Multidimensional Prognostic Index (MPI) in elderly patients with acute myocardial infarction.

BACKGROUND: Management of elderly patients with acute myocardial infarction (AMI) is challenging due to lack of knowledge about the link between fragility, outcomes and interventional procedures. AIMS: The aim of this study was to establish the prognostic role of the Multidimensional Prognostic Index (MPI) in elderly with AMI. METHODS: A total of 241 patients ≥ 65 years old with AMI were continuously enrolled in this prospective study and divided into three groups according to the MPI score. The primary endpoint was 30-day mortality. Secondary endpoints were 6-month mortality and rate of adverse events. RESULTS: In-hospital overall mortality rate was higher in MPI-3 (p = 0.009). Patients of MPI-3 had a significantly higher mortality rate regarding the primary endpoint with 30-day survival of 78.9%, compared to 97.4% and 97.2%, in MPI-1, MPI-2 (p < 0.001), respectively. The survival rate progressively decreased in the three MPI classes of risk with a 6-month survival of 96.5%, 96.3%, 73.7% in groups MPI-1, MPI-2, and MPI-3 (p < 0.001). Longer length of in-hospital stay was observed in MPI-3 group. In-hospital complications were more frequent in higher MPI score. DISCUSSION: Our findings are in agreement with the results of other studies that evaluated the risk of in-hospital complications and mortality in older patients. In our "real-world" population of elderly hospitalized for AMI we observed poorer outcomes in patients belonged to higher MPI groups. CONCLUSIONS: In the setting of AMI, MPI may be very useful in the daily clinical practice to manage older patients and predict the risk of in-hospital and follow-up complications.

Validation of a Brief Form of the Self-Administered Multidimensional Prognostic Index: The SELFY-BRIEF-MPI Project.

In clinical practice, self-administered and brief tools to promptly identify older people at risk of frailty are required. The Multidimensional Prognostic Index (MPI), derived from the Comprehensive Geriatric Assessment (CGA) seems reliable enough to serve this purpose, but despite the several versions developed over the past 15 years, it lacks a self-administered and brief version. In this study, we aimed to evaluate the agreement between an abbreviated form of the SELFY-MPI (i.e., SELFY-BRIEF-MPI) and the standard version of the MPI. Four Italian hospitals consecutively enrolled outpatients and inpatients >65 years. The sample included 105 participants (mean age = 78.8 years, 53.3% females). Overall, the two versions showed non-statistically significant differences (Standard-MPI 0.42 ± 0.19 vs.. SELFY-BRIEF-MPI 0.41 ± 0.18; p = 0.104) and a very strong correlation (R = 0.86, p < 0.001). The Bland-Altman Plot revealed that only 5/105 measurements (4.76%) were outside the limits of agreement. The accuracy of the SELFY-BRIEF-MPI in identifying frail people (defined as a Standard-MPI > 0.66) was optimal (area under the curve, AUC = 0.90, p < 0.001). To predict multidimensional frailty, a SELFY-BRIEF-MPI score of 0.60 exhibited the greatest sensitivity/specificity ratio. In conclusion, the SELFY-BRIEF-MPI reported a good agreement with the standard version of the MPI, indicating its application in the screening of multidimensional frailty among older people.

Validation of Abbreviated Form of the Multidimensional Prognostic Index (MPI): The BRIEF-MPI Project.

Purpose: To screen multidimensional frailty in older people, using a comprehensive geriatric assessment (CGA) tool such as the multidimensional prognostic index (MPI), is a public health priority. Unfortunately, the screening tools available are not able to capture multidimensional frailty. In this work, we aimed to evaluate in a population of hospitalized and ambulatory older patients, the agreement between an abbreviated form of the MPI (ie, BRIEF-MPI) and the standard/full version. Participants and Methods: All participants included in the study completed both versions of the MPI, brief and full, which share the following domains: 1) basic and 2) instrumental activities of daily living, 3) mobility/risk of pressure sores, 4) cognition, 5) nutrition, 6) comorbidity, 7) social and 8) number of medications. The agreement between the two instruments was reported using either the mean comparisons with a t-test matched sample, a simple correlation analysis and the Bland-Altman methodology. Results: The study sample included 110 participants (mean age=83.2 years, 51.8% women). The mean difference was statistically and clinically irrelevant (mean difference=0.01±0.10; p=0.27). The correlation between brief and full MPI versions was optimal (R=0.82, p<0.0001). Using the Bland-Altman methodology, we observed that only three participants over 110 (=2.73%) were outside the limits of agreement. The accuracy of BRIEF-MPI in predicting multidimensional frailty, as full MPI>0.66, was optimal (area under the curve=0.92, p<0.0001). A BRIEF-MPI value of 0.59 yielded the highest sensitivity and specificity in predicting multidimensional frailty. Conclusion: BRIEF-MPI had a good agreement with the full/standard version of the MPI, making this tool as ideal for the screening of multidimensional frailty in older people.

