Real-world effectiveness of long acting aripiprazole: Treatment persistence and its correlates in the Italian clinical practice.

OBJECTIVES: To identify the variables that are associated with persistence to Aripiprazole-Long Acting (A-LAI), in adult patients with schizophrenia. METHODS: Observational, retrospective, non-interventional study involving 261 patients with schizophrenia. RESULTS: Eighty-six percent of study subjects were persistent for at least 6 months. All subjects with baseline CGI-S of 1 or 2, 95% of subjects with CGI-S of 3, 86% with CGI-S of 4, 82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7 were persistent. A-LAI treatment continuation rate was higher in patients with: 1) baseline CGI score ≤ 4; 2) schizophrenia dimension (LDPS) mania score ≤ 5; 3) psychotic spectrum schizoid score ≤ 11. CONCLUSIONS: A relatively high number of patients (n = 225, 86%) were persistent to A-LAI for at least 6 months. Not surprisingly, very severe patients were more unlikely to be persistent. However, it is noteworthy that a large number of subjects with high CGI score at the time when A-LAI was started (82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7) were persistent. Larger, controlled, prospective and longer studies are warranted.

Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

The "Social-mobile autopsy": The evolution of psychological autopsy with new technologies in forensic investigations on suicide.

Suicide is a huge deal in general public health, representing the second cause of mortality in young people worldwide. The suicidal setting analysis is usually performed through psychological autopsy, a method of investigation commonly used to study what leads to suicide. Psychological autopsy, though, requires the involvement of family and friends, or the finding of a diary or a suicide note. Nowadays, this is not always possible, especially during adolescence, the more if we consider new categories of people that are more used to live in a web dimension, than in a real one. So, with the advent of a new kind of social system including the web, psychological autopsy, as we know it, is not enough to determine the setting of an event. We here report the case of a 17-year old girl who committed suicide by hanging down from her house, leaving no suicide note. We propose a new investigation method developed through the analysis of phone messages and Facebook profile in order to better reconstruct the event. Although the standing difficulties in reconsidering the intimate motivations leading to such a decision, psychological autopsy nowadays needs to consider also social networks in order to prevent similar situations and even reconstruct the psychological dimension of the fact. We propose a model of Social-mobile autopsy.

Perceived insecurity, mental health and urbanization: Results from a multicentric study.

AIMS: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in 'big cities' can influence the levels of patients' perceived insecurity and social contacts compared to living in a non-urbanized context. METHODS: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. RESULTS: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. CONCLUSION: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients' psychological and physical well-being, contributing to high levels of distress.

Estimating the Impact of Workplace Bullying: Humanistic and Economic Burden among Workers with Chronic Medical Conditions.

BACKGROUND: Although the prevalence of work-limiting diseases is increasing, the interplay between occupational exposures and chronic medical conditions remains largely uncharacterized. Research has shown the detrimental effects of workplace bullying but very little is known about the humanistic and productivity cost in victims with chronic illnesses. We sought to assess work productivity losses and health disutility associated with bullying among subjects with chronic medical conditions. METHODS: Participants (N = 1717) with chronic diseases answered a self-administered survey including sociodemographic and clinical data, workplace bullying experience, the SF-12 questionnaire, and the Work Productivity Activity Impairment questionnaire. RESULTS: The prevalence of significant impairment was higher among victims of workplace bullying as compared to nonvictims (SF-12 PCS: 55.5% versus 67.9%, p < 0.01; SF-12 MCS: 59.4% versus 74.3%, p < 0.01). The adjusted marginal overall productivity cost of workplace bullying ranged from 13.9% to 17.4%, corresponding to Italian Purchase Power Parity (PPP) 2010 US$ 4182-5236 yearly. Association estimates were independent and not moderated by concurrent medical conditions. CONCLUSIONS: Our findings demonstrate that the burden on workers' quality of life and productivity associated with workplace bullying is substantial. This study provides key data to inform policy-making and prioritize occupational health interventions.

Disordered eating behavior and mental health correlates among treatment seeking obese women.

