Factors associated with medication adherence among tuberculosis patients in Timor-Leste

This thesis investigated medication adherence among people living with tuberculosis in Timor Leste. Suboptimal adherence was commonly reported, and was influenced by service inaccessibility, family poverty, patients' absence of disease symptoms and misperception of recovery, untreated depression and a popular cultural belief that luck or chance determines health outcomes. The study has implications for improving health literacy and counselling programs to achieve effective adherence to medication and good health outcomes.

Individual variation in in vitro efficacy of antiplatelet medication - aspirin and clopidogrel

Antiplatelet medication is known to decrease adverse effects in patients with atherothrombotic disease. However, despite ongoing antiplatelet medication considerable number of patients suffer from atherothrombotic events. The aims of the study were 1) to evaluate the individual variability in platelet functions and compare the usability of different methods in detecting it, 2) to assess variability in efficacy of antiplatelet medication with aspirin (acetylsalicylic acid) or the combination of aspirin and clopidogrel and 3) to investigate the main genetic and clinical variables as well as potential underlying mechanisms of variability in efficacy of antiplatelet medication. In comparisons of different platelet function tests in 19 healthy individuals PFA-100® correlated with traditional methods of measuring platelet function and was thus considered appropriate for testing individual variability in platelet activity. Efficacy of ongoing 100mg aspirin daily was studied in 101 patients with coronary artery disease (CAD). Aspirin response was measured with arachidonic acid (AA)-induced platelet aggregation, which reflects cyclo-oxygenase (COX)-1 dependent thromboxane (Tx) A2 formation, and PFA-100®, which evaluates platelet activation under high shear stress in the presence of collagen and epinephrine. Five percent of patients failed to show inhibition of AA-aggregation and 21% of patients had normal PFA-100® results despite aspirin and were thus considered non-responders to aspirin. Interestingly, the two methods of assessing aspirin efficacy, platelet aggregation and PFA-100®, detected different populations as being aspirin non-responders. It could be postulated that PFA-100® actually measures enhanced platelet function, which is not directly associated with TxA2 inhibition exerted by aspirin. Clopidogrel efficacy was assessed in 50 patients who received a 300mg loading dose of clopidogrel 2.5 h prior to percutaneous coronary intervention (PCI) and in 51 patients who were given a loading dose of 300mg combined with a five day treatment of 75mg clopidogrel daily mimicking ongoing treatment. Clopidogrel response was assessed with ADP-induced aggregations, due to its mechanism of action as an inhibitor of ADP-induced activation. When patients received only a loading dose of clopidogrel prior to PCI, 40% did not gain measurable inhibition of their ADP-induced platelet activity (inhibition of 10% or less). Prolongation of treatment so that all patients had reached a plateau of inhibition exerted by clopidogrel, decreased the incidence of non-responders to 20%. Polymorphisms of COX-1 and GP VI, as well as diabetes and female gender, were associated with decreased in vitro aspirin efficacy. Diabetes also impaired the in vitro efficacy of short-term clopidogrel. Decreased response to clopidogrel was associated with limited inhibition by ARMX, an antagonist of P2Y12-receptor, suggesting the reason for clopidogrel resistance to be receptor-dependent. Conclusions: Considerable numbers of CAD patients were non-responders either to aspirin, clopidogrel or both. In the future, platelet function tests may be helpful to individually select effective and safe antiplatelet medication for these patients.

Electroencephalographic and Immunological Findings in Patients with Schizophrenia Treated with Clozapine

This work studies the effect of clozapine (CLO) on the electroencephalography (EEG) and reactive oxygen species (ROS) production by peripheral blood monocytes (MO) in patients with schizophrenia (SCH). The aim of the study was to investigate the mechanism of action of CLO, to clarify the effect of CLO on EEG absolute power spectrum and ROS production, and explore the relationship of these effects with clinical response. We also tried to clarify whether the EEG changes or ROS production would help to identify the patients who were most likely to respond to treatment with CLO. Our findings suggest that the amount of slow background activity, particularly the absolute power of the theta frequency band, in the EEG is markedly increased by CLO treatment and this finding correlates positively with clinical improvement in patients with SCH. CLO affected the production of ROS by blood MO with reduction or minimal increase of the ROS production being associated with clinical improvement, whereas marked increase of the ROS production did not. Also a positive correlation between theta absolute power increase in the EEG and suppression of the production of ROS by blood MO was found. The correlations between different symptom clusters of SCH and the EEG rhythms were investigated; the absolute power of beta activity in the EEG seemed to correlate positively to overall psychopathology in patients with SCH showing inadequate response. The results suggest that the EEG background activity and investigation of the production of ROS by MO seem to be an adjunctive method to objectively assess and possibly predict the therapeutic effect of CLO in patients with chronic SCH showing inadequate response to treatment with conventional antipsychotics.

