A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

PURPOSE: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities. METHODS: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration. RESULTS: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration (P ≤ .05) compared with other active practices (n = 7). CONCLUSION: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients.

Integrating behavioral health & primary care for multiple chronic diseases: Clinical trial of a practice redesign toolkit.

Context: Most patients in need of behavioral health (BH) care are seen in primary care, which often has difficulty responding. Some practices integrate behavioral health care (IBH), with medical and BH providers at the same location, working as a team. However, it is difficult to achieve high levels of integration. Objective: Test the effectiveness of a practice intervention designed to increase BH integration. Study Design: Pragmatic, cluster-randomized controlled trial. Setting: 43 primary care practices with on-site BH services in 13 states. Population: 2,460 adults with multiple chronic medical and behavioral conditions. Intervention: 24-month practice change process including an online curriculum, a practice redesign and implementation workbook, remote quality improvement coaching services, and an online learning community. Outcomes: Primary outcomes were changes in the 8 Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain scores. Secondary outcomes were changes in medication adherence, self-reported healthcare utilization, time lost due to disability, cardiovascular capacity, patient centeredness, provider empathy, and several condition-specific measures. A sample of practice staff completed the Practice Integration Profile at each time point to estimate the degree of BH integration in that site. Practice-level case studies estimated the typical costs of implementing the intervention. Results: The intervention had no significant effect on any of the primary or secondary outcomes. Subgroup analyses showed no convincing patterns of effect in any populations. COVID-19 was apparently not a moderating influence of the effect of the intervention on outcomes. The intervention had a modest effect on the degree of practice integration, reaching statistical significance in the Workflow domain. The median cost of the intervention was $18,204 per practice. In post-hoc analysis, level of BH integration was associated with improved patient outcomes independent of the intervention, both at baseline and longitudinally. Conclusions: The specific intervention tested in this study was inexpensive, but had only a small impact on the degree of BH integration, and none on patient outcomes. However, practices that had more integration at baseline had better patient outcomes, independent of the intervention. Although this particular intervention was ineffective, IBH remains an attractive strategy for improving patient outcomes.

Further Experience with the Practice Integration Profile: A Measure of Behavioral Health and Primary Care Integration.

Valid measures of behavioral health integration have the potential to enable comparisons of various models of integration, contribute to the overall development of high-quality care, and evaluate outcomes that are strategically aligned with standard improvement efforts. The Practice Integration Profile has proven to discriminate among clinic types and integration efforts. We continued the validation of the measure's internal consistency, intra-rater consistency, and inter-rater consistency with a separate and larger sample from a broader array of practices. We found that the Practice Integration Profile demonstrated a high level of internal consistency, suggesting empirically sound measurement of independent attributes of integration, and high reliability over time. The Practice Integration Profile provides internally consistent and interpretable results and can serve as both a quality improvement and health services research tool.

Depression and cardiovascular risk-association among Beck Depression Inventory, PCSK9 levels and insulin resistance.

BACKGROUND: Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. RESULTS: In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. CONCLUSIONS: This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

A new dawn for managing dyslipidemias: The era of rna-based therapies.

The high occurrence of atherosclerotic cardiovascular disease (ASCVD) events is still a major public health issue. Although a major determinant of ASCVD event reduction is the absolute change of low-density lipoprotein-cholesterol (LDL-C), considerable residual risk remains and new therapeutic options are required, in particular, to address triglyceride-rich lipoproteins and lipoprotein(a) [Lp(a)]. In the era of Genome Wide Association Studies and Mendelian Randomization analyses aimed at increasing the understanding of the pathophysiology of ASCVD, RNA-based therapies may offer more effective treatment options. The advantage of oligonucleotide-based treatments is that drug candidates are targeted at highly specific regions of RNA that code for proteins that in turn regulate lipid and lipoprotein metabolism. For LDL-C lowering, the use of inclisiran - a silencing RNA that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis - has the advantage that a single s.c. injection lowers LDL-C for up to 6 months. In familial hypercholesterolemia, the use of the antisense oligonucleotide (ASO) mipomersen, targeting apolipoprotein (apoB) to reduce LDL-C, has been a valuable therapeutic approach, despite unquestionable safety concerns. The availability of specific ASOs lowering Lp(a) levels will allow rigorous testing of the Lp(a) hypothesis; by dramatically reducing plasma triglyceride levels, Volanesorsen (APOC3) and angiopoietin-like 3 (ANGPTL3)-LRx will further clarify the causality of triglyceride-rich lipoproteins in ASCVD. The rapid progress to date heralds a new dawn in therapeutic lipidology, but outcome, safety and cost-effectiveness studies are required to establish the role of these new agents in clinical practice.

