were not significantly different to the group of PD patients or HC. A casual relationship between LE and the onset of motor symptoms in parkinsonian patients may be suggested.

Impact of COVID-19 pandemic on eating styles: A population based-survey during the first lockdown in Italy.

Background: The Coronavirus disease (COVID-19) pandemic has had a strong impact on eating behavior. To maintain health and well-being, correct nutrition is essential, especially when the immune system is under pressure. Objective: The aim of this study was to evaluate the correlation between emotional aspects and the eating behavior of a group of people living in Sicily during the lockdown due to COVID-19. Methodology: We used a cross-sectional survey design with an anonymous online questionnaire, administered through technological means. Results: During the COVID-19 pandemic, 91 participants experienced high stress (PSS = 18.14 ± 4.1), and eating was associated with emotional behaviors (DEBQ EM = 41.74 ± 10.9). Stress correlated positively with the emotional and external aspects of eating behaviors. Conclusion: The present study showed that the COVID-19 lockdown caused high stress with a worsening in eating behaviors. The study participants had difficulty in adequately coping with some emotions and feelings, developing an 'addiction' to food.

Validation of an events exposure questionnaire for individuals living in major cities of Argentina.

Most of the validated 'events exposure' questionnaires are focused on lifetime burden and are hardly applicable to Argentina owing to its sociocultural and natural conditions, where corruption and economic crises have been hitting middle-class people's lives in a cyclic manner. This prompted us to develop a new questionnaire, validated in Argentina, to assess the occurrence of exposure to events and their severity over a limited period. Deductive (bibliographic search) and inductive (by a Delphi group) selection was used to create an initial group of 24 questions, which were condensed into a final 14-item questionnaire. After administration to 512 inhabitants of the metropolitan area of Buenos Aires and other major cities in Argentina, the questionnaire was shown to have an intraclass correlation coefficient of 0.996 and an internal consistency, measured by the omega coefficient, of 0.86. Because this study was conducted during the coronavirus disease 2019 (COVID-19) pandemic, an additional question on how this situation affected individuals was included. The time span used to measure event exposure was 1 year prior to the study. In the case of an affirmative event exposure, the responder selected the severity of the stress perception generated on a Likert-like scale, ranging from 0 (nothing) to 5 (severe). Fifty-eight per cent of the responders were women, and the mean age was 47.14 years (SD: 13.97). The average annual event incidence per person was 2.5 events (SD: 1.88). Thirty-two per cent (164/512) reported at least one 5-point event on the severity scale. Ten per cent (51/512) responded that the COVID-19 pandemic affected them in a different manner than events related to personal or family disease, or the death of a close family member or friend.

La mayoría de los cuestionarios validados de 'exposición a eventos' se centran en la carga durante la vida y son difícilmente aplicables a la Argentina debido a las diferentes condiciones socioculturales y naturales, donde la corrupción y la crisis económica han estado golpeando la vida de las personas de clase media de una manera cíclica. Esto nos impulsó a desarrollar un nuevo cuestionario, validado en Argentina para evaluar la ocurrencia de exposición a eventos y su severidad en un período de tiempo determinado. Se utilizó selección deductiva (búsqueda bibliográfica) e inductiva (por un grupo Delphi) para crear un grupo inicial de 24 preguntas, que se condensaron en un cuestionario final de 14 ítemes con un coeficiente de correlación intraclase de 0.996 y una consistencia interna medida por el coeficiente Omega de 0.86, luego de la administración a 512 habitantes del área metropolitana de Buenos Aires y otras ciudades importantes de Argentina. Teniendo en cuenta que este estudio se realizó durante la situación de pandemia de COVID-19, se incluyó una pregunta adicional sobre cómo esta situación afectó a las personas. El intervalo de tiempo utilizado para medir la exposición a eventos fue el último año. En caso de una exposición de evento afirmativa, el respondedor tenía que seleccionar la severidad de la percepción del estrés generado en una escala tipo Likert, que va de 0 (nada) a 5 (grave). Cincuenta y ocho por ciento de los que respondieron eran mujeres, y la edad promedio fue de 47,14 años (DE = 13,97). La incidencia anual promedio de 'eventos' por persona fue de 2.5 eventos (DE = 1.88). Treinta y dos por ciento (164/512) informaron al menos un evento de 5 puntos en la escala de severidad. Diez por ciento (51/512) respondió que la pandemia de COVID-19 los afectó de manera diferente que la relacionada con la enfermedad personal o familiar o la muerte de un familiar cercano o amigo.

