A systematic review and meta-analysis assessing adverse event profile and tolerability of nicergoline.

OBJECTIVE: To evaluate the safety profile of nicergoline compared with placebo and other active agents from published randomised controlled trials. DESIGN: Systematic review and meta-analysis of nicergoline compared with placebo and other active agents across various indications. DATA SOURCES: MEDLINE, Medline-in-process, Cochrane, EMBASE, EMBASE alerts, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR) and Cochrane Methodology Register (CMR) for all the randomised controlled trials, open-label or blinded, in adults treated with nicergoline. Studies published until August 2013 were included. REVIEW METHOD: 29 studies were included for data extraction. The studies included in this review were majorly from European countries and mostly in cerebrovascular disease (n=15) and dementia (n=8). RESULTS: The treatment withdrawals were comparatively lower in the nicergoline group as compared with the placebo group (RR=0.92; 95% CI 0.7 to 1.21) and other active comparators (RR=0.45; 95% CI 0.10 to 1.95), but the difference was non-significant. Incidence of any adverse events (AEs) was slightly higher (RR=1.05; 95% CI 0.93 to 1.2) while incidence of serious AEs was lower (RR=0.85; 95% CI 0.50 to 1.45) in the nicergoline compared with placebo group. Frequency of anxiety was significantly lower in nicergoline as compared with placebo (p=0.01). Other AEs including diarrhoea, gastric upset, dizziness and drowsiness were less frequent in the nicergoline group when compared with placebo/active drugs, but the difference was non-significant. Frequency of hypotension and hot flushes was slightly higher in the nicergoline group but the difference was non-significant. None of the studies reported any incidence of fibrosis or ergotism with nicergoline treatment. CONCLUSIONS: Nicergoline is an ergot derivative, but its safety profile is better than other ergot derivatives like ergotamine and ergotoxine. This systematic review and meta-analysis suggests that nicergoline has a good safety profile. None of the studies included in this systematic review reported any incidence of fibrosis or ergotism with nicergoline.

Is urinary 1-hydroxypyrene a valid biomarker for exposure to air pollution in outdoor workers? A meta-analysis.

The aim of this study was to evaluate the usefulness and specificity of urinary 1-hydroxypyrene (1-OHPu) as a biomarker of the exposure from urban pollution to polycyclic aromatic hydrocarbons (PAHs) among outdoor workers in a meta-analysis. Our meta-analysis was performed according to standard methods, and the results show that the concentrations of 1-OHPu tend to be higher in exposed workers than in unexposed workers (if we exclude two highly heterogeneous articles), in exposed non-smokers than in unexposed non-smokers and in exposed than in unexposed workers who were carriers of the CYP1A1 genotype and in those with the glutathione-S-transferase M1 (-)genotype. These genotypes enhance the effect of exposure, particularly in non-smokers. Smoking reduces the differences between exposed and unexposed subjects. In conclusion, our results suggest that the use of the 1-OHPu biomarker appears to be reliable for studying occupational exposure to PAHs from urban pollution, as long as environmental and behavioural factors are considered.

Cadmium and hypertension in exposed workers: A meta-analysis.

OBJECTIVES: In the general population, cadmium seems to be responsible for hypertension, atherosclerosis and an increase in acute coronary events. Therefore, the purpose of this meta-analysis was to analyze controlled studies conducted on cadmium and arterial pressure in occupationally-exposed workers. MATERIALS AND METHODS: After analyzing all the relevant articles found in the literature, 6 publications were selected. RESULTS: A higher prevalence of hypertension and higher values of systolic and diastolic blood pressure were recorded in the exposed subjects. CONCLUSIONS: Cadmium in occupationally-exposed individuals appears to induce an increase in systolic and diastolic blood pressure and an increase in the prevalence of hypertension.

Systematic review of the body of evidence for the use of biomarkers in the diagnosis of dementia.

BACKGROUND: Although recent diagnostic criteria for Alzheimer's disease propose the use of biomarkers, validation of these biomarkers by diagnostic test accuracy studies is a necessary first step, followed by the synthesis of the evidence from these studies in systematic reviews and meta-analyses. The quality of the resulting evidence depends on the number and size of the primary studies, their quality, and the adequacy of their reporting. This systematic review assesses the weight and quality of the evidence available from primary diagnostic test accuracy studies. METHODS: A MEDLINE search was performed in August 2011 to identify all potentially relevant publications relating to the biomarkers ß-amyloid, tau, positron emission tomography ((18)F-fluorodeoxyglucose or ligands for amyloid), or magnetic resonance imaging (MRI). The reporting and methodology were assessed using the Standards for Reporting of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies assessment tools, respectively. Because clinical progression to dementia is the most commonly used reference standard, this review focuses on participants with objective cognitive impairment but no dementia at baseline. RESULTS: Of the 19,104 published references identified by the search, 142 longitudinal studies relating to the biomarkers of interest were identified, which included subjects who had objective cognitive impairment but no dementia at baseline. The highest number of studies (n = 70) and of participants (n = 4722) related to structural MRI. MRI also yielded the highest number of studies with extractable data for meta-analysis (n = 32 [46% of all structural MRI studies]), followed by cerebrospinal fluid tau (n = 24 [73%]). There were few studies on positron emission tomography ligands for amyloid having suitable data for meta-analysis (n = 4). There was considerable variation across studies in reporting outcomes, methods of blinding and selection, means of accounting for indeterminate or missing values, the interval between the test and assessments, and the determination of test thresholds. CONCLUSIONS: The body of evidence for biomarkers is not large and is variable across the different types of biomarkers. Important information is missing from many study reports, highlighting the need for standardization of methodology and reporting to improve the rigor of biomarker validation.