Aging process, adherence to Mediterranean diet and nutritional status in a large cohort of nonagenarians: Effects on endothelial progenitor cells.

BACKGROUND AND AIM: Adherence to the Mediterranean Diet (MD) has been associated with a longer and better life. The aim of this study was to examine the effects of adherence to the MD, and of nutritional habits on endothelial progenitor (EPCs) and circulating progenitor (CPCs) cells in a cohort of nonagenarians enrolled within the Mugello Study, an epidemiological study aimed at investigating both clinically relevant geriatric items and various health issues, including those related to nutritional status. METHODS AND RESULTS: Four hundred twenty-one nonagenarians (306 F, 115 M, mean age: 93.1 ± 3.2 years) were evaluated. Adherence to MD was assessed through the Mediterranean Diet Score. Elderly subjects who were in the fourth quartile of the Mediterranean diet score showed significantly higher EPCs than subjects grouped into the other three quartiles. After adjustment for confounders, elderly subjects who were in the highest quartile of adherence to the MD score reported to have EPCs' levels significantly higher than those who reported lower values of adherence to the MD. Furthermore, by analyzing different food categories, it was reported that daily consumption of olive oil and a higher consumption of fruit and vegetables showed higher CPCs CD34+ and EPCs CD34+/KDR+ than subjects with not daily or lower consumption. CONCLUSION: Our results support the hypothesis that the adherence to MD, as well as a daily consumption of olive oil and fruit and vegetables, characteristics of MD, may protect against the development of endothelial dysfunction through increasing EPCs and CPCs in older age.

Body composition and metabolic changes during a 520-day mission simulation to Mars.

PURPOSE: The "Mars-500 project" allowed to evaluate the changes in psychological/physiological adaptation over a prolonged confinement, in order to gather information for future missions. Here, we evaluated the impact of confinement and isolation on body composition, glucose metabolism/insulin resistance and adipokine levels. METHODS: The "Mars-500 project" consisted of 520 consecutive days of confinement from June 3, 2010 to Nov 4, 2011. The crew was composed of six male subjects (three Russians, two Europeans, and one Chinese) with a median age of 31 years (range 27-38 years). RESULTS: During the 520-day confinement, total body mass and BMI progressively decreased, reaching a significant difference at the end (417 days) of the observation period (- 9.2 and - 5.5%, respectively). Fat mass remained unchanged. A progressive and significant increase of fasting plasma glucose was observed between 249 and 417 days (+ 10/+ 17% vs baseline), with a further increase at the end of confinement (up to + 30%). Median plasma insulin showed a non-significant early increment (60 days; + 86%). Total adiponectin halved (- 47%) 60 days after hatch closure, remaining at this nadir (- 51%) level for a further 60 days. High molecular weight adiponectin remained significantly lower from 60 to 168 days. CONCLUSIONS: Based on these data, countermeasures may be envisioned to balance the potentially harmful effects of prolonged confinement, including a better exercise program, with accurate monitoring of (1) the individual activity and (2) the relationship between body composition and metabolic derangement.

Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. METHODS: Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. RESULTS: A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. CONCLUSIONS: In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

CO2 laser vaporization for the treatment of vaginal intraepithelial neoplasia: effectiveness and predictive factors for recurrence.