Public health and clinical approach to proactive management of frailty in multidimensional arena.

Background: Demographic changes have forced communities and people themselves to reshape ageing concepts and approaches and try to develop actions towards active and healthy ageing. In this context, the European Commission launched different private-public partnerships to develop new solutions and answers on questions related to this topic. The European Innovation Partnership on Active and Healthy Ageing, including topic related action groups as well reference sites committed towards a common action to facilitate active and healthy ageing, has contributed key elements for interventions, scaled up best practices and evaluated impact of their action to drive innovation across many regions in Europe over the past years. Methods: This paper describes action taken by A3 action group in the European Innovation Partnership on Active and Healthy Ageing. This paper gives an overview of how the partnership combined the view on frailty coming from public health as well as the clinical management. Results: Within different European regions, to tackle frailty, EIPonAHA partners have conceptualized functional decline and frailty, making use of good practice models working well on community programs. The A3 Group of EIPonAHA has worked alongside a process of innovation, targeting all ageing citizens with the clear goal of involving communities in the preventive approach. Conclusion: Engagement needs of older people with a focus on functionally rather than disease management as primary objective is considered as an overarching concept, also embracing adherence, compliance, empowerment, health literacy, shared decision-making, and activation. Furthermore, training of staff working with ageing people across all sectors needs to be implemented and evaluated in future studies.

The Validity of the SUNFRAIL Tool: A Cross-Sectional Study among Dutch Community-Dwelling Older People.

BACKGROUND: Early detection of frail older people is important. Timely intervention may allow health care professionals to prevent or delay the occurrence of adverse outcomes such as disability, increases in health care utilization, and premature death. OBJECTIVES: We assessed the construct and criterion validity of the SUNFRAIL tool, a questionnaire for measuring frailty among older people. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study was carried out in a sample of Dutch citizens. A total of 195 community-dwelling persons aged 71 years and older completed the questionnaire. MEASUREMENTS: Construct validity was examined by determining the correlation between the SUNFRAIL tool and the Tilburg Frailty Indicator (TFI). Criterion validity for the SUNFRAIL tool was determined by establishing the correlations with chronic diseases and adverse outcomes of frailty (disability, falls, indicators of health care utilization). Disability was measured using the Groningen Activity Restriction Scale. Participants also answered questions regarding falls and health care utilization. RESULTS: The construct validity of this tool was good and showed significant correlations with the TFI. The correlation between SUNFRAIL total and TFI total was 0.624. The criterion validity of the SUNFRAIL tool was good for chronic diseases and good-to-excellent for adverse outcomes disability, receiving nursing care, and falls. The area under the curve for these outcomes was 0.840 (95% CI 0.781-0.899), 0.782 (95% CI 0.696-0.868), and 0.769 (95% CI 0.686-0.859), respectively. CONCLUSIONS: The results of our study suggest that the SUNFRAIL tool is a valid instrument for assessing frailty in community-dwelling older people. It is an attractive instrument for use in practice because it takes little time for health care professionals and older people to complete the questionnaire, and it expresses the integral functioning of human beings.

Behavioral and hormonal effects of prolonged Sildenafil treatment in a mouse model of chronic social stress.

Chronic social defeat can inhibit the reproductive system of subordinate males and causes behavioral deficits. Sildenafil treatment increases mice testosterone levels through its effects on Leydig cells of mice and it has been found to work as an antidepressant drug both in humans and in animal models. Since previous findings showed that sildenafil can counteract the inhibitory effects of chronic social defeat on agonistic, reproductive and anxiety-like behaviors of subordinate male mice, we investigated whether these behavioral outcomes can be explained by Sildenafil stimulation of testosterone. CD1 mice underwent an intruder-resident paradigm. After the fifth day of test, subordinate mice were injected with either a 10 mg/kg Sildenafil or a saline solution for 4 weeks. The results of the present study showed that Sildenafil treatment increased counterattacking behaviors and sexual motivation of subordinate males in addition to limiting the increase in body weight often observed in subordinate mice following chronic psychosocial stress. Moreover, sildenafil treated mice showed a pattern of behaviors reflecting lower anxiety. In agreement with previous studies, Sildenafil also increased testosterone levels. These data demonstrate that sildenafil can counteract the effects of chronic stress, possibly through its stimulatory effects on Leydig cells. These data demonstrate that sildenafil might counteract the effects of chronic psychosocial stress through centrally and peripherally mediated mechanisms.