BACKGROUND AND OBJECTIVES: Previous research has suggest that obesity is associated with increased risk for psychopathological disorders, however, little is known about which obese patients are most vulnerable to psychopathological disorders. We therefore investigated 126 treatment-seeking obese women to describe eating disorder pathology and mental health correlates, and to identify disordered eating behaviors that may place obese at increased risk for psychopathological disorders. MATERIALS AND METHODS: The Structured Clinical Interview for DSM-IV (SCID) was used to identify Eating Disorders (ED). A battery of psychological tests, including the Anxiety Scale Questionnaire (ASQ,) Clinical Depression Questionnaire (CDQ), Eating Disorder Inventory-2 (EDI-2) Eating Attitudes Test-26 (EAT-26) scales and structured clinical interview were administered to all the patients. We analyzed the link between psychopathological disorders and eating attitudes by using both multiple regression analysis and non-parametric correlation. RESULTS: Disordered eating behaviors and emotional behavioral aspects related to Anorexia Nervosa, such as ineffectiveness, are strongly linked to the depression and anxiety in obese subjects. No correlation was found between psychopathological disorders and age or anthropometric measurements. CONCLUSIONS: Findings corroborate earlier work indicating that psychological distress is elevated in obese treatment seeking, bolstering the need for mental health assessment of such individuals. The feeling of ineffectiveness constitutes the major predictor of psychopathological aspects. This is an important result which may inform the development of effective interventions for obese patients and prevention of psychopathological disorders.

Orthorexia nervosa: a frequent eating disordered behavior in athletes.

Striving for enhancing athletic performance, many sportsmen undergo rigid dietary habits, which could lead to eating disorders (EDs) or Orthorexia Nervosa (ON), a psychopathological condition characterized by the obsession for high quality food. The aim of the study was to examine the occurrence of ON in athletes and to verify the relationship between ON and EDs. Five-hundred-seventy-seven athletes and 217 matched controls were administered the following tests: ORTO-15, Eating Attitude Test 26 (EAT-26), Body Uneasiness Test (BUT) and Yale-Brown-Cornell Eating Disorder Scale (YBC-EDS). High positivity to ORTO-15 (28%) and EAT-26 (14%) emerged in athletes, whereas a high rate of BUT positivity was evident among controls (21%). Multivariate logistic regression analysis revealed that independent predictors of ON are previous dieting, age, positivity to YBC-EDS, positivity to EAT-26, competition level, and number of YBC-EDS preoccupations and rituals. Sharing many features with both EDs and Obsessive-Compulsive Spectrum, ON represents a crossroad between these pathologic conditions and might compromise the health state of an athlete. Therefore, coaches should consider important to detect symptoms of EDs and ON in their athletes.

The development and validation of the Body Image Dimensional Assessment (BIDA).

AIM: To validate a silhouette-based scale, the Body Image Dimensional Assessment (BIDA), an instrument for the screening of body dissatisfaction in large samples. MATERIALS AND METHODS: Five-hundred ninety-two both gender non-clinical participants and 57 patients with eating disorders (ED) were administered the BIDA and the Body Dissatisfaction subscale of the Eating Disorder Inventory 2 (BD-EDI2). The BIDA consists of only 4 items to answer with reference to a series of four silhouettes not age- nor gender-related using a numeric scale that allows the quantification of the degree of Body Dissatisfaction, Sexual Body Dissatisfaction, Comparative Body Dissatisfaction and the calculation of the final Body Dissatisfaction Index (BDI). RESULTS AND CONCLUSIONS: The study has shown that the BIDA has good reliability and validity as well as high predictive capability at a threshold BDI≥30 (sensitivity = 83.3% and specificity = 92.1%). By virtue of the rapid timing of administration, the BIDA can be a useful screening instrument of body dissatisfaction in non clinical populations to detect people at risk for ED and a follow-up instrument in clinical setting.

Anticholinergic drug-induced delirium in an elderly Alzheimer's dementia patient.

