Origin oriented management of inverted papilloma of the frontal sinus.

BACKGROUND: Despite the great progress in endoscopic management of inverted papilloma (IP), involvement of the frontal sinus (FS) remains a challenge. METHODOLOGY: Six cases of FS IP were assessed. Extent of surgery included simple frontal recess clearance, extended frontal sinusotomy, and modified Lothrop approach. There was no need for adjuvant frontal trephination or an external osteoplastic flap. RESULTS: FS involvement was observed in 6 out of 119 cases of IP (5%). In one case, IP was originating from the FS and in four it was extending to the FS. The sixth case had a wide origin from the anterior ethmoid and FS. Complete resection of FS IP was achieved in all cases with a single incidence of CSF leak. No recurrence was identified after a follow-up period of an average of 27 months. CONCLUSIONS: FS IP originating outside FS can be delivered transnasally with or without frontal ostium widening and preserving FS mucosa and bone. Inverted papillomata originating from FS proper and those with origin from inside and outside the FS can also be resected tranasnasally after widening of the frontal ostium with removal of surrounding mucosa and drilling or curettage of underlying bone at attachment sites.

Dysglycemia in a community sample of people treated for schizophrenia: the Diabetes in Schizophrenia in Central-South Ontario (DiSCO) study.

OBJECTIVE: Despite increasing recognition of schizophrenia as a risk factor for diabetes, the prevalence and correlates of dysglycemia in people with schizophrenia have not been adequately studied. Discerning the modifiable risk factors is crucial for developing diabetes prevention strategies in schizophrenia. METHODS: Socio-demographic, clinical and recent laboratory data were compiled from the case records and supplemental sources of 1123 people treated for schizophrenia who were living across five different communities in the region. RESULTS: Screening rates for fasting plasma glucose (FPG) varied between 63-100% across the five communities, while other metabolic indices were monitored less frequently. 39 subjects (3.5%) in the sample had an existing diagnosis of type 2 diabetes. Among the others, 845 (78%) had FPG measured in the preceding 6 months, with the following results: FPG < or = 5.6 mmol/l in 474 (56%), 5.6-6.9 mmol/l in 268 (31%), and > or = 7 mmol/l in 103 (12.2%) subjects. Dysglycemia (FPG > or = 5.6 mmol/l) was significantly associated with older age (odds ratio [OR] 1.031), longer duration of schizophrenia (OR 1.062), self reported family history of diabetes (OR 8.87), body mass index (OR 1.081), excess weight (OR 1.014) and independent living status (OR 1.779), while European ethnicity (OR 0.706) and regular physical activity (OR 0.958) lowered the risk. No statistically significant correlations were noted with gender, level of education or functioning, or the type of antipsychotic drug prescribed. CONCLUSIONS: There was a two-fold increase in the prevalence of dysglycemia, while there was a substantial under-recognition of and intervention for, diabetes and pre-diabetes in this sample of people treated for schizophrenia.

Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine.

BACKGROUND: Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure. OBJECTIVES: The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia. METHODS: In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI). RESULTS: Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life. CONCLUSIONS: Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities.

Brain imaging research on subjective responses to psychotropic drugs.

OBJECTIVE: Neuroimaging studies on subjective responses to psychotropic drugs in humans were reviewed to examine progress in the field and identify gaps in knowledge. METHOD: An exhaustive search of computerized databases identified two categories of in vivo imaging studies: i) correlates of negative(dysphoric) subjective responses to neuroleptic use in schizophrenia, and ii) research on positive (euphoric) subjective responses, mostly from substance abuse population. RESULTS: Research has been largely confined to neurochemical imaging of dopamine in the striatal complex, confirming earlier speculations that impaired or deficient dopaminergic function is associated with dysphoric responses, and enhanced activity is associated with euphoric or pleasurable responses. Cerebral blood flow, regional metabolic rate and glucose utilization studies provided preliminary clues to the putative neuroanatomical sites. CONCLUSION: Neuroimaging techniques added credibility to the study of subjective responses; however, further studies are required to identify the underlying anatomical and neurochemical interactions in order to enhance their applied value.

