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ObjectivesThere has been growing research interest in loneliness and wisdom in recent decades, but no cross-cultural comparisons of these constructs using standardized rating measures in older adults, especially the oldest-old. This was a cross-sectional study of loneliness and wisdom comparing middle-aged and oldest-old adults in Cilento, Italy and San Diego, United States.MethodWe examined loneliness and wisdom, using the UCLA Loneliness Scale Version 3 (UCLA-3) and San Diego Wisdom Scale (SD-WISE), respectively, in four subject groups: adults aged 50-65 and those ≥90 years from Cilento, Italy (N = 212 and 47, respectively) and San Diego, California, USA (N = 138 and 85, respectively).ResultsAfter controlling for education, there were no significant group differences in levels of loneliness, while on SD-WISE the Cilento ≥90 group had lower scores compared to the other three groups. There was a strong inverse correlation between loneliness and wisdom in each of the four subject groups. Loneliness was negatively associated while wisdom was positively associated with general health, sleep quality, and happiness in most groups, with varying levels of significance.ConclusionThese results largely support cross-cultural validity of the constructs of loneliness and wisdom, and extend previous findings of strong inverse correlations between these two entities. Loneliness has become a growing public health problem, and the results of our study suggest that wisdom could be a protective factor against loneliness, although alternative explanations are also possible. Research on interventions to reduce loneliness by enhancing wisdom in older adults is needed.

Background: Nonagenarians and centenarians (NCs) are an extremely fragile population, particularly in regard to their physical and cognitive function. The aim of this study was to define the neurocognitive profiles among 29 NCs and their 49 younger cohabitants aged 50-75 years from The Cilento Initiative on Aging Outcomes (CIAO) Pilot study in the South of Italy that had provided initial hypotheses regarding positive psychological traits related to exceptional longevity. Methods: During the home visits, lifestyle information with specific questionnaires, functional autonomy and the neuropsychological Mini Mental Scale Examination (MMSE), and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scale were obtained by qualified study personnel. The total blood oxidative capacity was also determined by testing the reactive derivative of oxygen metabolites (d-ROM) and by the Biological Antioxidant Potential (BAP). In all individuals, the APOE genotype determination was also performed. Results: All the subjects in both groups showed high adherence to the Mediterranean Diet. None of the NCs had severe cognitive impairment, and a very low incidence of dementia was found. The data obtained on the Activities ed Instrumental Activities of Daily Living (ADL-IADL) scale showed that the majority of NCs (16/29) were autonomous in daily life activities. The comparative assessment of NCs and cohabitants showed no significant differences in the laboratory assessment of oxidative stress and APOE genotype. Conclusion: In the Cilento Region of Southern Italy, NCs seemed to have good cognitive status when compared to younger cohabitants aging 50-65 years without significant differences in oxidative stress markers or APOE genotype. These results might be related to optimal adherence to the Mediterranean diet, although other lifestyle factors and positive personality traits may also contribute to their healthy aging. Further studies on a larger population should be performed to confirm the results of this pilot study.

OBJECTIVE:This was a study of positive psychological traits in a group of rural Italians aged 90 to 101 years, and their children or other family members. DESIGN:Mixed-methods quantitative (standardized rating scales) and qualitative (semi-structured interviews) study. SETTING:Study participants' homes in nine villages in the Cilento region of southern Italy. PARTICIPANTS:Twenty-nine nonagenarians and centenarians and 51 family members aged 51-75 years, selected by their general practitioners as a part of a larger study called CIAO (Cilento Initiative on Aging Outcomes). METHODS:We used published rating scales of mental and physical well-being, resilience, optimism, anxiety, depression, and perceived stress. Qualitative interviews gathered personal narratives of the oldest-old individuals, including migrations, traumatic events, and beliefs. Family members described their impressions about the personality traits of their older relative. RESULTS:Participants age ≥90 years had worse physical health but better mental well-being than their younger family members. Mental well-being correlated negatively with levels of depression and anxiety in both the groups. The main themes that emerged from qualitative interviews included positivity (resilience and optimism), working hard, and bond with family and religion, as described in previously published studies of the oldest old, but also a need for control and love of the land, which appeared to be unique features of this rural population. CONCLUSIONS:Exceptional longevity was characterized by a balance between acceptance of and grit to overcome adversities along with a positive attitude and close ties to family, religion, and land, providing purpose in life.

Objective: Obesity is a key risk factor for type 2 diabetes; however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI and subsequently to test whether lean individuals who carry an obese metabolome are at hidden high risk of obesity-related diseases, such as type 2 diabetes.Research Design and Methods: Levels of 108 metabolites were measured in plasma samples of 7,663 individuals from two Swedish and one Italian population-based cohort. Ridge regression was used to predict BMI using the metabolites. Individuals with a predicted BMI either >5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further investigated for obesity-related risk factors and future risk of type 2 diabetes and mortality.Results: The metabolome could predict BMI in all cohorts (r2 = 0.48, 0.26, and 0.19). The overestimated group had a BMI similar to individuals correctly predicted as normal weight, had a similar waist circumference, were not more likely to change weight over time, but had a two times higher risk of future type 2 diabetes and an 80% increased risk of all-cause mortality. These associations remained after adjustments for obesity-related risk factors and lifestyle parameters.Conclusions: We found that lean individuals with an obesity-related metabolome have an increased risk for type 2 diabetes and all-cause mortality compared with lean individuals with a healthy metabolome. Metabolomics may be used to identify hidden high-risk individuals to initiate lifestyle and pharmacological interventions. [ABSTRACT FROM AUTHOR]

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods: This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results: Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)²/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P<0.05). The T0 NephroCheck value predicted 30-day mortality (AUC, 0.68; P<0.001). Conclusions: NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or rulingout of AKI in the ED. [ABSTRACT FROM AUTHOR]

BACKGROUND: The value proposition for biosimilars can be characterized as a concept that moves beyond the argument of cost reduction relative to the innovator biologic drug and into a framework that incorporates the diverse needs of key healthcare stakeholders during the transition from clinical development to commercialization in the marketplace. OBJECTIVES: To identify factors that facilitate and inhibit the development, commercialization, and adoption of biosimilars, and to recommend modifications in program design that are likely to support the demonstration of the value of biosimilars for payers, providers, and patients. METHODS: The primary data sources for this article include surveys conducted by Boston Healthcare Associates with payers and clinicians in the United States and the European Union 5 markets and blinded international protocol feasibility assessments completed by Worldwide Clinical Trials. Survey methodology used either convenience or purposeful sampling as appropriate, with participants extracted from diverse audiences, representative of those who generate or evaluate clinical data shaping the economic exchange and preferential status influencing physician adoption and patient access to biosimilars. Patient characteristics and psychosocial issues influencing patients' perception of small-molecule generics were extracted from the available literature to inform exploratory hypotheses, given the relative absence of such information for biosimilars. DISCUSSION: This article reviews the current evidence and summarizes results of surveys conducted with payers, providers, and drug investigation sites in the United States. Based on a review of published literature, as well as these survey results, conflicting and convergent demands exist for gathering data related to biosimilars. The motivations and data needs for these new agents are diverse, requiring adjudication of regulatory, economic, and clinical incentives beginning at program inception and extending through commercialization of the final biosimilar agent. CONCLUSIONS: The development and commercialization of biosimilars represent an international activity that can encounter unanticipated challenges, as well as opportunities to achieve clinical and commercial success. Evolving regulatory guidance mapped in relation to payer, physician, and patient sentiments may inform the biosimilar development program designs, implementation, and positioning of the new drug. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome is a leading cause of morbidity and mortality in patients with schizophrenia, with a prevalence rate double that of nonpsychiatric populations. Given the amount of evidence suggesting a link between atypical antipsychotic medications and metabolic syndrome, several agencies have recommended regular clinical monitoring of weight, symptoms of hyperglycemia, and glucose in chronically medicated patients with schizophrenia. Objectives: To summarize the current literature on atypical antipsychotic-induced metabolic syndrome in patients with schizophrenia, outline some of the molecular mechanisms behind this syndrome, identify demographic and disease-related risk factors, and describe cost-effective methods for surveillance. Discussion: The differential prevalence of metabolic syndrome associated with various atypical antipsychotic medications has been evidenced across numerous studies, with higher effects seen for certain antipsychotic medications on weight gain, waist circumference, fasting triglyceride level, and glucose levels. Given the association of these symptoms, all atypical antipsychotic medications currently include a warning about the risk of hyperglycemia and diabetes, as well as suggestions for regular monitoring. Despite this, very little data are available to support adherence to these monitoring recommendations. Lack of awareness and resources, diffusion of responsibility, policy implementation, and organizational structure have all been implicated. Conclusion: The treatment of schizophrenia involves a balance in terms of risks and benefits. Failing to treat because of risk for complications from metabolic syndrome may place the patient at a higher risk for more serious health outcomes. Supporting programs aimed at increasing monitoring of simple laboratory and clinical measures associated with metabolic syndrome may decrease important risk factors, improve patients' quality of life, and reduce healthcare costs. [ABSTRACT FROM AUTHOR]

Background: Research and development activities in an era of globalization encounter a mosaic of providers, products, services, and intermediaries; regulatory and other government institutions; and consumers. The introduction of novel therapeutics into this environment mandates research programs that are relevant to the registration process, payers and purchasers, transparent pricing, and rule-driven business practices, while providing data relevant to marketing initiatives internationally. Objective: To outline an example for clinical development programs that incorporate the perspective of multiple stakeholders into a portfolio of study designs to provide optimal data platforms that can resonate with diverse recipients. Discussion: A contract research organization directly involved in the design, execution, and analysis of clinical trials for new drugs and devices across pharmaceutical and biotechnology companies provides a unique perspective regarding opportunities and challenges within the international clinical research environment. Drs Murphy, Antonini, and Lai, representing Worldwide Clinical Trials, utilize chronic obstructive pulmonary disease as a demonstration project exploiting its prevalence, direct and indirect costs, and the rapid infusion/diffusion of innovative therapy into practice as a rationale for focus, and illustrate methods of informing registration and technology assessments during a prototypical development process. Conclusion: By virtue of its chronicity, prevalence, and pattern of healthcare utilization, chronic obstructive pulmonary disease provides an ideal case for illustrating the application of clinical trial methodology that can facilitate data evaluation through the prism of multiple stakeholders. Adding an international dimension exacerbates system complexity and serves to illustrate the breadth of issues that can be addressed within this therapeutic area. [ABSTRACT FROM AUTHOR]

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED., Methods: This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses., Results: Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m) 2 /1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P =0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development ( P <0.05). The T0 NephroCheck value predicted 30-day mortality (AUC, 0.68; P <0.001)., Conclusions: NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.