Multidimensional frailty increases cardiovascular risk in older people: An 8-year longitudinal cohort study in the Osteoarthritis Initiative.

BACKGROUND: Cardiovascular diseases (CVDs) are the most important cause of mortality and an important cause of disability. Frailty seems to be associated with higher cardiovascular risk, but limited research has been done using a multidimensional approach to frailty. Thus, the present study aimed to investigate whether the multidimensional prognostic index (MPI), based on comprehensive geriatric assessment (CGA), is associated with CVD risk in the Osteoarthritis Initiative (OAI) study. METHODS: Community-dwellers affected by knee OA or at high risk for this condition were followed for 8 years. A standardized CGA including information on functional, nutritional, mood, comorbidities, medications, quality of life and co-habitation status was used to calculate a modified version of the MPI (range 0-1), with higher scores representing greater risk of mortality. CVDs were recorded using self-reported information. Logistic regression analyses, adjusting for potential confounders, were conducted. RESULTS: The final sample consisted of 4211 individuals (mean age 60.8 years, females = 58.6%). People with incident CVD had a significant higher baseline MPI value than those without CVD (0.44 ± 0.17 vs. 0.39 ± 0.17). People with an MPI between 0.34 and 0.66 (OR = 1.31; 95%CI: 1.03-1.67) and over 0.66 (OR = 1.91; 95%CI: 1.26-2.89) experienced a higher risk of CVD (vs. MPI score < 0.34). A 0.10 points increase in the MPI score at baseline was associated with a 1.16 (95%CI: 1.09-1.24) times higher odds for incident CVD. CONCLUSIONS AND IMPLICATIONS: Higher MPI values at baseline were associated with an increased risk of CVD, reinforcing the importance of CGA in predicting CVD risk in older people.

Multidimensional prognostic index (MPI) predicts non-invasive ventilation failure in older adults with acute respiratory failure.

BACKGROUND: Acute respiratory failure (ARF) is a very common complication among hospitalized older adults. Non-invasive ventilation (NIV) may avoid admission to intensive care units, intubation and their related complication, but still lacks specific indications in older adults. Multidimensional Prognostic Index (MPI) based on comprehensive geriatric assessment (CGA) could have a role in defining the short-term prognosis and the best candidates for NIV among older adults with ARF. METHODS: This is a retrospective observational study which enrolled patients older than 70 years, consecutively admitted to an acute geriatric unit with ARF. A standardized CGA was used to calculate the MPI at admission. Multivariate Cox regression models were used to test if MPI score could predict in-hospital mortality and NIV failure. Receiver operator curve (ROC) analysis was used to identify the discriminatory power of MPI for NIV failure. RESULTS: We enrolled 231 patients (88.2 ± 5.9 years, 47% females). Mean MPI at admission was 0.76±0.16. In-hospital mortality rate was 33.8%, with similar incidence in patients treated with and without NIV. Among NIV users (26.4%), NIV failure occurred in 39.3%. Higher MPI scores at admission significantly predicted in-hospital mortality (ß=4.46, p<0.0001) among patients with ARF and NIV failure (ß=7.82, p = 0.001) among NIV users. MPI showed good discriminatory power for NIV failure (area under the curve: 0.72, 95% CI: 0.58-0.85, p<0.001) with optimal cut-off at MPI value of 0.84. CONCLUSIONS: MPI at admission might be a useful tool to early detect patients more at risk of in-hospital death and NIV failure among older adults with ARF.