Drug-induced delirium is a common matter in the elderly and anticholinergics, together with a number of different drugs, may significantly contribute to the delirium onset, especially in demented people. We report a case of a probable anticholinergic drug-induced delirium in an elderly patient. An 80-year-old man with Alzheimer's dementia presented with wandering, depressed mood with crying, somatic worries, anedonism and suicide recurrent ideas. A first external psychiatric assessment led to the diagnosis of melancholic depression and therapy with haloperidol 2mg/day, orphenadrine 100mg daily, amitriptyline 40 mg/day, lorazepam 2mg/day was started. Two weeks later patient suddenly developed delirium, characterized by nocturnal agitation, severe insomnia, daytime sedation, confusion, hallucinations and persecutory delusions. These symptoms progressively worsened, with the consequent caregiver's stress. A geriatric consultation excluded the main causes of delirium, therefore both Operative Units of Pharmacovigilance and Psychiatry were activated, for a clinical pharmacological and psychiatric assessment. Haloperidol, amitriptyline and orphenadrine were promptly dismissed. The patient began a treatment with quetiapine 25mg/day for two days, then twice a day, and infusion of saline 1000 ml/day for two days; psychiatric symptoms gradually diminished and therapy with galantamine was begun. We postulate that this clinical report is suggestive for an anticholinergic drug- induced delirium since the Naranjo probability scale indicated a probable relationship between delirium and drug therapy. In conclusion, a complete geriatric, pharmacological, and psychiatric evaluation might be necessary in order to reduce the adverse drug reactions in older patients treated with many drugs.

Demineralizing action of EGTA in endodontics.

The demineralization of dentin obtained by treatment with a chelating agent ethylene diamminotetracetic acid (EDTA) or ethylene glycol-bis(beta-aminoethyl ether)-N-tetraacetic acid (EGTA), is a dynamic process involving chelation and solubilization. The actions of the EDTA and EGTA on dentin are influenced by the pH. Increasing mM concentrations of EDTA or EGTA the equivalent pH decreases in a similar slope to 80 mM chelator concentration. Increasing the chelator concentration different data were obtained: with EGTA the pH decreases slightly while with EDTA goes back up to the initial values. After 80 mM, EDTA reduces the activity on the dentin, and EGTA continues to work at higher concentrations. We demonstrated that EGTA solubilized more of 60 percent of dentin while EDTA gives about 20% at the maximal of the solubility.

Generalised urticaria in a young woman treated with clomipramine and after ingestion of codfish.

We report a case of generalized dermatitis and itch induced by a possible drug-food interaction in a young woman who was consuming clomipramine for Obsessive Compulsive Disorder (OCD). A 33-year-old woman affected by anxiety symptoms presented to our observation for a clinical evaluation. After psychiatric evaluation, the diagnosis of OCD was performed according to DSM-IV-TR and a pharmacological treatment with clomipramine (75-100 mg/day) plus alprazolam (0.5 mg/day) was started. About one month later, the patient developed a severe generalized urticaria with intense itch. A new anamnesis revealed that on the day before the development of the skin rash, no other drug was consumed and the patient had eaten codfish; clomipramine was then gradually discontinued and changed into paroxetine (30 mg/day). At the moment the patient does not show any OCD related symptom and any adverse event to paroxetine treatment has been recorded. We postulate a possible interaction between clomipramine and codfish ingestion. Allergic potential of clomipramine was investigated, while clomipramine de-challenge induced a decrease of the skin rash, the drug re-challenge performed one month later did not induce any adverse event. In contrast, when the combined re-challenge of codfish and clomipramine was performed urticaria was newly observed. The Naranjo Probability Scale Score suggested a probable causal relationship between drug-food interaction and the skin rash. In conclusion, we suggest evaluating also the complete risk of drug-food interaction occurring on clomipramine treatment.

Nitric oxide synthase in healthy and inflamed human dental pulp.

Nitric oxide synthase (NOS) plays a significant role in the pathogenesis of pulpitis. In this study, we hypothesized the existence of endothelial (eNOS) and inducible (iNOS) enzyme isoforms in human dental pulp. Extracted third molar pulps were divided into groups based on clinical diagnosis: healthy, hyperemic, and irreversible pulpitis. We have localized the eNOS and iNOS by immunohistochemistry and have tested their mRNA expression by RT-PCR and protein levels by Western blots. eNOS is present in the endothelial cells and odontoblasts of the healthy pulp, but an elevation of eNOS mRNA and protein levels with a concomitant dilation of vessels was characteristic under pathological conditions. Healthy pulp tissue failed to exhibit any iNOS; however, acute inflammation enhanced the mRNA and protein levels of iNOS, mainly in the leukocytes. There are differences in localization and expression between eNOS and iNOS in healthy and inflamed dental pulp.

