Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand

Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone. (C) 2002 Elsevier Science B.V. All rights reserved.

Palliative care at home: general practitioners working with palliative care teams

Home care is the preferred option for most people with a terminal illness. Providing home care relies on good community-based services, and a general practice workforce competent in palliative care practice and willing to accommodate patients' needs. Structured palliative care training of general practitioners is needed at undergraduate and postgraduate level, with attention to barriers to teamwork and communication. Good palliative care-can be delivered to patients at home by GPs (supported by specialist palliative care teams) and community nurses, with access to an inpatient facility when required. To optimise patient care, careful planning and good communication between all members of the healthcare team is crucial.

Attenuation of perceptual asymmetries in patients with early-onset schizophrenia: Evidence in favour of reduced hemispheric differentiation in schizophrenia?

Lateral biases in visual perception have been demonstrated in normal individuals and in patients with unilateral brain lesions. It has been suggested that the absence of structural and functional asymmetries in schizophrenia could be due to a failure in lateralisation that may be most pronounced in those patients whose illness onset is at an early age. Here we examined lateral biases in patients with schizophrenia of an early onset (N = 21) and a late onset.(N = 19), and their respective age-matched control groups, using the greyscales task, a sensitive measure of asymmetries in visual processing. The stimuli consisted of two rectangles, one above the other, shaded in opposite directions and matched overall for darkness. Participants judged which of the two rectangles looked darker overall. Previous studies using this task in healthy participants have reported a reliable bias, such that the rectangle with the darker end on the left is selected preferentially. Whereas the late-onset patients in this study exhibited a perceptual bias of similar direction and magnitude to that of controls, this was not the case for the early-onset patients, who exhibited significantly less bias than their control group. The reduced perceptual bias seen in the early-onset group, but not the late-onset group, suggests an attenuation of right hemisphere mechanisms dedicated to processing vistiospatial information. The attenuated perceptual asymmetry in the early-onset group only may be consistent with the view that (i) an earlier illness onset reflects a greater loss of hemispheric differentiation and (ii) reduced functional asymmetries in the early-onset group are a manifestation of a failure to allocate functions to one or the other hemisphere.

The role of impulsivity in the development of substance use and eating disorders

Impulsivity is now widely viewed as a multidimensional construct consisting of a number of related dimensions. Although many measures of impulsivity are correlated, most recent factor analyses support at least a two-factor model. In the current paper, these two factors have been labelled reward sensitivity, reflecting one of the primary dimensions of Gray's personality theory, and rash-spontaneous impulsiveness. The evidence supporting the existence of two dimensions of impulsivity is reviewed in relation to substance misuse and binge eating. (C) 2004 Elsevier Ltd. All rights reserved.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood and adult-onset schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages. (C) 2004 Published by Elsevier Inc.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders