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Fatigue is one of the conditions most frequently complained by the elderly. There are few effective treatment options for patients with chronic fatigue syndrome. To determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl L-carnitine (ALC), 96 aged subjects (>70 years, range 71-88) were investigated (50 females and 46 males; mean age 76.2+/-7.6 and 78.4+/-6.4 years, respectively). They met four or more of the Holmes major criteria or at least six of Fukuda minor criteria. Fatigue was measured with the Wessely and Powell [Wessely, S., Powell, R., 1989. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J. Neurol. Neurosurg. Psychiatry 52, 940-948] scores, with the fatigue severity scale. At the end of the treatment, we observed a decrease of physical fatigue: 6.2 (p<0.001), of mental fatigue: 2.8 (p<0.001), of severity fatigue: 21.0 (p<0.001) and improvements in functional status: 16.1 (p<0.001) and cognitive functions: 2.7 (p<0.001). By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain -27% versus -3% (p<0.05); prolonged fatigue after exercise: 51% versus -4% (p<0.0001); sleep disorders: 28% versus 4% (p<0.05); physical fatigue: 7 versus -0.5 (p<0.0001); mental fatigue: -3.3 versus 0.6 (p<0.0001); fatigue severity scale: -22.5 versus 1.2 (p<0.0001); functional status 17.1 versus 0.6 (p<0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5 (p<0.0001). Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions.

Frailty and the gut.

Frailty, which is a syndrome that encompasses losses in physical, psychological and social domains, is responsible for enhanced vulnerability to endogenous and/or exogenous stressors. Frailty is a public health problem for an ageing society; however, it is poorly understood and often under-recognised in clinical settings. In particular, the impact of frailty on either intestinal functions, i.e. immune response, permeability, and absorption, or gut microbiota composition is as yet mostly unexplored. A better comprehension of the intestinal dysfunction occurring in the elderly would help in clarifying the mechanisms predisposing frail patients to a higher risk of infectious or inflammatory events. Moreover, recent evidence suggests that senescence-induced perturbations of the gut-brain axis are involved in the neuroinflammation process, thus raising the hypothesis that preserving gut permeability and preventing frailty-related changes in the microbiota composition might reduce the susceptibility to develop neurodegenerative disorders. In this review, we highlight the current insights concerning the relationship between frailty, intestinal functions, microbiota, and gut-brain axis.

L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial.

BACKGROUND: Centenarians are characterized by weakness, decreasing mental health, impaired mobility, and poor endurance. L-Carnitine is an important contributor to cellular energy metabolism. OBJECTIVE: This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians. DESIGN: This was a placebo-controlled, randomized, double-blind, 2-phase study. Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study. The 2 groups received either 2 g levocarnitine once daily (n = 32) or placebo (n = 34). Efficacy measures included changes in total fat mass, total muscle mass, serum triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, Mini-Mental State Examination (MMSE), Activities of Daily Living, and a 6-min walking corridor test. RESULTS: At the end of the study period, the levocarnitine-treated centenarians, compared with the placebo group, showed significant improvements in the following markers: total fat mass (-1.80 compared with 0.6 kg; P < 0.01), total muscle mass (3.80 compared with 0.8 kg; P < 0.01), plasma concentrations of total carnitine (12.60 compared with -1.70 mumol; P < 0.05), plasma long-chain acylcarnitine (1.50 compared with -0.1 micromol; P < 0.001), and plasma short-chain acylcarnitine (6.0 compared with -1.50 micromol; P < 0.001). Significant differences were also found in physical fatigue (-4.10 compared with -1.10; P < 0.01), mental fatigue (-2.70 compared with 0.30; P < 0.001), fatigue severity (-23.60 compared with 1.90; P < 0.001), and MMSE (4.1 compared with 0.6; P < 0.001). CONCLUSIONS: Our study indicates that oral administration of levocarnitine produces a reduction of total fat mass, increases total muscular mass, and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions.

Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout.

Hyperuricemia is a feature of several pathologies and requires an appropriate and often early treatment, owing to the severe consequences that it may cause. A rapid and massive raise of uric acid, during tumor lysis syndrome (TLS), and also a lower and chronic hyperuricemia, as in gout, mainly damage the kidney. To prevent or treat these consequences, a new therapeutic option is represented by rasburicase, a recombinant form of an enzyme, urate oxidase. This enzyme converts hypoxanthine and xanthine into allantoin, a more soluble molecule, easily cleared by kidney. The several types of urate oxidase have followed each other, with progressive reduction of adverse reactions. The most important among them are allergenicity and the development of antibodies which compromise their effectiveness. Nevertheless, a limit of rasburicase's use remains its cost, which obliges to a judicious choice to prevent TLS in high risk patients with cancer and in case of allergy or impossibility to take allopurinol orally both in TLS and in gout. A large body of evidence confirms the efficacy and safety of rasburicase, even in comparison to the standard drugs used in the aforementioned pathologies.