A Novel Tool for the Early Identification of Frailty in Elderly People: The Application in Primary Care Settings.

BACKGROUND: Frailty is a pre-disability condition in older persons providing a challenge to Health-Care Systems. Systematic reviews highlight the absence of a gold-standard for its identification. However, an approach based on initial screening by the General Practitioner (GP) seems particularly useful. On these premises, a 9-item Sunfrail Checklist (SC), was developed by a multidisciplinary group, in the context of European Sunfrail Project, and tested in the Community. OBJECTIVES: - to measure the concordance between the judgments of frailty (criterion-validity): the one formulated by the GP, using the SC, and the one subsequently expressed by a Comprehensive Geriatric Assessment Team (CGA-Team); - to determine the construct-validity through the correspondence between some checklist items related to the 3 domains (physical, cognitive and social) and the three tools used by the CGA-Team; - to measure the instrument's performance in terms of positive predictive value (PPV) and negative predictive value (NPV). DESIGN: Cross-sectional study, with a final sample-size of 95 subjects. SETTING: Two Community-Health Centers of Parma, Italy. PARTICIPANTS: Subjects aged 75 years old or more, with no disability and living in the community. MEASUREMENTS: We compared the screening capacity of the GP using the SC to that one of CGA-Team based on three tests: 4-meter Gait-Speed, Mini-Mental State Examination and Loneliness Scale. RESULTS: 95 subjects (51 women), with a mean age of 81±4 years were enrolled. According to GPs 34 subjects were frail; the CGA-Team expressed a frailty judgment on 26 subjects. The criterion-validity presented a Cohen's k of 0.353. Construct-validity was also low, with a maximum contingency-coefficient of 0.19. The analysis showed a PPV of 58.1% and a NPV equal to 84.6%. CONCLUSIONS: Our data showed a low agreement between the judgements of GP performed by SC and CGA-Team. However, the good NPV suggests the applicability of SC for screening activities in primary-care.

Augmentative and alternative communication improves quality of life in the early stages of amyotrophic lateral sclerosis.

This study aimed to evaluate the efficacy of low-tech augmentative and alternative communication (AAC) aids in improving quality of life (QoL) and mood disorders, as well as the psychosocial impact of assistive devices, in 10 patients affected by amyotrophic lateral sclerosis (ALS) in the early stage of the disease, when speech difficulties appear. The AACtraining (AAC-T) study lasted around six months and comprised two phases of three months each: AAC-intervention (AAC-I) followed by AAC-familiarization (AAC-F). All the patients were assessed at the beginning (T0) and at the end (T1) of AAC-I, as well as at the end of AAC-F (T2). During the AAC-I phase, we applied a three-phase AAC intervention model to evaluate intelligibility of language, participation patterns, communication needs and adaptation to the AAC tools. All the patients showed a gradual and significant improvement, especially in acceptance of the AAC aids, mood and QoL. Moreover, a reduction of caregiver burden was noted. Our study has demonstrated the utility of the AAC aids also in the early stages of the disease in patients with ALS presenting with dysarthria. In our opinion, AAC-T may act as a bridge between the initial and later phases of the disease, when patients need to use high-tech aids, including an eye-tracking communication device. In conclusion, in this study we highlighted how early AAC-T in patients with ALS may be a valuable tool to demonstrate how specific strategies and low-technology aids can improve QoL of these patients and their caregivers, also decreasing stress and depression.

Kawasaki disease triggered by parvovirus infection: an atypical case report of two siblings.

BACKGROUND: There are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients the idea of infective agents as trigger must be considered. CASE PRESENTATION: We describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis. The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions. Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%). He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister's history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome. CONCLUSIONS: We report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction. We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.

The predictive role of pelvic magnetic resonance in the follow up of spontaneous or induced puberty in turner syndrome.