[In vitro antimicrobial activity of glutaraldehyde plus O-phenylphenol association (ratio 2:1)]. / Attività antimicrobica in vitro dell'associazione tra glutaraldeide e ofenilfenolo (ratio 2:1).

BACKGROUND: The correct use of antiseptics, disinfectants and sterilization processes to inactivate or remove micro-organisms is an essential component of an effective infection control program. To reach this result the use of phenolic detergent-disinfectants which work well as a presoak has always been suggested in lieu of sterilization involving submerging instruments in a properly prepared glutaraldehyde solution for about 6 to 10 hrs. This study investigated the in vitro effectiveness of disinfectant solution containing 2% glutaraldehyde and 1% o-phenylphenol. METHODS: The organisms used were purchased from the American Type Culture Collection (Escherichia coli ATCC 25922, Candida albicans ATCC 10231, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228), and from our clinical collection (Proteus mirabilis CH 14, Klebsiella oxytoca CH 22, Serratia liquefaciens CH 90). MIC and MBC were evaluated as testing solution for antimicrobial activity. The contact time studied between disinfectant and bacteria were 30 sec, 1, 2, 5, 10, 20 and 30 min. RESULTS: The results showed that MIC values for most bacteria were 3.75 mg/ml. The MBC values were similar or higher than the MIC. The disinfectant solution killed E. coli and C. albicans already after 10 min, but for S. aureus 30 min was necessary. CONCLUSIONS: This study proved that this solution attained the sterilization of surgical instruments in good timing and at low cost.

How to improve digital dental radiograph reproducibility: an individualized technique.

Today, the advantages of the use of digital dental radiography as a valid alternative to conventional techniques are well known. In clinical dental practice, it can be useful to realize intraoral dental x-rays that can be compared, even after some years. The use of a conventional XCP instrument with the "long cone" technique helps to limit image distortion, but the comparison is poor. Moreover, in digital radiography, obtaining almost identical images is essential to superimpose them with dedicated software. The aim of the present work was to obtain fully superimposable and reproducible intraoral digital images through the use of an individual resin positioner. The laboratory phases are all described to create a system that enables exact placement of the digital sensor SIDEXIS (Sirona, Germany) in the mouth of the patient. The authors present a case report where the described technique is applied in the orthodontic field to evaluate molar distalization with a fixed appliance.

Root canal treatment in mandibular canines with two roots: a report of two cases.

AIM: To highlight anatomical variation in the mandibular canine. SUMMARY: Two clinical case reports are presented to illustrate anatomical variation in the human mandibular canine. Endodontic treatment may sometimes fail because morphological features of the tooth adversely affect the treatment procedures. Many investigators have reported the anatomical variations associated with mandibular canines. Mandibular canines are recognized as usually having one root and one root canal in most cases, although approximately 15% may have two canals or sometimes two roots. This paper describes two clinical cases of mandibular canines with two roots and two canals. KEY LEARNING POINTS: Failure to control infection in the root canal system has an adverse impact on outcome. Clinicians should be aware of anatomical variations in the teeth they are managing, and should never assume that canal systems are simple. The majority of mandibular canines have one root and root canal, but 15% may have two canals, and a smaller number may have two distinct roots.

RB2/p130 gene-enhanced expression down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo.

Angiogenesis is an essential step in the progression of tumor formation and development. The switch to an angiogenetic phenotype can occur as a distinct step before progression to a neoplastic phenotype and is linked to genetic changes such as mutations in key cell cycle regulatory genes. The pathogenesis of the angiogenetic phenotype may involve the inactivation of tumor suppressor genes such as the "guardian of the genome," p53, and the cyclin-dependent kinase inhibitor p16. Retinoblastoma family member RB2/p130 encodes a cell cycle regulatory protein and has been found mutated in different tumor types. Overexpression of RB2/p130 not only suppresses tumor formation in nude mice but also causes regression of established tumor grafts, suggesting that RB2/p130 may modulate the angiogenetic balance. We found that induction of RB2/p130 expression using a tetracycline-regulated gene expression system as well as retroviral and adenoviral-mediated gene delivery inhibited angiogenesis in vivo. This correlated with pRb2/p130-mediated down-regulation of vascular endothelial growth factor protein expression both in vitro and in vivo.