Losartan vs. amlodipine treatment in elderly oncologic hypertensive patients: a randomized clinical trial.

Elderly neoplastic patients frequently may show hypertension and hyperuricemia, before and after chemotherapeutic treatments. The purpose of this study was to evaluate the efficacy of losartan which is an antihypertensive drug with uricosuric properties vs. amlodipine in hypertensive neoplastic elderly patients. This was an open-labeled, randomized, comparative trial. The study was performed as a 30-day study. Seventy patients with cancer were randomly assigned to receive losartan or amlodipine. Blood pressure (BP), blood urea nitrogen (BUN) levels, creatinine, serum and urinary uric acid, creatinine and uric acid clearance were determined before and after chemotherapy. One day after chemotherapy in losartan group vs. amlodipine group we observed a significant difference in urinary uric acid (p<0.001) of 18 mg/24 h vs. 40 mg/24 h. Thirty days after chemotherapy we observed a significant difference in azotemia of 0.0 mg/dl vs. 3.8 mg/dl (p<0.001), serum uric acid of 0.05 mg/dl vs. 0.49 mg/dl (p<0.001), urinary uric acid (p<0.001) of 23 mg/24 h vs. 0.0 mg/24 h, GFR of 2 ml/min/1.73 m(2) vs. -8 ml/min/1.73 m(2) (p<0.05) and systolic BP (SBP) of 3.6 mmHg vs. 0.8 mmHg (p<0.05). The findings of the present study support the effective role of losartan compared to amlodipine in treating hypertension and hyperuricemia in elderly patients under chemotherapeutic treatment.

L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes.

BACKGROUND: Patients with type 2 diabetes are under high oxidative stress, and levels of hyperglycemia correlate strongly with levels of LDL oxidation. Carnitine favorably modulates oxidative stress. OBJECTIVE: This objective of this study was to evaluate the efficacy of L-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes. DESIGN: Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g L-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B-100, oxidized LDL cholesterol, thiobarbituric acid-reactive substances, and conjugated dienes. RESULTS: At the end of the study period, the L-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers: oxidized LDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001); LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001); apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05); apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid-reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001). CONCLUSION: Our study indicates that oral administration of L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.

Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study.

OBJECTIVE: Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. METHODS: Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. RESULTS: After 60 min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40 mumol P<0.05. After 1 day of the study period, the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgow's score: 3.60 versus 1.50 score P<0.05; a significant decrease of ammonia serum levels: 63.30 versus 27.00 mumol P<0.01; a significant improvement of EEG cps/s: 2.70 versus 0.6 P<0.001. No side-effects were observed in our study series. CONCLUSION: Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

Elevated chromogranin A (CgA) serum levels in the patients with advanced pancreatic cancer.

The neuroendocrine differentiation in PC could potentially represent a new finding with diagnostic, prognostic and therapeutic implications. This study aimed at evaluating the clinical usefulness of CgA as a neuroendocrine (NE) serum-marker. We investigated the role of the serum concentration of CgA in a study group of patients with PC. CgA was significantly higher in the patients affected by PC as compared with the group of healthy subjects (HS) and those with chronic pancreatitis (CHP) (p<0.001). Also the HS group differed significantly from the CHP control group in the serum CgA levels (p<0.001). The serum carbohydrate antigen (CA19-9) level displayed a significant difference (p<0.001) between the PC and the HS group. The PC and CHP groups, as well as the HS and CHP groups showed also significant differences in the CA19-9 levels (p<0.001). One can conclude that the patients with higher CgA levels had poorer prognosis and survival, as compared to those with lower CgA levels. These results support the notion that the determination of serum CgA level before treatment may be a potential prognostic factor for PC.