Puberty is a critical age for patients with Turner syndrome (TS): infertility is reported to be linked to karyotype and spontaneous puberty and menarche occur in approximately 30% of patients, especially in mosaicism. However, it is not always predictable considering hormonal pattern and pelvic transabdominal ultrasound scan (US).The aim of the study is to compare the accuracy of Magnetic Resonance Imaging (MRI) and US to evaluate uterine and gonads volume, to visualize the presence of follicles and to predict spontaneous puberty and menarche in girls with TS. In a retrospective study, we evaluated 19 TS patients (age: 9-16 years), who underwent transabdominal pelvic US and pelvic MRI as required by parents. We correlated pelvic imaging with karyotype, hormonal data and pubertal outcome, and we compared US resolution to MRI.MRI revealed a higher accuracy in the study of uterus and ovaries, and permitted to measure ovaries not visualized by US. Ovarian volume, the presence of follicles and the occurrence of spontaneous puberty were not related to the karyotype; spontaneous puberty started in one patient with a karyotype 45,X and in two patients with mosaicism (45,X/46,XX; 47,XXX/45, X). Ovarian follicles were relieved by MRI in patients with a spontaneous menarche and the persistence of menstrual cycles correlated with an ovarian volume corresponding to Tanner stage 3-4. We stress the role of MRI in the follow-up of TS adolescents, guide in the choice of the timing of treatment.

The European Innovation Partnership on Active and Healthy Ageing Synergies: Protocol for a Prospective Observational Study to Measure the Impact of a Community-Based Program on Prevention and Mitigation of Frailty (ICP - PMF) in Community-Dwelling Older Adults.

Aim of this paper is to describe the protocol of the study "Impact of a Community-based Program on Prevention and Mitigation of Frailty in community-dwelling older adults" developed in the framework of the European Innovation Partnership on Active and Healthy Ageing. This proposal has been developed by the Partnership Action groups on frailty, fall prevention and polypharmacy in older. The proposal wants to assess the impact of community-based programs aimed to counteract three main outcomes related to frailty: hospitalization, institutionalization and death. Bringing together researchers from seven European countries, the proposal aims to achieve the critical mass and the geographical extension enough to provide information useful to all older European citizens. An observational study will be carried out to calculate the incidence of the different outcomes in relation to the various interventions that will be assessed; results will be compared with data coming from already established national, regional and local dataset using the observed/expected approach. The sample will be made up by at least 2000 citizens for each outcome. All the citizens will be assessed at the baseline with two multidimensional questionnaires: the RISC questionnaire and the Short Functional Geriatric Evaluation questionnaire. The outcomes will be assessed every six-twelve months.

Inappropriate Use of Proton Pump Inhibitors in Elderly Patients Discharged from Acute Care Hospitals.

BACKGROUND: Proton-pump inhibitors (PPI) are extensively prescribed in older patients. However, little information is available on factors associated to PPI prescribing patterns among older patients discharged from hospital. OBJECTIVE: To evaluate the appropriateness and clinical correlates of PPI prescription at discharge in a population of 1081 older patients discharged from acute care Italian hospitals. DESIGN: We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, a multicenter observational study. The appropriateness of PPI prescriptions was defined according to the Italian Medicines Agency (AIFA) rules. Correlates of overprescribing (i.e prescribing without recognized AIFA indications) and underprescribing (i.e. not prescribing despite the presence of recognized AIFA indications) were investigated by logistic regression analysis. RESULTS: Overprescribing was observed in 30% of patients receiving PPIs at discharge. Underprescribing was observed in 11% of patients not receiving PPIs at discharge. Overprescribing of PPIs at discharge was negatively associated with age (OR=0.88, 95%CI=0.85-0.91), depression (OR=0.58, 95%CI=0.35-0.96), use of aspirin (OR=0.03, 95%CI=0.02-0.06) and systemic corticosteroids (OR=0.02, 95%CI=0.01-0.04). The negative association with number of medications (OR=0.95, 95%CI=0.88-1.03) and overall comorbidities (OR=0.92, 95%CI=0.83-1.02) was nearly significant. Conversely, older age (OR=1.09, 95%CI=1.04-1.14), use of aspirin (OR=24.0, 95%CI=11.5-49.8) and systemic corticosteroids (OR=19.3, 95%CI=11.5-49.8) and overall comorbidities (OR=1.22, 95%CI=1.04-1.42) were independent correlates of underprescribing. CONCLUSION: Overprescribing of PPIs is more frequent in younger patients with lower burden of depression, whilst underprescribing is characterized by older age and greater burden of comorbidity and polypharmacy. Hospitalization should be considered as a clue to identify inappropriate use of PPIs and improve appropriateness of prescribing.