OBJECTIVE: To evaluate the outcome of vaginal intraepithelial neoplasia (VaIN) treatment with CO2 laser vaporization in terms of local recurrence and progression to vaginal carcinoma. Additionally, the authors investigated the predictive factors for first recurrence. MATERIALS AND METHODS: The medical records of all patients treated for VaIN with CO2 laser vaporization at Sant'Anna Hospital in Turin (1995-2012), were retrospectively reviewed. A univariate logistic model was applied to evaluate selected clinical features as predictive factors for recurrence. A multivariate logistic regression analysis was then carried out including significant risk factors after univariate analysis (p < 0.05). RESULTS: The analysis included 285 out of 302 patients. Seventy-one (25%) women relapsed; of these 24 VaIN 1 (22%), 37 VaIN 2 (27%), and ten VaIN 3 (26%). The median time to the first recurrence was 5.2 months (1.4-127.8) for VaIN 1, 6.6 months (1-85.2) for VaIN 2, and 3.6 months (1.2-62) for VaIN 3. Sixty-one out of 71 patients were retreated with CO2 laser vaporization. At the last follow-up visit, 273 (96%) women were free from VaIN. No patients progressed to vaginal carcinoma. The multivariate model showed a higher risk of VaIN recurrence in the case of previous hysterectomy (HR 3.3, 95% CI 1.7-6.3, p < 0.001) and concomitant H-SIL on the Pap smear (HR 1.9, 95% CI 1.2-3.1, p = 0.008). CONCLUSION: CO2 laser vaporization is an effective low impact treatment for VaIN. Despite this, VaIN recur, in particular in cases of previous hysterectomy and concomitant H-SIL on the Pap smear. An intensive follow-up is proposed for women with a high risk of VaIN relapse.

Extracellular vesicles in cardiomyopathies: A narrative review.

Extracellular vesicles (EVs) are membrane-bound particles released by all cells under physiological and pathological conditions. EVs constitute a potential tool to unravel cell-specific pathophysiological mechanisms at the root of disease states and retain the potential to act as biomarkers for cardiac diseases. By being able to carry bioactive cargo (such as proteins and miRNAs), EVs harness great potential as accessible "liquid biopsies", given their ability to reflect the state of their cell of origin. Cardiomyopathies encompass a variety of myocardial disorders associated with mechanical, functional and/or electric dysfunction. These diseases exhibit different phenotypes, including inappropriate ventricular hypertrophy, dilatation, scarring, fibro-fatty replacement, dysfunction, and may stem from multiple aetiologies, most often genetic. Thus, the aims of this narrative review are to summarize the current knowledge on EVs and cardiomyopathies (e.g., hypertrophic, dilated and arrhythmogenic), to elucidate the potential role of EVs in the paracrine cell-to-cell communication among cardiac tissue compartments, in aiding the diagnosis of the diverse subtypes of cardiomyopathies in a minimally invasive manner, and finally to address whether certain molecular and phenotypical characteristics of EVs may correlate with cardiomyopathy disease phenotype and severity.

Enhancing walking performance with a bilateral hip exoskeleton assistance in individuals with above-knee amputation.

Transfemoral amputation is a debilitating condition that leads to long-term mobility restriction and secondary disorders that negatively affect the quality of life of millions of individuals worldwide. Currently available prostheses are not able to restore energetically efficient and functional gait, thus, recently, the alternative strategy to inject energy at the residual hip has been proposed to compensate for the lack of energy of the missing leg. Here, we show that a portable and powered hip exoskeleton assisting both the residual and intact limb induced a reduction of walking energy expenditure in four individuals with above-knee amputation. The reduction of the energy expenditure, quantified using the Physiological Cost Index, was in the range [-10, -17] % for all study participants compared to walking without assistance, and between [-2, -24] % in three out of four study participants compared to walking without the device. Additionally, all study participants were able to walk comfortably and confidently with the hip exoskeleton overground at both their self-selected comfortable and fast speed without any observable alterations in gait stability. The study findings confirm that injecting energy at the hip level is a promising approach for individuals with above-knee amputation. By reducing the energy expenditure of walking and facilitating gait, a hip exoskeleton may extend mobility and improve locomotor training of individuals with above-knee amputation, with several positive implications for their quality of life.

