Neuropsychiatric adverse effects of interferon-alpha: recognition and management

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.     

Immunomodulatory effects of the fungicide Mancozeb in agricultural workers

Available data suggest that ethylenebisdithiocarbamates (EBDCs) may have immunomodulatory effects. This study aimed to investigate the immunological profile of farmers exposed to Mancozeb, an EBDC fungicide, through the determination of several serum, cellular, and functional immune parameters. Twenty-six healthy subjects entered the study, 13 vineyards exposed to Mancozeb and 13 unexposed controls. Exposure was assessed through the determination of ethylentiourea (ETU) in urine. Complete and differential blood count, serum immunoglobulins, complement fractions, autoantibodies, lymphocyte subpopulations, proliferative response to mitogens, natural killer (NK) activity, and cytokine production were measured. Post-exposure samples showed ETU urine concentration significantly higher than pre-exposure and control groups. A significant increase in CD19+ cells, both percentage and absolute number, and a significant decrease in the percentage of CD25+ cells were found in post-exposure samples compared to controls. A statistically significant increase in the proliferative response to phorbol myristate acetate plus ionomycin (PMA + ionomycin) was observed in the post-exposure group compared to controls and baseline, while a significant reduction in LPS-induced TNF-alpha release in post-exposure samples was observed. Overall, our results suggest that low-level exposure to Mancozeb has slight immunomodulatory effects, and point out a method adequate to reveal immune-modifications in workers occupationally exposed to potential immunotoxic compounds, based on a whole blood assay.     

Nurse practitioner-led home care curriculum for third-year medical students

Recent data have shown that medical students do not receive adequate exposure to the practice of home care. The number of homebound people is expected to increase, and health care services for these patients will need to expand. A one-week didactic and clinical curriculum was designed and implemented by four nurse practitioners in the Visiting Doctors Program, to provide home care exposure to medical students. The program stresses the medical, psychosocial and palliative aspects of patient care. The students evaluated both the nurse practitioners and the program favorably, using a five-point Likert scale. Role modeling and professionalism were noted to be of value to the students, and bear further study in the context of medical school curricula for home care.     

Anti-inflammatory and antimicrobial effect of lectin from Lonchocarpus sericeus seeds in an experimental rat model of infectious peritonitis

We have investigated the anti-inflammatory and antimicrobial effect of the lectin from Lonchocarpus sericeus seeds (LSL) in a model of infectious peritonitis in adult Wistar rats. Animals were treated with saline or LSL (10 mg kg(-1), i.v) immediately and 6 h after the induction of peritonitis via cecal ligation and single puncture. Twelve hours after surgery, animals were killed and the infectious process was monitored by total and differential count of cells from blood and peritoneal washing liquid, adenosine deaminase activity, antibiogram and the number of viable bacteria of the peritoneal cavity. LSL treatment decreased the inflammatory response evoked by the induction of peritonitis, as seen by the inhibition of neutrophil migration into peritoneal cavities, leucocytosis and reduction of adenosine deaminase activity in the peritoneal fluid. All these effects were reversed by the lectin association to N-acetyl-glucosamine. LSL in-vitro did not show any antimicrobial action, but promoted a marked decrease of the viable bacterial population in peritoneal cavities. In conclusion, LSL inhibited the inflammatory response and the bacterial colonization of infectious peritonitis in rats.     

Access to medical appointments by men with sexually transmitted diseases at a health unit in Fortaleza, Ceará, Brazil

Access to healthcare services is one of the important aspects of the Unified National Health System in Brazil, and the supply and management of such services is the responsibility of municipalities. This study focuses on difficulties faced by men with sexually transmitted diseases (STDs) in accessing appointments for treatment. This was a qualitative study of men treated at an STD clinic in Fortaleza, Ceará State, Brazil, in November 2003, using content analysis technique and interpretation of interviews, focusing on access as the category. Men with STDs encountered extensive difficulty in accessing medical appointments, even when they used different strategies for this purpose. Scheduling of services is incompatible with patients' available time. At the primary care level, the supply of appointments for STDs scarcely exists. More investment is needed in the Unified National Health System in order to improve access to appointments for men with STDs, and the supply of services should take the population's demand into account.     

Difficulties experienced by the patient care team at the intensive care unit

This interpretative case study aimed to identify the difficulties experienced by the patient care team while working at the Intensive Care Unit. Data were collected through participant observation and semistructured interviews with doctors, nurses and nurse's aides. Two major categories emerged from the data analysis: Care delivery in intensive care-- "it is difficult to deal with death and inform the patient's family" and care delivery in intensive care-- "the lack of material resources and the difficulty to work in a team". The difficulties are related to the contact with family members, dealing with death and the lack of material resources, and particularly with the relation between team members. Therefore, teams need to promote opportunities and discussions to reflect on the technical, scientific and ethic aspects of care for critical patients as well as family members, with a view to better care quality and interpersonal relations.     

Hospital admissions forms versus medical records to assess risk of in-hospital death from acute myocardial infarction in Rio de Janeiro, Brazil

The objective of this study was to analyze the usefulness of the Brazilian Hospital Information System (SIH) in comparison to medical records to study factors associated with in-hospital mortality due to acute myocardial infarction (AMI). We evaluated a stratified random sample of 391 medical records (out of 1,936 hospital admissions forms) with AMI as the primary diagnosis in the city of Rio de Janeiro. Factors associated with in-hospital death were studied through logistic modeling. Models were developed directly from the SIH and from medical records. ROC curves were constructed to allow comparison of the different models. We found an AMI diagnostic confirmation = 91.7% and hospital mortality = 20.6%. The logistic model derived from medical records produced the best fit (concordance = 90.1%). Although the SIH model had a worse fit (concordance = 70.6%), the correction of keying-in and information errors using data from medical records did not significantly modify its performance. Under-recording of secondary diagnosis was high in the SIH forms and was the main limiting factor.     

Breast feeding in a population attended by the family health program--FHP

This study aimed to identify the prevalence of different types of breastfeeding and how they relate to maternal variables in the municipality of Conchas, S?o Paulo, Brazil, which is fully covered by the family health program. We collected information about the current eating habits of children under one year old who were attended during the 2003 Multivaccination Campaign. Associations were submitted to the chi-square test, adopting p<0.05 as the critical level. The prevalence rates for exclusive breastfeeding (EB) and predominant breastfeeding (PB) in 4-month-olds and younger were 25.4% and 44.4%, respectively, and 66.7% of the children under one were still being breastfed. Prevalence for EB in 6-month-olds and younger was heterogeneous, ranging from 7.4 to 41.2% according to the children's region of origin in the FHP. Difficulties at the beginning of breastfeeding were associated with lower prevalence rates for EB and PB. These results show a situation far from WHO recommendations and from that situation in which there is evidence that children's health receives maximum protection, reiterate the need to support mothers in the early puerperal period and demonstrate the importance of diagnoses separated per regions for actions aimed at promoting breastfeeding.