Neuroleptic dysphoria: revisiting the concept 50 years later.

OBJECTIVE: To review the concept of neuroleptic dysphoria, its historical development and the current state of the art. METHOD: This paper is based on extensive but selective literature review and also draws on our extensive clinical and research experiences. RESULTS: Although the construct of neuroleptic dysphoria was recognized shortly following the introduction of the first antipsychotic, chlorpromazine, it took several years for the concept to receive adequate research and clinical attention. Without having direct evidence to link neuroleptic dysphoria to dopamine, it was generally understood that dopamine played a significant role in its genesis. In recent neuroimaging studies and dopamine depletion strategies, the role of dopamine in the genesis of neuroleptic dysphoria has been directly confirmed. CONCLUSION: Neuroleptic dysphoria is a valid construct, which has significant implications for treatment and outcome. It is now clear that it relates to dopamine activities in the nigrostriatal complex. Recent research has also raised the issue of whether neuroleptic dysphoria is a variant of extrapyramidal symptoms. Meanwhile, the role of dopamine in both the genesis of neuroleptic dysphoria and addictive behaviour has raised the issue of both conditions being different facets of the schizophrenic disease process. The recent interface of addiction and psychiatry research may have opened a new science: the science of subjective tolerability disorders.

Neuroleptic dysphoria: towards a new synthesis.

RATIONALE: Neuroleptic dysphoria (ND) is a subtle and under-recognized side effect of antipsychotic drugs. It is an all-inclusive descriptive phrase that encompasses a variety of unpleasant subjective changes in arousal, mood, thinking and motivation induced by neuroleptic drugs. Understanding this phenomenon has wide ranging clinical and research implications. OBJECTIVE: The present review examined the themes identified in the original studies from the neuroleptic era in the light of recent findings from neuroimaging research, cumulative experience with second generation antipsychotic drugs, and new concepts such as pleasure responsivity, hedonic regulation and subjective tolerability. METHODS: Empirical studies on neuroleptic drugs involving clinical populations treated for schizophrenia, Tourette's disorder and stuttering, studies performed on normal healthy volunteers and selected experimental studies in animals, are reviewed. RESULTS: Dysphoric responses occur early during treatment and typically manifest as a dislike towards medication (drug aversiveness). Dysphoria persisting over time, may lead to adverse clinical consequences such as treatment non-adherence, substance abuse, poor clinical outcome, increased suicidality and compromised quality of life. Interference with the physiological processes of hedonic capacity by the neuroleptics due to their dopaminergic blocking action in the prefrontal cortex and the shell of nucleus accumbens is the putative mediating mechanism underlying the occurrence of dysphoric responses. Second generation antipsychotic drugs with an atypical receptor blocking profile are less likely to elicit dysphoric responses. CONCLUSION: Viewing neuroleptic dysphoria within a broader spectrum of disorders of subjective tolerability and exploring its neurobiological mechanisms is relevant to addressing the nuances of antipsychotic therapy, and could help unravel the questions surrounding the pathophysiology of depression, substance abuse and other dysphoric clinical states.

Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging.

Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D(2)) function with (123)IBZM-SPECT imaging. Results showed a wide variability in the occurrence and severity of dysphoric responses, clearly distinguishing a dysphoric group from non-dysphoric responders. Severity of dysphoric responses, measured by standardized rating scales, correlated inversely with changes in D(2) receptor binding ratios (r = +0.82, p <.01). These results support the notion that striatal dopaminergic activity is not uniformly elevated in all schizophrenic patients, and the sub-group of individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic blocking drugs.

Cannabis induced dopamine release: an in-vivo SPECT study.