Nuclear matrix provides linkage sites for translocated NF-kappa B: morphological evidence.

In response to the binding of extracellular ligands to cell surface receptors, multiple transcription factors are activated in the cytoplasm and translocated into the nucleus where they exert positive or negative control over cellular genes. The human transcription factor NF-kappa B family regulates the expression of a large number of genes involved in the host defence mechanism. They are typically present in the cytoplasm bound to the inhibitory I kappa B proteins. The activation of NF-kappa B involves the signal-induced degradation of these proteins, allowing NF-kappa B to translocate to the nucleus. In this study, by multiparametric analysis, we recognise in RPMI-8402 DMSO-activated cells the intracellular movement of transcription factor NF-kappa B providing its definite intranuclear collocation. Intact cells, purified nuclei and nuclear matrix preparations after 4 h of treatment were processed for morphological and biochemical analyses. Light and electron microscope observations show, in untreated cells, the presence of NF-kappa B protein homogeneously retained in the cytoplasm. Treated cells display a massive presence of NF-kappa B at the nuclear level bound to the interchromatin region. Immunoblotting of the same specimens confirms the strong association of NF-kappa B with the nuclear scaffold. Taken together, the data presented in this manuscript support a model where DMSO treatment provokes the cleavage and translocation of NF-kappa B from the cytoplasm to the nucleus and, in particular, in the proteinaceous network of the nuclear matrix sustaining the active role of this subcellular structure on regulation of eukaryotic gene expression.

Conventional and new antidepressant drugs in the elderly.

Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and nonsuicide mortality. Therefore, it is very important to make an early diagnosis and a suitable pharmacological treatment, not only for resolving the acute episode, but also for preventing relapse and enhancing the quality of life. Age-related changes in pharmacokinetics and in pharmacodynamics have to be kept into account before prescribing an antidepressant therapy in an old patient. In this paper some of the most important and tolerated drugs in the elderly are reviewed. Tricyclic antidepressants have to be used carefully for their important side effects. Nortriptyline, amytriptiline, clomipramine and desipramine as well, seem to be the best tolerated tricyclics in old people. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose and include the so called atypicals, such as selective serotonin reuptake inhibitors, serotonin noradrenalene reuptake inhibitors and noradrenaline reuptake inhibitors. Monoamine oxidase (MAO) inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy; the last generation drugs (reversible MAO inhibitors), such as meclobemide, seem to be very successful. Mood stabilizing drugs are widely used for preventing recurrences of depression and for preventing and treating bipolar illness. They include lithium, which is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients for its side effects, the anticonvulsants carbamazepine and valproic acid. Putative last generation mood stabilizing drugs include the dihydropyridine L-type calcium channel blockers and the anticonvulsants phenytoin, lamotrigine, gabapentin and topiramate, which have unique mechanisms of action and also merit further systematic study. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide or drug resistant forms.

Localization of the e-NOS enzyme in endothelial cells and odontoblasts of healthy human dental pulp.

Nitric oxide synthases (NOS) are important enzymes present in different cells such as endothelial cells, macrophages, etc. Recently, it has been found that nitric oxide (NO) is responsible for vasodilation, blood pressure regulation, platelet aggregation, cardiac contractility, and the mediation of immunity during bacterial infections and inflammation. However, the production and role of NO in various structures of the oral cavity have not been investigated extensively. The aim of this study was to evaluate the presence of e-NOS in healthy human odontoblasts and endothelial cells of the dental pulp. Twenty healthy human dental pulps were collected and frozen and pulp slices were obtained using a cryostat. The e-NOS enzyme was revealed by immunohistochemical analysis and the enzyme level was detected by Western blotting and mRNA expression by RT-PCR. The immunohistochemical results demonstrated, for the first time, the presence of e-NOS in odontoblasts and in endothelial cells. The presence of e-NOS m-RNA was confirmed by RT-PCR and the expression of the protein by Western blotting. These results clearly show that the e-NOS enzyme is present in both odontoblasts and endothelial cells of healthy human pulp. The presence of e-NOS in the odontoblast and endothelial cells of the dental pulp may mediate local vasodilation and cell proliferation.