Functional limitations and quality of life in schizophrenia and other psychotic disorders

There is substantial evidence of the decreased functional capacity, especially everyday functioning, of people with psychotic disorder in clinical settings, but little research about it in the general population. The aim of the present study was to provide information on the magnitude of functional capacity problems in persons with psychotic disorder compared with the general population. It estimated the prevalence and severity of limitations in vision, mobility, everyday functioning and quality of life of persons with psychotic disorder in the Finnish population and determined the factors affecting them. This study is based on the Health 2000 Survey, which is a nationally representative survey of 8028 Finns aged 30 and older. The psychotic diagnoses of the participants were assessed in the Psychoses of Finland survey, a substudy of Health 2000. The everyday functioning of people with schizophrenia is studied widely, but one important factor, mobility has been neglected. Persons with schizophrenia and other non-affective psychotic disorders, but not affective psychoses had a significantly increased risk of having both self-reported and test-based mobility limitations as well as weak handgrip strength. Schizophrenia was associated independently with mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Another significant factor associated with problems in everyday functioning in participants with schizophrenia was reduced visual acuity. Their vision was examined significantly less often during the five years before the visual acuity measurement than the general population. In general, persons with schizophrenia and other non-affective psychotic disorder had significantly more limitations in everyday functioning, deficits in verbal fluency and in memory than the general population. More severe negative symptoms, depression, older age, verbal memory deficits, worse expressive speech and reduced distance vision were associated with limitations in everyday functioning. Of all the psychotic disorders, schizoaffective disorder was associated with the largest losses of quality of life, and bipolar I disorder with equal or smaller losses than schizophrenia. However, the subjective loss of qualify of life associated with psychotic disorders may be smaller than objective disability, which warrants attention. Depressive symptoms were the most important determinant of poor quality of life in all psychotic disorders. In conclusion, subjects with psychotic disorders need regular somatic health monitoring. Also, health care workers should evaluate the overall quality of life and depression of subjects with psychotic disorders in order to provide them with the basic necessities of life.

A Study of Long-range Correlations in Schizophrenia EEG using Detrended Fluctuation Analysis

In this paper, we have studied electroencephalogram (EEG) activity of schizophrenia patients, in resting eyes closed condition, with detrended fluctuation analysis (DFA). The DFA gives information about scaling and long-range correlations in time series. We computed DFA exponents from 30 scalp locations of 18 male neuroleptic-naIve, recent-onset schizophrenia (NRS) subjects and 15 healthy male control subjects. Our results have shown two scaling regions in all the scalp locations in all the subjects, with different slopes, corresponding to two scaling exponents. No significant differences between the groups were found with first scaling exponent (short-range). However, the second scaling exponent (long-range) were significantly lower in control subjects at all scalp locations (p<0.05, Kruskal-Wallis test). These findings suggest that the long-range scaling behavior of EEG is sensitive to schizophrenia, and this may provide an additional insight into the brain dysfunction in schizophrenia.

Investigational drugs for schizophrenia targeting the dopamine receptor: phase II trials

Introduction: For over half a century now, the dopamine hypothesis has provided the most widely accepted heuristic model linking pathophysiology and treatment in schizophrenia. Despite dopaminergic drugs being available for six decades, this system continues to represent a key target in schizophrenia drug discovery. The present article reviews the scientific rationale for dopaminergic medications historically and the shift in our thinking since, which is clearly reflected in the investigational drugs detailed. Areas covered: We searched for investigational drugs using the key words `dopamine,' `schizophrenia,' and `Phase II' in American and European clinical trial registers (clinicaltrials. gov; clinicaltrialsregister.eu), published articles using National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. We provide a brief description of drugs targeting dopamine synthesis, release or metabolism, and receptors (agonists/partial agonists/antagonists). Expert opinion: There are prominent shifts in how we presently conceptualize schizophrenia and its treatment. Current efforts are not as much focused on developing better antipsychotics but, instead, on treatments that can improve other symptom domains, in particular cognitive and negative. This new era in the pharmacotherapy of schizophrenia moves us away from the older `magic bullet' approach toward a strategy fostering polypharmacy and a more individualized approach shaped by the individual's specific symptom profile.