In a research study aimed at examining the alterations in dopaminergic function in schizophrenia, the authors identified a surreptitious case scenario which provided new insights into the subjective and neurochemical effects of cannabis. A 38-year-old drug-free schizophrenic patient took part in a single photon emission computerized tomographic (SPECT) study of the brain, and smoked cannabis secretively during a pause in the course of an imaging session. Cannabis had an immediate calming effect, followed by a worsening of psychotic symptoms a few hours later. A comparison of the two sets of images, obtained before and immediately after smoking cannabis, indicated a 20% decrease in the striatal dopamine D2 receptor binding ratio, suggestive of increased synaptic dopaminergic activity. This observation offers a plausible biological explanation for the psychotogenic effects of cannabis in vulnerable individuals, and also raises speculations about an interaction between cannabinoid and dopaminergic systems in the brain reward pathways.

An innovative approach to clinical communication in schizophrenia: the approaches to schizophrenia communication checklists.

Side effects from antipsychotic medications can have a profound effect on patients' lives and may adversely affect their willingness to comply with treatment. Identification of side effects through improved communication between psychiatrists, other members of the healthcare team, and their patients might increase treatment compliance. The Approaches to Schizophrenia Communication (ASC) Steering Group developed two simple, practical checklists for use in the busy clinical setting. The ASC-Self-Report (ASC-SR) checklist is completed by the patient and comprises a list of the more common or clinically important side effects of antipsychotic treatment. The ASC-Clinic (ASC-C) checklist is completed by both clinician and patient together, being used as the basis for a semi-structured interview. In a multicenter pilot study set up to evaluate the utility of checklists, 86% of patients responding considered the ASC-SR to be useful in communicating their problems to psychiatrists and other members of the healthcare team. All healthcare team respondents found both checklists to be helpful when discussing side effect problems with their patients. Moreover, 41% and 47% of healthcare team respondents reported that the ASC-SR and ASC-C, respectively, had assisted them in identifying side-effect problems not previously acknowledged. Preliminary evaluation of the ASC-SR and ASC-C in this multicenter pilot study suggests that both tools were user-friendly, encouraged communication between patients and healthcare professionals about antipsychotic drug side effects, and could readily integrated into everyday clinical practice.

Intervention research in psychosis: issues related to the assessment of quality of life.

Quality of life has emerged as the ideal of modern medicine viewed from a biopsychosocial perspective. The concept has been increasingly used as an important attribute in patient care and clinical studies as well as the basis in many health economic evaluations. Although the concept has been extensively applied in a number of other medical fields such as oncology, cardiovascular, and arthritis, it is only recently that quality of life has received serious attention in the study of severe psychiatric disorders. For the concept to be meaningfully applied in the study of these disorders, several basic and methodological issues have to be adequately resolved. Five such issues are identified: definition of quality of life, the subjective/objective dichotomy, significant determinants of quality of life, how quality of life is measured, and the role of quality of life in clinical management and health economics. Unless these issues are adequately clarified and resolved, the recent heightened interest in the concept of quality of life may fade away, and that would be a missed opportunity in the mental health field.

Assessing health utilities in schizophrenia. A feasibility study.

BACKGROUND: Utility, a concept derived from economics, is the desirability or preference that individuals exhibit for a certain health state. Utility measurement could be viewed as an alternative means of appraising the quality of life of individuals affected by a chronic illness such as schizophrenia. Traditional techniques of utility measurement involve 2 steps: (i) identifying the different health states experienced by individuals during the course of an illness; and (ii) assigning them numerical values known as utilities. AIM: The study examined the feasibility issues and psychometric aspects of obtaining accurate health state descriptions and their utilities from symptomatically stable patients with schizophrenia. METHODS: The study used a cross-sectional, case-controlled design, with a study group consisting of 120 clinically stabilised patients with schizophrenia and a control group of 32 treated and recovered patients with major depression. Patients were asked to provide detailed descriptions of 3 distinct health states associated with their illness: current state, worst state experienced since the onset of illness and a perfect state desired in the future. Further, patients were asked to assign utilities to these health states with the aid of a purpose-built evaluation protocol comprising Magnitude Estimation (ME), Rating Scale (RS), Standard Gamble (SG), Time Trade-Off (TTO) and Willingness-to-Pay (WTP) techniques. The battery was repeated after a 1-week interval. Independent raters assessed symptom severity, insight and quality of life, and nurse-clinicians involved in their care were asked to provide the utility ratings of their clients' mental health state. Patients' opinions about the acceptability of utility measurement techniques, and the respondent burden were also ascertained. RESULTS: Compared with control patients with treated depression, patients with schizophrenia were able to distinguish and describe the specified health states with an equal degree of ease and accuracy. RS, TTO and WTP techniques emerged as the favoured methods of utility evaluation. The test-retest reliability of utility ratings (r = 0.87 to 0.97; p < 0.001) was high, and concurrent validity with the quality of life measures was acceptable. Reliability and validity of patients' appraisals were unaffected by symptoms severity and insight. The accuracy of nurse-clinicians' appraisals were dependent on their close familiarity with the patients and their illness. CONCLUSION: Clinically stabilised patients with schizophrenia can provide accurate health state descriptions and assign them utilities with a fair degree of reliability and validity. Utility evaluations based on patients' self-appraisals can be seen as potential tools in outcome studies and clinical trials involving patients with schizophrenia, but the methodology requires further refinement to accommodate the limitations imposed by the patients' disturbed mental status.