Acetyl-L-carnitine treatment in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) is characterized by disturbance of mental state and neuromuscular function. To assess the clinical efficacy of acetyl-L: -carnitine (ALC) in the treatment of MHE, we performed a randomized, double-blind, placebo-controlled study administering ALC in cirrhotic patients with this disease and evaluating their cognitive functions. One hundred and twenty-five cirrhotic patients, of whom 21 were infected by hepatitis B virus, 75 by hepatitis C virus and 29 with cryptogenic cirrhosis, were enrolled in our study. Patients were randomly divided into two groups, and using double-blind administration, group A was treated with ALC and group B with placebo for 90 days. The two groups were similar in demographic characteristics, aetiology of cirrhosis, duration and Child-Pugh grade. Minimal hepatic encephalopathy was diagnosed with the Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT) and Auditory Verbal Learning Test (AVL) and cognitive function with the Mini Mental State Examination (MMSE). After 90 days in group A treated with ALC, we observed a significant decrease in prothrombin time (P < 0.001), bilirubin serum levels (P < 0.01), AST (P < 0.001), fasting NH(4) serum levels (P < 0.001), Trail Making Test-A (P < 0.001) and Trail Making Test-B (P < 0.001), and a significant increase in albumin serum levels (P < 0.005), MMSE test (P < 0.001), Symbol Digit Modalities Test (P < 0.001), BDT (P < 0.001), AVL long-term test (P < 0.001) and AVL total test (P < 0.001). No significant differences were observed in EEG in either group of patients treated with ALC or placebo. The benefits of ALC in comparison with placebo are demonstrated in greater reductions in serum ammonia levels, as well as in improvements of neuropsychological functioning.

L-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha-interferon and ribavirin.

BACKGROUND: Hepatic steatosis is a common presentation in patients with chronic hepatitis C. Interferon alpha exerts both antiviral and immunomodulating actions, and influences on lipid metabolism. The aim of our study was to test whether L-carnitine reduces steatosis in patients treated with interferon and ribavirin. PATIENTS AND METHODS: A total of 70 patients were randomly assigned to receive either leucocyte IFN alpha at a dose of 3 MIU thrice a week plus 1,000 mg ribavirin per day for 12 months (group A) or IFN alpha and ribavirin at the same dose plus 2 g carnitine per day (group B). RESULTS: Comparison of the two treatments showed significant differences between the mean values of the following parameters at the end of the treatment: ALT -68 vs -95 IU/ml (P < 0.05), total cholesterol 0.08 vs -0.91 mmol/l (P < 0.05) and triglycerides +0.25 vs -20 mmol/l (P < 0.05); and at the follow-up: AST -35 vs -65 IU/ml (P < 0.05) and ALT -55 vs -84 IU/ml (P < 0.05). All values were lower in group B (IFN + Ribavirin + Carnitine) than in group A (IFN plus Ribavirin). When comparing those patients treated with IFN + ribavirin with those treated with IFN plus ribavirin plus carnitine, the response at the end of the treatment was 48% vs 56%, and the sustained response 39% vs 46%, respectively. CONCLUSIONS: Combined treatment with L: -carnitine, ribavirin and IFN alpha resulted in greater antihyperlipidaemic effects and than with ribavirin and IFN alpha alone. The results of this study suggest that L: -carnitine may have a role among the reduction of steatosis strategies in patients with hepatitis C treated with IFN alpha and ribavirin.

Sexual dysfunction in chronic hepatitis C virus patients treated with interferon alpha and ribavirin.

The effects on sexual behavior in patients with chronic hepatitis C treated with IFN alpha plus ribavirin is an understudied field. The aim of our study was to evaluate this treatment on sexual behavior. We enrolled 170 male patients affected by chronic hepatitis C that received three MIU intramuscular leukocyte Interferon alpha plus Ribavirin thrice a week for 12 months. We assessed IFN influence by using the responses to International Index of Erectile Function (IIEF). The baseline values of each IIEF score were compared to those obtained at the end of months 1, 3, 6, and 12 as well as at the end of the follow-up period. At the end of month 1, we detected a significant reduction of IIEF scores with respect to basal values, for all administered items. These values were similar to those found at the end of month 3 for almost all parameters, being increased in only the scores of erectile function. At the end of treatment, all scores appeared reincreased, but only mean score of erectile function appeared similar to pretreatment value. The organism adapts itself in someway to the action of cytokine. Psychological influence of IFN on the patients could justify the partial impairment of sensation linked to sexual behavior. Our study provided some more information in quantification and qualification of sexual disturbances related to IFN plus Ribavirin administration in the treatment of chronic hepatitis C.