The Prognostic Value of High-sensitivity C-reactive Protein and Prealbumin for Short-term Mortality in Acutely Hospitalized Multimorbid Elderly Patients: A Prospective Cohort Study.

OBJECTIVES: To establish the predictive value on mortality after 2 months from hospital admission of two laboratory markers of nutritional and inflammatory status, high-sensitivity C-reactive protein (hs-CRP) and prealbumin, in a cohort of frail multimorbid elderly without terminal illness. DESIGN: Prospective cohort study. SETTING: Internal medicine ward of a large teaching hospital in Italy. PARTICIPANTS: 544 Caucasian patients with acute disease consecutively admitted from January to June 2013. 102 were excluded for being younger than 65 years old, having life expectancy <30 days or not having frailty syndrome. Further 42 patients were excluded for missing data or withdrawn at follow-up. Final analysis was performed on 400 subjects (179 M, 221 F, mean age 79±10). MEASUREMENTS: Serum prealbumin and hs-CRP were measured at admission. Death within 2 months from hospital admission was assessed through a telephonic interview with the caregiver for each patient discharged alive. Inhospital mortality was also recorded. Survival was calculated from date of admission to our unit. RESULTS: Mean prealbumin at admission was 17.3±7.7 mg/dl, while hs-CRP median was 24.2 mg/L (IQR 8.7 to 51.8). 108 patients (27%) died within two months from admission. In an age- and sex-adjusted analysis, log(hs-CRP) levels at admission, but not prealbumin, were independently associated with an increased risk for mortality (HR 1.40, 95% CI 1.18 to 1.66, p<0.001). After multiple adjustments for covariates, including comorbidity burden measured through Charlson score, log(hs-CRP) remained significantly associated with mortality (HR 1.38, 95% CI 1.08 to 1.76, p=0.01). A Receiver Operating Characteristic (ROC) curve was performed to test the predictive value of hs-CRP at admission on two-month mortality (AUC 0.68, 95% CI 0.63 to 0.72, p<0.001). Cut-off value was set at 38.4 mg/L. After dichotomization of hs-CRP values according to this cut-off, hs-CRP≥38.4 mg/L at admission proved to be a significant risk factor for mortality (HR 2.10, 95% CI 1.23 to 3.58, p=0.006). CONCLUSION: Serum hs-CRP, but not prealbumin, values at admission are predictors of short-term mortality at hospital admission in elderly multimorbid patients. Inflammation seems to affect prognosis more than malnutrition in this setting and may therefore guide clinicians' attitude towards therapeutic choices.

Integrating Information from FDG - and Amyloid PET for Detecting Different Types of Dementia in Older Persons. A Case-series Study.

A significant progress has been made in the understanding of the neurobiology of Alzheimer's disease. The post-mortem studies are the gold standard for a correct histopathological diagnosis, contributing to clarify the correlation with cognitive, behavioral and extra-cognitive domains. However, the relationship between pathological staging and clinical involvement remains challenging. Neuroimaging, including positron emission tomography (PET) and magnetic resonance, could help to bridge the gap by providing in vivo information about disease staging. In the last decade, advances in the sensitivity of neuroimaging techniques have been described, in order to accurately distinguish AD from other causes of dementia. Fluorodeoxyglucose-traced PET (FDG-PET) is able to measure cerebral metabolic rates of glucose, a proxy for neuronal activity, theoretically allowing detection of AD. Many studies have shown that this technique could be used in early AD, where reduced metabolic activity correlates with disease progression and predicts histopathological diagnosis. More recently, molecular imaging has made possible to detect brain deposition of histopathology-confirmed neuritic ß-amyloid plaques (Aß) using PET. Although Aß plaques are one of the defining pathological features of AD, elevated levels of Aß can be detected with this technique also in older individuals without dementia. This raises doubts on the utility of Aß PET to identify persons at high risk of developing AD. In the present case-series, we sought to combine metabolic information (from FDG-PET) and amyloid plaque load (from Aß PET) in order to correctly distinguish AD from other forms of dementia. By selecting patients with Aß PET + / FDG-PET + and Aß PET - / FDG-PET +, we propose an integrated algorithm of clinical and molecular imaging information to better define type of dementia in older persons.

The impact of drug interactions and polypharmacy on antimicrobial therapy in the elderly.