The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

Cost-utility analysis in schizophrenia.

Estimation of quality of life is important to the study of the pharmacoeconomics of schizophrenia. The subject has gained popularity among policymakers, clinicians, and patients and their families, since the advent of new antipsychotic medications that are more expensive than older drugs yet have been shown to cause fewer side effects. Quantifying quality of life has been difficult, since studies often inconsistently define the concept or use rating scales that are inappropriate for the patient population. Utility analysis is a procedure that calculates subjects' preferences regarding living with various health states, given such options as trading more years of life at a lowered health state for dying sooner but having a strong health state during the last years of life. The feasibility of performing utility analysis among patients with schizophrenia was recently examined in a study carried out by the authors. This article reflects initial observations from that study of utility analysis and includes a discussion of problems still facing the study of quality of life and utility analysis.

Quality of life and new antipsychotics in schizophrenia. Are patients better off?

The recent introduction of several antipsychotic medications has raised expectations for better pharmacological management of schizophrenia. Although conventional and new neuroleptics (Risperidone, Olanzapine, Seroquel and soon to be released Ziprasidone) are generally comparable in terms of efficacy; the new antipsychotic medications possess a better side-effects profile and are overall, much better tolerated. The reintroduction of Clozapine as an effective antipsychotic for treatment refractoriness has also improved management for a segment of the schizophrenic population who failed to respond adequately to other antipsychotic medications. Such increased benefits from new antipsychotic medications come with a higher acquisition cost that has somewhat strained the historically low psychiatric budgets. The question then was whether the expected benefits of the new antipsychotics can offset the high cost of these medications in the long-term. In that context, quality of life assessment has provided a tool for the comparative analysis of new and conventional antipsychotic medications, particularly regarding their impact on functional status and satisfaction. In a recently concluded study, we demonstrated that the new antipsychotic medications are subjectively much better tolerated and have a more favourable impact on quality of life compared with conventional neuroleptics. The ultimate question is whether such favourable benefits can translate in the future into better compliance with medications and improved long-term outcomes.

Patient satisfaction and acceptability of long-term treatment with quetiapine.

Satisfaction with, and subjective tolerability of, antipsychotic medication have emerged as important factors in determining treatment compliance and eventual outcome in the management of psychotic disorders. The acceptability of long-term treatment with quetiapine, an atypical antipsychotic agent with a lower incidence of extrapyramidal effects than standard therapy, was examined in this open-label, multicentre study of patient satisfaction. One hundred and twenty-nine patients with major psychiatric disorders, who had each been receiving quetiapine for at least 6 months in open-label extension studies, were asked to complete a 7-item questionnaire concerning subjective experience and satisfaction with treatment. Over 75% of respondents indicated that they were either "very" or "extremely" satisfied with their antipsychotic medication while 73.7% indicated that, over the last month, they regarded their antipsychotic medication to have been "very" or "extremely" helpful. Subjectively reported side-effects were uncommon, with 74.4% of patients reporting no side-effects, 23.3% mild side-effects and only 2.3% moderate side-effects. There were no unambiguous reports of extrapyramidal symptoms. An overwhelming majority of patients (114/118; 96.6%) reported that they preferred quetiapine to previous antipsychotic medications, the predominant reasons being their perceptions of better tolerability and greater efficacy. Patients also identified improvements in quality of life and their activities of daily living. These positive evaluations appeared to be reflected in the high proportion of respondents who indicated a readiness to continue quetiapine treatment. This study indicates that the combination of efficacy and a favourable tolerability profile shown by quetiapine may result in benefits that are evident to the patient and may be reflected in high levels of patient satisfaction and acceptance of treatment. By improving compliance with treatment, these benefits may also enhance clinical outcome.