Background: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Health Funding Authority. This paper presents CPGs for schizophrenia and related disorders. Over the past decade schizophrenia has become more treatable than ever before. A new generation of drug therapies, a renaissance of psychological and psychosocial interventions and a first generation of reform within the specialist mental health system have combined to create an evidence-based climate of realistic optimism. Progressive neuroscientific advances hold out the strong possibility of more definitive biological treatments in the near future. However, this improved potential for better outcomes and quality of life for people with schizophrenia has not been translated into reality in Australia. The efficacy-effectiveness gap is wider for schizophrenia than any other serious medical disorder. Therapeutic nihilism, under-resourcing of services and a stalling of the service reform process, poor morale within specialist mental health services, a lack of broad-based recovery and life support programs, and a climate of tenacious stigma and consequent lack of concern for people with schizophrenia are the contributory causes for this failure to effectively treat. These guidelines therefore tackle only one element in the endeavour to reduce the impact of schizophrenia. They distil the current evidence-base and make recommendations based on the best available knowledge. Method: A comprehensive literature review (1990-2003) was conducted, including all Cochrane schizophrenia reviews and all relevant meta-analyses, and a number of recent international clinical practice guidelines were consulted. A series of drafts were refined by the expert committee and enhanced through a bi-national consultation process. Treatment recommendations: This guideline provides evidence-based recommendations for the management of schizophrenia by treatment type and by phase of illness. The essential features of the guidelines are: (i) Early detection and comprehensive treatment of first episode cases is a priority since the psychosocial and possibly the biological impact of illness can be minimized and outcome improved. An optimistic attitude on the part of health professionals is an essential ingredient from the outset and across all phases of illness. (ii) Comprehensive and sustained intervention should be assured during the initial 3-5 years following diagnosis since course of illness is strongly influenced by what occurs in this 'critical period'. Patients should not have to 'prove chronicity' before they gain consistent access and tenure to specialist mental health services. (iii) Antipsychotic medication is the cornerstone of treatment. These medicines have improved in quality and tolerability, yet should be used cautiously and in a more targeted manner than in the past. The treatment of choice for most patients is now the novel antipsychotic medications because of their superior tolerability and, in particular, the reduced risk of tardive dyskinesia. This is particularly so for the first episode patient where, due to superior tolerability, novel agents are the first, second and third line choice. These novel agents are nevertheless associated with potentially serious medium to long-term side-effects of their own for which patients must be carefully monitored. Conventional antipsychotic medications in low dosage may still have a role in a small proportion of patients, where there has been full remission and good tolerability; however, the indications are shrinking progressively. These principles are now accepted in most developed countries. (vi) Clozapine should be used early in the course, as soon as treatment resistance to at least two antipsychotics has been demonstrated. This usually means incomplete remission of positive symptomatology, but clozapine may also be considered where there are pervasive negative symptoms or significant or persistent suicidal risk is present. (v) Comprehensive psychosocial interventions should be routinely available to all patients and their families, and provided by appropriately trained mental health professionals with time to devote to the task. This includes family interventions, cognitive-behaviour therapy, vocational rehabilitation and other forms of therapy, especially for comorbid conditions, such as substance abuse, depression and anxiety. (vi) The social and cultural environment of people with schizophrenia is an essential arena for intervention. Adequate shelter, financial security, access to meaningful social roles and availability of social support are essential components of recovery and quality of life. (vii) Interventions should be carefully tailored to phase and stage of illness, and to gender and cultural background. (viii) Genuine involvement of consumers and relatives in service development and provision should be standard. (ix) Maintenance of good physical health and prevention and early treatment of serious medical illness has been seriously neglected in the management of schizophrenia, and results in premature death and widespread morbidity. Quality of medical care for people with schizophrenia should be equivalent to the general community standard. (x) General practitioners (GPs)s should always be closely involved in the care of people with schizophrenia. However, this should be truly shared care, and sole care by a GP with minimal or no special Optimal treatment of schizophrenia requires a multidisciplinary team approach with a consultant psychiatrist centrally involved.

What is an effective health consumer? A convergent interviewing approach

This study is part of a larger project on the measurement of effective health consumers in the context of musculoskeletal illness. This complex issue involves the progressive nature of the disease, invisibility of the illness and attendant impairments, complexity of decision-making and negotiation, and urgent need to translate emergent evidence about treatment and management to patients and health professionals. We conducted indepth interviews with patients, family members, general practitioners, specialist clinicians, and health consumer advocates (N = 84) about effective consumers in this context, using a process of convergent interviewing, with convergence conducted within and across groups and countries. The initial set of themes included information seeking and adaptation, decision-making, roles of patients, GPs, and specialists and communication between them, importance of pain and impact of depression, impact of the social environment (including the invisibility of the disease and the need for a normal life), and coping strategies.

Constipation in intensive care unit: Incidence and risk factors

Purpose: Although gastrointestinal motility disorders are common in critically ill patients, constipation and its implications have received very little attention. We aimed to determine the incidence of constipation to find risk factors and its implications in critically ill patients Materials and Methods: During a 6-month period, we enrolled all patients admitted to an intensive care unit from an universitary hospital who stayed 3 or more days. Patients submitted to bowel surgery were excluded. Results: Constipation occurred in 69.9% of the patients. There was no difference between constipated and not constipated in terms of sex, age, Acute Physiology and Chronic Health Evaluation II, type of admission (surgical, clinical, or trauma), opiate use, antibiotic therapy, and mechanical ventilation. Early (<24 hours) enteral nutrition was associated with less constipation, a finding that persisted at multivariable analysis (P < .01). Constipation was not associated with greater intensive care unit or mortality, length of stay, or days free from mechanical ventilation. Conclusions: Constipation is very common among critically ill patients. Early enteral nutrition is associated with earlier return of bowel function. (C) 2009 Elsevier Inc. All rights reserved.

Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes. However, there is lack of information on how and under what conditions continuous renal replacement therapy is discontinued. Design: Post hoc analysis of a prospective observational study. Setting. Fifty-four intensive care units in 23 countries. Patients: Five hundred twenty-nine patients (52.6%) who survived initial therapy among 1006 patients treated with continuous renal replacement therapy. Interventions: None. Measurements and Main Results., Three hundred thirteen patients were removed successfully from continuous renal replacement therapy and did not require any renal replacement therapy for at least 7 days and were classified as the ""success"" group and the rest (216 patients) were classified as the ""repeat-RRT"" (renal replacement therapy) group. Patients in the ""success"" group had lower hospital mortality (28.5% vs. 42.7%, p < .0001) compared with patients in the ""repeat-RRT"" group. They also had lower creatinine and urea concentrations and a higher urine output at the time of stopping continuous renal replacement therapy. Multivariate logistic regression analysis for successful discontinuation of continuous renal replacement therapy identified urine output (during the 24 hrs before stopping continuous renal replacement therapy: odds ratio, 1.078 per 100 mL/day increase) and creatinine (odds ratio, 0.996 per mu mol/L increase) as significant predictors of successful cessation. The area under the receiver operating characteristic curve to predict successful discontinuation of continuous renal replacement therapy was 0.808 for urine output and 0.635 for creatinine. The predictive ability of urine output was negatively affected by the use of diuretics (area under the receiver operating characteristic curve, 0.671 with diuretics and 0.845 without diuretics). Conclusions. We report on the current practice of discontinuing continuous renal replacement therapy in a multinational setting. Urine output at the time of initial cessation (if continuous renal replacement therapy was the most important predictor of successful discontinuation, especially if occurring without the administration of diuretics. (Crit Care Med 2009; 37:2576-2582)

Juvenile dermatomyositis and toxoplasmosis: a rare association

Dermatomyositis is an unknown cause`s disease that in general is characterized by muscular inflammation with weakness and typical skin rash (heliotrope and Gottron`s papules). In this article we describe a 13-year-old girl with juvenile dermatomyositis associated with toxoplasmosis. Myositis was treated with corticosteroids and immunosuppressive drugs, but she had good response only after anti-parasitary drug was started.-

Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Results: Timing of RRT was stratified into ""early"" and ""late"" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea <= 24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 mu mol/L vs 71.4% for creatinine <= 309 mu mol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001).However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence. Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. (C) 2009 Elsevier Inc. All rights reserved.

Pathogenesis of napkin dermatitis - Part I

Irritant contact dermatitis is the most prevalent diaper dermatitis and, probably, the most common cause of skin disease in infancy. The wearing of diaper leads to overhydration, increased local temperature and humidity. Constant maceration and prolonged contact with urine and stools makes the skin under the diaper more susceptible. There is often secondary infection due to Candida or bacteria, such as Bacillus faecallis, Proteus, Pseudomonas, Staphylococcus e Streptococcus. Oils, soaps, powders and ointments can be irritants and aggravate the rash. It is important to know the pathophysiology of the disease for appropriate treatment and prevention.

Long-Term Prospective, Randomized, Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients The REMADHE Trial

Background-The effectiveness of heart failure disease management proarams in patients under cardiologists` care over long-term follow-up is not established. Methods and Results-We investigated the effects of a disease management program with repetitive education and telephone monitoring on primary (combined death or unplanned first hospitalization and quality-of-life changes) and secondary end points (hospitalization, death, and adherence). The REMADHE [Repetitive Education and Monitoring for ADherence for Heart Failure] trial is a long-term randomized, prospective, parallel trial designed to compare intervention with control. One hundred seventeen patients were randomized to usual care, and 233 to additional intervention. The mean follow-up was 2.47 +/- 1.75 years, with 54% adherence to the program. In the intervention group, the primary end point composite of death or unplanned hospitalization was reduced (hazard ratio, 0.64; confidence interval, 0.43 to 0.88; P=0.008), driven by reduction in hospitalization. The quality-of-life questionnaire score improved only in the intervention group (P<0.003). Mortality was similar in both groups. Number of hospitalizations (1.3 +/- 1.7 versus 0.8 +/- 1.3, P<0.0001), total hospital days during the follow-up (19.9 +/- 51 versus 11.1 +/- 24 days, P<0.0001), and the need for emergency visits (4.5 +/- 10.6 versus 1.6 +/- 2.4, P<0.0001) were lower in the intervention group. Beneficial effects were homogeneous for sex, race, diabetes and no diabetes, age, functional class, and etiology. Conclusions-For a longer follow-up period than in previous studies, this heart failure disease management program model of patients under the supervision of a cardiologist is associated with a reduction in unplanned hospitalization, a reduction of total hospital days, and a reduced need for emergency care, as well as improved quality of life, despite modest program adherence over time. (Circ Heart Fail. 2008;1:115-124.)

Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age ! 15 years, and continuous HAART for >= 6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load 15000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = 033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.