Infectious diseases are more prevalent in older people than in younger adults, and represent a major healthcare issue in older populations. Indeed, infections in the elderly are often associated with higher morbidity and mortality, and may present atypically. Additionally, older patients are generally treated with polypharmacy regimens, which increase the likelihood of drug-drug interactions when the prescription of an antimicrobial agent is needed. A progressive impairment in the functional reserve of multiple organs may affect either pharmacokinetics or pharmacodynamics during aging. Changes in body composition occurring with advancing age, reduced liver mass and perfusion, and reduced renal excretion may affect either pharmacokinetics or pharmacodynamics. These issues need to be taken into account when prescribing antimicrobial agents to older complex patients taking multiple drugs. Interventions aimed at improving the appropriateness and safety of antimicrobial prescriptions have been proposed. Educational interventions targeting physicians may improve antimicrobial prescriptions. Antimicrobial stewardship programmes have been found to reduce the length of hospital stay and improve safety in hospitalized patients, and their use in long-term care facilities is worth testing. Computerized prescription and decision support systems, as well as interventions aimed at improving antimicrobial agents dosage in relation to kidney function, may also help to reduce the burden of interactions and inherent costs.

Inappropriate prescribing in a large community-dwelling older population: a focus on prevalence and how it relates to patient and physician characteristics.

WHAT IS KNOWN AND OBJECTIVE: The prescription of potentially inappropriate medications (PIMs) for older adults is a well-known population health concern. Updated country-specific estimates of inappropriate prescribing in older adults using germane explicit criteria are needed to facilitate physician-tailored quality improvement strategies. Therefore, we sought to determine the prevalence of PIMs for older adults in Emilia-Romagna, Italy, using the updated Maio criteria. We also evaluated patient and general practitioner (GP) characteristics related to inappropriate prescribing. METHODS: Older adults (≥ 65) in 2012 were evaluated in a one-year retrospective study using administrative health care data. The 2011 Maio criteria includes 25 medications reimbursed by the Italian National Formulary, in the following categories in terms of severity: 16 medications that 'should always be avoided,' 3 that are 'rarely appropriate,' and 6 that have 'some indications although they are often misused.' To evaluate the extent of associations between patient and GP related characteristics, we used generalized estimating equations with an exchangeable covariance design to fit robust logistic regression models. RESULTS AND DISCUSSION: A total of 865,354 older adults were in the cohort and 28% had at least one PIM. Of the entire cohort, 8%, 10%, and 14% of individuals were prescribed at least one medication that 'should always be avoided,' is 'rarely appropriate,' and has 'some indications but are often misused,' respectively. Older patients (≥ 75) and females were more likely to be exposed to PIMs. 2,923 GPs were identified in the region, each having prescribed at least one PIM, of which older GPs (≥ 56), male GPs, and solo practice GPs were more likely to prescribe PIMs to their older patients. WHAT IS NEW AND CONCLUSION: The high prevalence of PIM exposure among older adults is a substantial issue in the region. Knowing how patient and GP characteristics relate to PIMs exposure may improve the design and targeting of initiatives for improving prescribing safety in this population.

Should post-mortem brain dissection be performed in Parkinson's disease with atypical dementia?

We describe a patient affected by PD with a rapid progression of cognitive decline. This case could suggest the coexistence of many neurodegenerative diseases, which is a common condition in older patients. We propose an hypothetical trajectory of the cognitive impairment usually associated with motor symptoms in the later phase of Parkinsonian patients. The trajectory is almost linear in classical Parkinson's disease dementia (PDD), while a constant acceleration of the cognitive decline with a subsequent change of the slope of the direction could suggest the coexistence of PD with other neurodegenerative disease. Finally, if the cognitive decline in PD is comparable to a "stepped" decline, vascular lesions could be the cause of the change of the slope. This case could suggest to request an autopsy in all cases of unexplained PDD, for better understanding the mixture of non-motor symptoms in PD.

Relationship between use of proton pump inhibitors and IGF system in older subjects.

OBJECTIVES: to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly. DESIGN: cross-sectional. SETTING: InCHIANTI study. PARTICIPANTS: 938 older subjects (536 women, 402 men, mean age 75.7±7.4 years). MEASUREMENTS: complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3). RESULTS: Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs. 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs. 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1-113.8] than non-users 110 [77.8-148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (ß±SE = -19.60±9.83, p=0.045). CONCLUSION: Use of PPIs was independently and negatively associated with IGF-1 levels.