Quality of life measurement in schizophrenia: reconciling the quest for subjectivity with the question of reliability.

BACKGROUND: The patients' ability to appraise their quality of life in schizophrenia was studied by examining the reliability and the validity of self-rated quality of life estimates. METHODS: Sixty-three symptomatically stable patients with schizophrenia (DSM-IV) receiving maintenance treatment were evaluated over a 4-week period. The subjects were asked to appraise their quality of life at weekly intervals on a single item global quality of life measure, as well as the self-administered sickness impact profile. The patients' quality of life was also rated by a clinician using the social performance schedule and the global assessment scale of functioning; and clinical aspects such as the severity of psychotic symptoms, neurocognitive deficits, dose of medications, and side effects were documented with standardized measures. RESULTS: The results indicated that the patients' self-reports were highly consistent over the 4 weeks, and the quality of life ratings correlated significantly with the clinician's estimates. The patients' quality of life was predictably influenced by the severity of their symptoms, side effects, cognitive deficits and the dose of their antipsychotic medication, but the reliability of their reports was not materially affected by these factors. CONCLUSIONS: It is concluded that clinically compliant and stable patients with schizophrenia can evaluate and report their quality of life with a high degree of reliability and concurrent validity, implying that self-report measures are potentially useful tools in clinical trials and outcome studies.

The influence of neurocognitive deficits and symptoms on quality of life in schizophrenia.

The purpose of the present study was to examine the relationship between neurocognitive deficits and self-reported quality of life in order to examine whether neurocognitive impairment interferes with any aspects of quality of life for patients with schizophrenia. Forty-two outpatients with stable chronic schizophrenia were assessed for neurocognitive deficits using a computerized test battery, and all patients completed a version of the Sickness Impact Profile (SIP) to assess their quality of life across a variety of domains. The neurocognitive assessment tests revealed significant deficits compared with normal control subjects, particularly with respect to impaired iconic memory and frontal functioning. Patients reported that their quality of life was compromised. Despite the substantiation of marked neurocognitive deficits and reduced quality of life, correlations between neurocognitive deficits and quality of life were largely nonsignificant or very weak. Symptom expression, however, particularly with regard to general psychopathology on the Positive and Negative Syndrome Scale (PANSS), was significantly associated with quality of life. These results suggest that neurocognitive deficits in schizophrenia, while often profound, appear to have little direct impact on the patient's perceived quality of life.

Quality of life and response of negative symptoms in schizophrenia to haloperidol and the atypical antipsychotic remoxipride. The Canadian Remoxipride Group.

In a large, multicenter, double-blind study of the effect of haloperidol and the atypical antipsychotic remoxipride on improvement of negative symptoms in schizophrenia, quality of life was also assessed using a modified version of the Sickness Impact Profile (SIP). Compared with previous studies, this study had a longer duration (28 weeks), and the dose of the comparator, haloperidol, was much lower. At the end of the study, compared with the baseline, both treatment groups reported comparable improvement in negative symptoms as defined by the protocol (at least 20% improvement). Similarly, both groups showed comparable changes on global and multidimensional self-assessments of quality of life. All the subfactors of the modified version of the SIP were similar in both groups, except for the subfactor that relates to alertness behavior, which possibly reflects remoxipride's lack of any sedating properties compared with haloperidol. This study presents an approach for inclusion of quality of life as an outcome measure in the design of clinical trials of new antipsychotic medications.