Higher uric acid levels are associated with better functional recovery in elderly patients receiving cardiac rehabilitation.

BACKGROUND AND AIMS: Whether uric acid (UA) serves as risk factor for cardiovascular diseases or as antioxidant defense has not yet been completely clarified. In this study we investigated the effects of UA on functional recovery in patients receiving cardiac rehabilitation. METHODS AND RESULTS: 306 patients, 209 men and 97 women, age range 25-87 years (mean 68 ± 11), performed the 6-min walk test (6mWT) before and after the rehabilitation, and the increase in walking distance was considered as the outcome measure of the study. Baseline UA serum levels ranged from 1.0 to 10.9 mg/dL (mean 5.2 ± 1.7). As there was a significant (p = 0.005) age*UA levels interaction, patients were divided into two subgroups, less then 65 years (n. 103, 68 men and 35 women, mean age 56 ± 9) and 65 years or more (n. 203, 141 men and 62 women, mean age 74 ± 5). After adjusting for relevant confounders, higher UA levels remained independent positive predictors of the increase in walking distance in older (p < 0.001) but not in younger patients (p = 0.807). CONCLUSIONS: Our findings show an independent association of higher UA levels with better functional recovery after cardiac rehabilitation selectively in elderly patients, suggesting that higher UA levels might reflect the decline in antioxidant defenses that occurs with advancing age. Future studies aimed at understanding the several contradictions concerning UA should, probably, address the issue within this perspective.

Practice integration profile revised: Improving item readability and completion.

INTRODUCTION: The Practice Integration Profile (PIP) is a reliable, valid, and broadly used measure of the integration of behavioral health (BH) into primary care. The PIP assesses operational and procedural elements that are grounded in the AHRQ Lexicon for Behavioral Health and Primary Care Integration. Prior analyses of PIP data and feedback from users suggested the measure was in need of revisions. This article describes the process used to improve readability, clarity, and pragmatic utility of the instrument. METHOD: Two rounds of structured cognitive interviews were conducted with clinicians in primary care settings. After each round, interview transcripts were coded by an analytic team using an iterative and consensus-driven process. Themes were identified based on codes. Themes and recommendations for revisions were reviewed and modified by committee. RESULTS: Based on feedback and a prior factor analysis of the PIP, revisions were undertaken to: (a) eliminate redundant or overlapping items; (b) clarify the meaning of items; (c) standardize the response categories, and (d) place items in the most appropriate domains. The resulting measure has 28 items in five domains. DISCUSSION: PIP 2.0 will need further examination to confirm its continuing use as a foundational tool for evaluating integrated care. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Synthesis and defect characterization of hybrid ceria nanostructures as a possible novel therapeutic material towards COVID-19 mitigation.

This study reports the synthesis of hybrid nanostructures composed of cerium dioxide and microcrystalline cellulose prepared by the microwave-assisted hydrothermal route under distinct temperature and pH values. Their structural, morphological and spectroscopic behaviors were investigated by X-Rays Diffraction, Field Emission Gun Scanning Electron Microscopy, High-Resolution Transmission Electron Microscopy, and Fourier-Transform Infrared, Ultraviolet-Visible, Raman and Positron Annihilation Lifetime spectroscopies to evaluate the presence of structural defects and their correlation with the underlying mechanism regarding the biocide activity of the studied material. The samples showed mean crystallite sizes around 10 nm, characterizing the formation of quantum dots unevenly distributed along the cellulose surface with a certain agglomeration degree. The samples presented the characteristic Ce-O vibration close to 450 cm-1 and a second-order mode around 1050 cm-1, which is indicative of distribution of localized energetic levels originated from defective species, essential in the scavenging of reactive oxygen species. Positron spectroscopic studies showed first and second lifetime components ranging between 202-223 ps and 360-373 ps, respectively, revealing the presence of two distinct defective oxygen species, in addition to an increment in the concentration of Ce3+-oxygen vacancy associates as a function of temperature. Therefore, we have successfully synthesized hybrid nanoceria structures with potential multifunctional therapeutic properties to be further evaluated against the COVID-19.