Targeting the dopamine receptor in schizophrenia: investigational drugs in Phase III trials

Introduction: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon after, it was established that blockade of dopamine and, in particular, the D-2 receptor was central to this effect. Dopamine continues to represent a critical line of investigation, although much of the work now focuses on its potential in other symptom domains. Areas covered: A search was carried out for investigational drugs using the key words `dopamine', `schizophrenia' and `Phase III' in an American clinical trial registry (clinicaltrials.gov), published articles using the National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. Drugs were excluded that were already FDA approved. Expert opinion: There remains interest, albeit diminished, in developing better antipsychotic compounds. The greatest enthusiasm currently centres on dopamine's role in negative and cognitive symptom domains. With theories conceptualising hypodopaminergic activity as underlying these deficits, considerable effort is focused on drug strategies that will enhance dopamine activity. Finally, a small body of research is investigating dopaminergic compounds vis-a-vis side-effect treatments. In domains beyond psychosis, however, dopamine arguably is not seen as so central, reflected in considerable research following other lines of investigation.

Selective Review of Proton Magnetic Resonance Spectroscopy in Schizophrenia

Magnetic Resonance Spectroscopy (MRS) offers a unique opportunity to measure brain metabolites in-vivo, and in doing so enables one to understand the brain function and cellular processes implicated in the pathophysiology of psychiatric disorders. MRS, in addition to being non-invasive, is devoid of radioactive tracers and ionizing radiation, a distinct advantage over other imaging modalities like positron emission tomography and single photon emission computed tomography. With advances in MRS technique it is now possible to quantify concentrations of relevant compounds like neurotransmitters, neuronal viability markers and pharmacological compounds. Majority of the MRS studies have examined the neurometabolites in schizophrenia, a common and debilitating psychiatric disorder. Abnormalities in N Acetyl aspartate and Glutamate are consistently reported while the reports regarding the myoinsoitol and choline are inconsistent. These abnormalities are not changed across the illness stages and despite treatment. However, multiple technical challenges have limited the widespread use of MRS in psychiatric disorders. Guidelines for uniform acquisition and preprocessing are need of the hour, which. would increase the replicability and validity of MRS measures in psychiatry. Finally long term, prospective, longitudinal studies are required in different psychiatric disorders for potential clinical applications.

Prevalence and clinical correlates of obsessive-compulsive disorder in schizophrenia

Obsessive compulsive symptoms frequently occur in a substantial proportion of patients with schizophrenia. The term schizoobsessive has been proposed to delineate this subgroup of schizophrenia patients who present with obsessive compulsive symptoms/disorder. However, whether this co-occurrence is more than just co-morbidity and represents a distinct subgroup remains controversial. A striking variation is noted across studies examining prevalence of obsessive compulsive symptoms/disorder in schizophrenia patients and their impact on clinical profile of schizophrenia. Hence, in this study, we examined the prevalence of obsessive compulsive symptoms/disorder in a large sample of consecutively hospitalized schizophrenia patients and compared the clinical and functional characteristics of schizophrenia patients with and without obsessive compulsive symptoms/disorder. We evaluated 200 consecutive subjects with the DSM-IV diagnosis of schizophrenia using the Structured Clinical Interview for DSM-IV Axis I disorders, Positive and Negative Syndrome Scale, Yale Brown Obsessive Compulsive Scale, Brown Assessment of Beliefs Scale, Clinical Global Impression-Severity scale, Global Assessment of Functioning Scale, Family Interview for Genetic Studies and World Health Organization Quality of Life scale. The prevalence of obsessive compulsive symptoms in patients with schizophrenia was 24% (n = 48); 37 of them had obsessive compulsive disorder (OCD) and II had obsessive compulsive symptoms not amounting to a clinical diagnosis of OCD (OCS). Schizophrenia patients with OCS/OCD had an earlier age at onset of schizophrenia symptoms, lower positive symptoms score, higher co-morbidity with Axis II disorders, higher occurrence of OCD in family and better quality of life. Findings of the study indicate a higher prevalence of OCS/OCD in schizophrenia. Schizophrenia patients with and without OCS/OCD have comparable clinical profile with few exceptions. High rates of OCD in first degree relatives suggest possible genetic contributions and differences in neurobiology. Finally, evidence to consider schizoobsessive as a distinct diagnostic entity is inconclusive and warrants further studies. (C) 2014 Elsevier Inc. All rights reserved.