Differences between the aging process and the chronic cerebrovascular impairment of memory functioning: the emotional and cognitive interaction.

Three studies illustrate the relationship between memory, emotion, age, and chronic cerebro vascular disorders (CCVDs). In study A, emotion and age interact to produce secondary effects on memory functioning.In study B, emotion-related complaints are correlated with the cognition-related complaints only for high or low lev~ls of impairment For intermediate levels of impairment, the two components of subjective complaints are independent In study C, there is a relationship between aging and the pathological interference by CCVD on memory productivity; young healthy persons do better than aged healthy persons who do better than patients with vascular cognitive impairment (VCI). However,memory processing is different in terms of encoding and organization of stimuli. Young healthy subjects automatically use the semantic structure of the verbal stimuli,whereas the aged healthy persons do so only after a second learning session. Patients with VCI have lost this ability.They keep encoding and organizing items according to the serial effect, the common strategy spontaneously followed by everyone when presented with unstructured stimuli. These are examples of the complex relationships that characterize memory functioning and that should be taken into account when assessing memory when the role of the age factor, the emotional factor, and an eventual CCVD factor should be specifically identified.

Differential characteristics of the aging process and the vascular cognitive impairment in the organization of memory retrieval.

Early identification of cognitive impairment in patients with chronic cerebral vascular disorders can allow for evaluating the time course of the disease up to the phase of conversion to dementia. The specific indicators of pathological cognitive decline should be identifiable vs. the concurrent age-associated changes in memory which accompany the aging process. We propose a method which evaluates memory dysfunctions in vascular cognitive impairment (VCI) as distinct from age-associated memory changes. This method is based on a serial learning task of concrete frequent words and it consists in controlling the effects of age and cerebral pathology on various characteristics of immediate recall, including serial effect and productivity. Ninety participants underwent a between group examination: younger adults vs. older adults vs. VCI patients who were outpatients with a positive history for chronic cerebral vascular disorder, positive neuroimaging examination, a Hachinski ischemic score ≥ 5 and a mild to moderate cognitive impairment. VCI patients show a reduced efficiency of retrieval and recall organization while, age-associated cognitive changes consist of a modification of the serial position effects. In particular, VCI patients, as distinct from same-age normal cases, can perform an only partial utilization of the inherent structure of the memory task with a very limited efficiency of relearning which is not sufficiently supported by the facilitating factors due to task repetition.

Cognitive deficits in schizophrenia: an updated metanalysis of the scientific evidence.

BACKGROUND: This is an update of a previous meta-analysis published in 2005. METHODS: It includes the data published up to march 2010 for a total of 247 papers and 18,300 cases. Cognitive deficits are examined in 5 different domains: Memory functioning (128 studies), Global cognitive functioning (131 studies), Language (70 studies), Executive function (67 studies), Attention (76 studies). Only controlled studies were included: patients vs. normal subjects. RESULTS: Results evidence that in all domains and in all different analyses performed within each domain, patients show a significant reduction of cognitive efficiency with respect to normal subjects. The between studies heterogeneity is very high in almost all domains. There are various sources of this heterogeneity (age, sex, sample size, type of patients, and type of measurement) which contribute to the high degree of not-overlapping information offered by the single studies. CONCLUSIONS: Our results, based on the current scientific evidence, confirm the previous findings that there is a generalized impairment of various cognitive functions in patients with schizophrenia when compared to normal cases. The modalities with which these results are obtained have not changed over the years and the more recent studies do not modify the high heterogeneity previously found between the studies. This reduces the methodological quality of the results. In order to improve the methodological quality of the studies performed in the field of cognitive deficits of patients with schizophrenia, various factors should be taken into account and better managed in designing future studies.

[Depressive symptoms and personality characteristics: phenomenology of affective disorders]. / Sintomi depressivi e caratteristiche di personalità: fenomenologia dei disturbi affettivi.

AIM: Our study aimed to evaluate the relationship between different patterns of symptoms and personality characteristics in a group of 100 patients diagnosed with depression. MATERIALS AND METHOD: The Minnesota Multiphasic Personality Inventory was used as the personality descriptor by the adoption of a multiaxial interpretative technique (Diamond's Axes). These descriptive variables were correlated with the symptoms referred to by the patients and subsequently underwent factor analysis, the method used for the principal components. RESULTS: Four "types" of patients were identified as "different" for symptoms and personality descriptors. In particular, the most important correlations were: anxiety and development of somatic symptoms; low self confidence and autistic behaviour; anger and impulsive behaviour; aggressive behaviour. DISCUSSION: Our results show the relevance of underlying personality characteristics in the presence of depressive symptoms. This relationship seems relevant also for the prediction of likely complications.

[Assessment of simulation and dissimulation in the MMPI-2 test profiles]. / La valutazione della simulazione e della dissimulazione nei profili del test MMPI-2.

UNLABELLED: The aim of this study is to identify the criteria which would allow a differentiation between the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles, obtained from patients who present with problems of minimization of attitude (dissembling) who have shown a minimization of their problems; from patients who answered in a spontaneous and genuine fashion. METHODS: Six hundred and fifty five MMPI profiles of outpatients of the Clinical Psychology Unit, University Hospital, Sapienza University of Rome. Patients were subdivided into two groups, based on the reason for attending: those who submitted voluntarily to a psychodiagnostic assessment and those who were assessed by request of an outside authority, e.g., in the case of those whose driving license was suspended. It has hypothesized that the latter group would not present with problems which would preclude obtaining the benefits required. The variables analyzed were the clinical scale and the validity scale MMPI-2, index F-K and the Ds scale of Gough. On the basis of the values of the F-K index and Ds scale, the patients were reclassified into three simulation categories: spontaneous registration; defended and doubtful's. RESULTS: All indexes, validity scales and clinical scales of the standard profile were found to have significant differences between the "dissimulation" and "normal" groups. Sensibility and specificity of profile classification was according to both indexes 76%. CONCLUSIONS: Current evidence indicates that simulation of pathology is identifiable in MMPI-2 profiles. Our data demonstrate that it is possible to identify case of defensive minimization. These results confirm the hypothesis that simulation is a dimensional characteristic of MMPI which can reach extreme values in both ways: worsening of slight problems or suppression of existing problems.

Therapeutic use of nicergoline.

The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are considered typical symptoms of ergot derivatives. Because of their generally mild and transient nature, treatment discontinuations occur relatively infrequently. The efficacy of nicergoline combined with a favourable safety and tolerability profile at commonly applied doses (60 mg/day) make this agent a valuable therapy in patients with mild to moderate dementia, vascular diseases and balance disorders.

Relationship between memory, attention, and depression in chronic cerebro-vascular patients.

Vascular dementia patients show a component of their impairment as emotional. In the two studies that we present it was possible to illustrate the characteristics of such emotional component. a. The discrepancy between immediate recall and delayed recall appears to be very sensitive to anxiety interference when immediate recall is lower than delayed. b. The presence of emotional problems contributing to memory complaints in VaD patients is not equally distributed along the severity of deterioration dimension but can be identified as a specific component different from the cognitive one especially in that subgroup of patients who present an intermediate level of deterioration.

Citicoline (Cognizin) in the treatment of cognitive impairment.

Pharmacological treatment of cerebrovascular disorders was introduced at the beginning of the 20th Century. Since then, a multitude of studies have focused on the development of a consensus for a well defined taxonomy of these disorders and on the identification of specific patterns of cognitive deficits associated with them, but with no clear consensus. Nevertheless, citicoline has proved to be a valid treatment in patients with a cerebrovascular pathogenesis for memory disorders. A metanalysis performed on the entire database available from the clinical studies performed with this compound confirms the experimental evidence from the animal studies which have repeatedly described the multiple biological actions of citicoline in restoring both the cell lipid structures and some neurotransmitter functions.

A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia.

This review identified 1275 studies examining cognitive deficits in people with schizophrenia, published between 1990 and 2003. Data from 113 studies (4365 patients and 3429 controls) were combined in a meta-analysis carried out on the five cognitive domains of IQ, memory, language, executive function, and attention. Studies were excluded where they lacked a suitable control group or failed to present complete information. In all five cognitive domains, analysis indicated a consistent trend for patients to perform more poorly than healthy controls, with significant heterogeneity across studies. Sources of heterogeneity were analyzed and a need to ensure more appropriate composition of patient and control groups and to adopt a more refined and methodologically correct, hypothesis-driven approach was identified.

History of symptomatic therapy in vascular dementia.

The therapy for vascular dementia has known several changes and updates since the use of niacin in the first years of the 20th century. These modifications were due to the parallel evolution of the concept of vascular dementia. Initially, treatments in this area were proposed because they were considered vasoactive and able to increase the blood flow of the brain. After these, other drugs were introduced because they were also able to ameliorate the oxygen usage by the suffering neurons. The more recent therapeutic proposals were made for drugs active on the metabolic activities of the brain, or with hemorrheological or antioxidant properties. As a consequence, a large array of different pharmacological properties were considered in proposing the several different kinds of drugs as useful in vascular dementia patients. The most recent attempt in this field consists of evaluating the usefulness of traditional antidementia drugs (those with anticholinesterase action) in patients with a prevalence of cerebrovascular disorders.