Expanding interprofessional teams: Training future health care professionals in screening, brief intervention, and referral to treatment (SBIRT).

INTRODUCTION: Substance misuse persists and is undertreated across the United States (Substance Abuse and Mental Health Services Administration, 2021). Further enhancing the skill sets and capacity of interprofessional members of primary care teams to include proficiency in the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model could help to alleviate the "treatment gap" (those requiring treatment, but not receiving it) by enhancing interprofessional teams at the pregraduate level (e.g., health educators, health coaches) to expand capacity and meet the volume of patients with substance use-related needs. METHOD: In this study, SBIRT knowledge, training satisfaction, and efficacy were evaluated among undergraduate and graduate health and behavioral health students before and after exposure to a series of online training modules. RESULTS: On completion of the training, there were positive percent increases in overall mean knowledge and self-efficacy when compared with pretraining. At posttraining, graduate level students, regardless of discipline, reported greater knowledge than undergraduate students; there were no differences in efficacy or satisfaction among the groups. Additional analysis at the graduate level evaluated differences between behavioral health and medical trainees. No differences were found in knowledge or efficacy between groups at posttest, despite medical trainees reporting significantly lower efficacy at pretest. DISCUSSION: The findings of this study reinforce the need and potential to incorporate SBIRT training into higher education curricula for interprofessional health care professions to begin expanding the integrated care team's knowledge and efficacy in the provision of SBIRT to address the treatment gap. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity.

Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell function during obesity-related inflammatory conditions. The absence of MCT1 impaired CD8+ T cell proliferation with a shift of ATP production to mitochondrial oxidative phosphorylation. In Slc16a1 f/f Tcell cre mice fed a high-fat diet, a reduction in the number of CD8+ T cells, which infiltrated epididymal visceral adipose tissue (epiWAT) or subcutaneous adipose tissue, was observed. Adipose tissue weight and adipocyte area were significantly reduced together with downregulation of adipogenic genes only in the epiWAT. Our findings highlight a distinct effect of MCT1 deficiency in CD8+ T cells in the crosstalk with adipocytes and reinforce the concept that targeting immunometabolic reprogramming in lymphocyte could impact the immune-adipose tissue axis in obesity.

Physical activity and risk of cognitive decline: a meta-analysis of prospective studies.

OBJECTIVE: The relationship between physical activity and cognitive function is intriguing but controversial. We performed a systematic meta-analysis of all the available prospective studies that investigated the association between physical activity and risk of cognitive decline in nondemented subjects. METHODS: We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to January 2010. Studies were included if they analysed prospectively the association between physical activity and cognitive decline in nondemented subjects. RESULTS: After the review process, 15 prospective studies (12 cohorts) were included in the final analysis. These studies included 33,816 nondemented subjects followed for 1-12 years. A total of 3210 patients showed cognitive decline during the follow-up. The cumulative analysis for all the studies under a random-effects model showed that subjects who performed a high level of physical activity were significantly protected (-38%) against cognitive decline during the follow-up (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.54-0.70; P < 0.00001). Furthermore, even analysis of low-to-moderate level exercise also showed a significant protection (-35%) against cognitive impairment (HR 0.65, 95% CI 0.57-0.75; P < 0.00001). CONCLUSION: This is the first meta-analysis to evaluate the role of physical activity on cognitive decline amongst nondemented subjects. The present results suggest a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline.

High sensitivity C-reactive protein predicts the development of new carotid artery plaques in older persons.

BACKGROUND AND AIM: Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated. METHODS AND RESULTS: 486 "InCHIANTI" Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques. Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95%CI 1.5-1.9) and 1.9 (95%CI 1.2-3.1), respectively. Participants with high (>3 µg/mL) and moderate (≥1 and ≤3 µg/mL) CRP levels had a relative risk of 2.2 (95%CI 1.9-2.6) and 1.9 (95%CI 1.6-2.3) respectively, when compared with subjects with low (<1 µg/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significant predictors of the development of new carotid artery plaques. CONCLUSIONS: High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions.