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.

Treating diabetes mellitus in older and oldest old patients.

There is a rapidly growing number of persons reaching extreme age limits. Indeed, the fastest growth is found in those over the age of 80 years or octogenarians. Along with this continuous rise, there is a significant increase in type 2 diabetes in this population. Unfortunately, individuals living past 80 years of age are often accompanied by numerous comorbidities and geriatric conditions, all which render anti-diabetic treatment options challenging. Indeed the principles of managing type 2 diabetes are similar to younger patients. Special considerations in this delicate group are essential due to the increased prevalence of comorbidities and relative inability to tolerate adverse effects of medication and severe hypoglycemia. It is important to recall that octogenarians have shown to have a greater prevalence for cognitive impairment, physical disability, ren al and hepatic dysfunction, and syndromes, such as frailty compared to younger elders. The frailty syndrome is considered one of the most important limitations when treating octogenarians with type 2 diabetes in polypharmacy. Due to the lack of evidence for specific targets of glucose and glycated hemoglobin (A1C) levels in the elderly, available treatment guidelines are based on data extrapolation from younger adults and expert opinion citing reliable evidence. Overall, the most important conclusion emerging from these groups is to accomplish a moderate glycemic control (A1C levels between 7 -8%) in complex elderly patients. However, the risk of hypoglycemia from some treatments may present the greatest significant barrier to optimal glycemic control for the very old. The present review discusses the highlights from the latest guidelines for treating older persons and underlines the need for specific considerations when treating the very old in order to maintain a balance between treating comorbidities and maintaining quality of life.

Diabetes-related quality of life is enhanced by glycaemic improvement in older people.

AIMS: To investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time. METHODS: A total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life. RESULTS: Participants had a mean ± SD age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α = 0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical (r = 0.275; P < 0.001) and mental components (r = 0.291; P < 0.001) of the Short-Form-12 questionnaire. Significant differences were found according to diabetic complications in specific Audit of Diabetes-Dependent Quality of Life items and impact scores. Insulin use had a greater association with a more negative quality of life compared with other antidiabetic agents. A multivariate linear regression model with restricted linear spline application showed that the relationship between HbA1c and impact score was not linear and that the change in the impact score was associated with improved glycaemic control in those with a less negative diabetes-related quality of life at 12 months. CONCLUSIONS: The Audit of Diabetes-Dependent Quality of Life-19 is a valid tool for measuring the impact of diabetes on quality of life in older Italians. Perception of diabetes-related quality of life is associated with glycaemic control over time.

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.

Screening for frailty in elderly emergency department patients by using the Identification of Seniors At Risk (ISAR).

OBJECTIVES: Frail older adults are at an increased risk for adverse outcomes after an Emergency Department (ED) visit. Comprehensive geriatric assessment (CGA) has been proposed to screen for frailty in the ED, but it is difficult to carry out. We tested whether a CGA-based approach using the Identification of Seniors At Risk (ISAR) screening tool was associated with the brief deficit accumulation index (DAI) of frailty. DESIGN: Prospective observational study. SETTING: Two urban EDs in Italy. PARTICIPANTS: A cohort of 200 elderly (≥65 years) ED patients. MEASUREMENTS: Identifiers, triage, clinical and social data along with the administration of ISAR. CGA was performed using: Charlson Index, Short Portable Mental Status Questionnaire and Katz's ADL. Follow-up data at 30 and 180 days included: mortality, ED revisit, hospital admission, and functional decline. Frailty was defined according to a brief DAI. Logistic regression evaluated the consistency of the frailty definition; ROC curves evaluated ISAR ability in identifying frailty. RESULTS: Frailty was present in 117 (58.5%) subjects and predicted ED revisit and frequent ED return, hospitalization and 6-month mortality. ISAR had an AUC of 0.92 (95%CI 0.88-0.96, p<0.0001) in identifying frail elders in the ED and using a cut-off of 2 showed 94% sensitivity and 63% specificity. CONCLUSION: ISAR is a useful screening tool for frailty and identifies elderly patients at risk of adverse outcomes after an ED visit. ISAR can also be used to select high-risk patients more likely to benefit from a geriatric approach or intervention, independently of admission or discharge.

Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction.

The precise cause of sarcopenia, skeletal muscle loss and strength, in older persons is unknown. However, there is a strong evidence for muscle loss due to insulin resistance as well as mitochondrial dysfunction over aging. Considering that epidemiological studies have underlined that insulin resistance may have a specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has also been extensively shown to have a pivotal role on muscle loss in older persons, a combined pathway may not be ruled out. Considering that there is growing evidence for an insulin-related pathway on mitochondrial signaling, we hypothesize that a high degree of insulin resistance will be associated with the development of sarcopenia through specific alterations on mitochondrial functioning. This paper will highlight recent reviews regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance. We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning.

Frailty and muscle metabolism dysregulation in the elderly.

The frailty syndrome is increasingly recognized by geriatricians to identify elders at an extreme risk of adverse health outcomes. The physiological changes that result in frailty are complex and up to now have been extremely difficult to characterize due to the frequent coexistence of acute and chronic illness. Frailty is characterized by an decline in the functional reserve with several alterations in diverse physiological systems, including lower energy metabolism, decreased skeletal muscle mass and quality, altered hormonal and inflammatory functions. This altered network leads to an extreme vulnerability for disease, functional dependency, hospitalization and death. One of the most important core components of the frailty syndrome is a decreased reserve in skeletal muscle functioning which is clinically characterized by a loss in muscle mass and strength (sarcopenia), in walking performance and in endurance associated with a perception of exhaustion and fatigue. There are a number of physiological changes that occur in senescent muscle tissues that have a critical effect on body metabolism. The causes of sarcopenia are multi-factorial and can include disuse, changing hormonal function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. In this review, we will explore the dysregulation of some biological mechanisms that may contribute to the pathophysiology of the frailty syndrome through age-related changes in skeletal muscle mass and function.

PUFA supplements and type 2 diabetes in the elderly.

The prevalence of type 2 diabetes is increasing continuously, especially in older people. Such a rapidly rising risk has been linked to physical inactivity and evolutionary changes in dietary patterns (mainly characterized by a greater intake in dietary fat). Increased physical activity in any age group is associated with a lower risk of developing type 2 diabetes. Epidemiological studies also reported a lower incidence of type 2 diabetes in individuals who consumed n-3 polyunsaturated fatty acids (PUFA), while intake of total, saturated and/or monounsaturated fat was associated with increased risk of type 2 diabetes in glucose-intolerant individuals. Furthermore, the beneficial effects of PUFA consumption on cardiovascular disease were mainly attributed to their effects on reducing triglyceride levels, increasing high density lipoprotein cholesterol, and improving endothelial function through anti-inflammatory mechanisms and reduced platelet aggregation. In addition to common diabetic complications such as dyslipidemia and cardiovascular disease, elderly people with type 2 diabetes are at greater risk of specific geriatric syndromes, such as cognitive decline and physical disability. The threats of physical disability, loss of independence and loss of cognitive performance which diminish quality of life may ultimately be the greatest concern for those with type 2 diabetes. In this review we will address: i) specific dietary fat intake patterns and the development of insulin resistance and type 2 diabetes, ii) the effects of PUFA supplementation on glucose metabolism, diabetic dyslipidemia and cardiovascular disease, iii) the potential advantages of PUFA supplementation on cognitive decline and physical disability in the elderly.

Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.

BACKGROUND: Postprandial plasma glucose (PPG) excursion is a significant determinant of overall metabolic control as well as an increased risk for diabetic complications. Older persons with type 2 diabetes mellitus (DM2) are more likely to have moderate cognitive deficits and neurophysiologic and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for tissue/organ damage in diabetics, the authors hypothesized that PPG excursion is associated with a decline in cognitive functioning and that a tighter control of PPG may prevent cognitive decline. METHODS: Two groups of aged diabetic patients were randomly selected to be treated with repaglinide (n = 77) or glibenclamide (n = 79). RESULTS: Coefficient of variation of PPG (CV-PPG) was associated with Mini-Mental State Examination (MMSE) scores (r = -0.3410; p < 0.001) and a composite score of executive and attention functioning (r = -0.3744; p < 0.001) after adjusting for multiple confounders. Both groups showed a significant decline in hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), but only the repaglinide group demonstrated a significant decline of CV-PPG over time. In models investigating the change in cognitive functioning over time, adjusted for HbA1c and CV-FPG, a decline in cognitive functioning was observed only in the glibenclamide group (p < 0.001). After adjusting for CV-PPG, the authors no longer found a decline in executive and attention functioning composite score (p = 0.085) or the MMSE (p = 0.080) with glibenclamide. CONCLUSIONS: Exaggerated postprandial glucose (PPG) excursions are associated with a derangement of both global, executive, and attention functioning. A tighter control of PPG may prevent cognitive decline in older diabetic individuals.

Plasma glucose excursions in older persons with Type 2 diabetes mellitus.

Type 2 diabetes is a complex and heterogeneous metabolic disorder with a continuously growing prevalence worldwide. Thus, the need to prevent diabetic complications by maintaining better metabolic control has become a common goal for health practitioners. Elevated fasting plasma glucose concentrations, frequently observed in Type 2 diabetic patients, are a marker for disturbances in glucose control which can lead to subsequent complications. However, such levels may be considered an incomplete index of glucose control in light of the fact that mealtime glucose excursions are also responsible for overall glucose control. Recently, studies have underlined the fact that plasma glucose fluctuations, such as those occurring in an absorptive state, may not only be an important determinant of overall glucose control and risk of diabetic complications, but they may also exert an independent negative effect on the long-term outcome of diabetes. Many mechanisms have been described by which mealtime glucose excursion could pose a potential risk factor for cardiovascular disease in diabetic patients. Acute elevations of plasma glucose concentrations trigger an array of tissue response that may contribute to the development of vascular complications. Therefore, we will discuss how post-prandial glucose excursions are a fundamental risk factor for the development of cardiovascular disease, especially in older persons with Type 2 diabetes.

Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver.

AIM: To define the characteristics of the Italian patient presenting non-alcoholic fatty liver disease. PATIENTS AND METHODS: A total of 305 patients with abnormally high plasma aminotransferase and/or gamma-glutamyl-transpeptidase levels for at least 12 months, with no known cause of chronic liver damage, were consecutively enrolled in the study. Clinical, routine biochemical and liver histology investigations were carried out in all patients. Also evaluated were: (a) oral glucose load; (b) insulinaemia and insulin-resistance using the HOMA test model; and (c) plasma endotoxaemia, total antioxidant plasma capability, tumour necrosis factor-alpha, plasma interleukin-6 and -10 levels. Malondialdehyde and 4-hydroxynonenal content were determined on liver samples from 120 patients. RESULTS: The majority of patients were young overweight or obese males, with dyslipidaemia (20-60%), diabetes (10.5%), hyperinsulinaemia (40%), hyperferritinaemia (35%). Endotoxaemia was negative in all patients and cytokines were only sporadically altered. Total antioxidant plasma capability was decreased in 38.4% of the patients. Eighty percent of the cases had histological steatosis with a mild degree of inflammation and fibrosis. Seven patients had cirrhosis. Lipid peroxidation markers were increased in 90% of the cases, inversely correlated with fibrosis. Even if at univariate analysis, age, ferritin and tissue 4-hydroxynonenal were independent factors of steatosis (P < 0.01), and insulin, HOMA and ferritin of inflammation and fibrosis (P < 0.01), at multivariate analysis no single factor was found to be an independent predictor of hepatic lesions. CONCLUSIONS: The typical Italian patient with non-alcoholic fatty liver disease is a young male, obese, not diabetic, with a variable incidence of dyslipidaemia and hyperinsulinaemia. Only liver biopsy may define the type of liver damage.