Attitudes of general hospital consultants towards psychosocial and psychiatric problems in Netherlands.

Psychosocial and psychiatric problems are common in patients admitted to general hospitals, and can negatively influence course of somatic diseases. Hence, early identification and adequate management is important. The aim of this study is to investigate attitudes towards psychosocial and psychiatric problems by non-psychiatrist consultants in an academic hospital. Data were collected by anonymous, self- administered questionnaires which were provided to all consultants during morning reports and by email. Of 431 eligible participants, 187(43%) completed the questionnaire: 64% during morning reports, and 36% by email. Almost all consultants report generally positive attitudes towards mental health problems. However, we identified several obstacles towards management. First, there was a discrepancy between positive attitude and the willingness to take on management responsibility. Reported reasons for this discrepancy were time constraints and lack of skills. We also found that consultants feel little responsibility for the management of depression and chronic drinking. Physicians have generally more positive attitudes than surgeons. Finally, all consultants are less likely to refer patients with dementia and treatment non-compliance to psychiatry, for reasons of perceived ineffectiveness and fear of stigmatizing patients. We conclude targeted education on the management of these problems for hospital consultants is still warranted.

Evidence-based medicine in practice.

Evidence-based medicine (EBM) has emerged as a dominant paradigm in healthcare, strongly influencing clinical decision-making, access to and funding for interventions. However, EBM has a number of limitations, which appear to have been under-represented in the literature. We explore the development and shortcomings of EBM, and consider a complementary role for practice-based evidence in guiding clinical decision-making. EBM is a valuable and important part of the medical landscape. However, a range of significant limitations makes over-reliance on this paradigm problematic. Appropriate recognition of practice-based evidence helps to bridge the gap between evidence and clinical practices.

Nurses' reported influence on the prescription and use of medication.

AIM: To identify the activities senior nurses report undertaking that may influence the prescription and use of medicines. BACKGROUND: While much attention has focused on the role of nurse prescribing, little is known about the extent to which non-prescribing nurses influence medication decision making. The pharmaceutical industry recognizes this influence in its marketing strategies, and courts nurses by provision of promotional material and sponsorship of nursing professional development. METHODS: We undertook parallel web- and paper-based surveys of 100 senior registered nurses employed by government-funded health boards in two distinct New Zealand regions. FINDINGS: Only 2/96 (2%) of nurses had prescribing rights, yet 74/94 (79%) reported recommending treatments to the prescribing doctor, 74/95 (79%) stated they provided advice to patients about over-the-counter medications and 71/92 (77%) participated in the development of guidelines or policies that include the use of medications. All nurses in this sample reported influencing the prescription of medicines in one way or another. DISCUSSION: From actually writing prescriptions to providing feedback on treatment outcomes, there are many opportunities for nurses to influence the decision making of medical and other prescribers, which open nurses to exploitation from commercial forces. Policy and education regarding prescriber relationships with the pharmaceutical industry should also recognize the role of non-prescribing nurses.

Rationale for a trial of immunosuppressive therapy in acute schizophrenia.

Schizophrenia is a debilitating, costly, socially disruptive, life-threatening disease in which available treatments are largely palliative and empirical, and produce significant short- and long-term side effects. Therefore, a strong case can made for exploring alternative treatments with a rational basis for use in this disease. Considerable evidence indicates that autoimmune processes may be involved in some forms of schizophrenia, including altered risk of certain autoimmune diseases in patients and their relatives, shared epidemiological features, and apparent involvement of genes known to influence the immune response repertoire. Attempts to provide direct evidence for autoimmune processes have proven elusive, possibly due to the technical difficulty inherent in accessing autoantibodies with high affinity for brain cell-surface receptors. In view of this impasse, we argue for a well-designed trial in schizophrenia of immunosuppressive therapy, which is now the mainstay of therapy for many autoimmune diseases. Analysis of disease states in which immunosuppression has been effectively used over many decades provides guidelines necessary for a meaningful trial.

Hepatitis C virus acute quadriparetic vasculitic neuropathy responsive to cyclophosphamide.

PURPOSE: Hepatitis C viral [HCV] infection is a chronic multisystem disorder that may have an indolent course initially. Peripheral neuropathy associated with cryoglobulinemia and a systemic vasculitis is a well-described complication of HCV infection. But this neuropathy is not known to have a late-onset acute fulminant phase. This acute fulminant phase is characterized by quadriparesis associated with pulmonary and/or renal insufficiency, and it may occur despite adequate treatment for HCV infection. The purpose of this study is to report that patients treated for chronic HCV infection may manifest a secondary progressive acute fulminant neuropathy associated with respiratory and/or renal insufficiency that is responsive to cyclophosphamide. METHODS: Case series retrospective data analysis. RESULTS: Three patients with biopsy-proven HCV associated vasculitic neuropathy manifested a secondary progressive acute fulminant course resulting in quadriparesis within 5 years of the initial diagnosis. Complete remission was achieved with cyclophosphamide therapy such that all patients became ambulatory. CONCLUSIONS: HCV-associated vasculitic neuropathy may manifest a secondary phase, which is acute, fulminant and progressive that is superimposed on an otherwise slowly progressive disorder. Cyclophosphamide therapy may abort progression and induce remission of this acute fulminant phase.

Short term treatment with St. John's wort, hypericin or hyperforin fails to induce CYP450 isoforms in the Swiss Webster mouse.

This investigation was designed to determine whether St. John's wort (SJW)(435 mg/kg/d), a readily available antidepressant, or its purported active constituents hypericin (1 mg/kg/d) and hyperforin (10 mg/kg/d) were able to induce various hepatic cytochrome P450 (CYP450) isoforms. SJW, hypericin and hyperforin were administered to male Swiss Webster mice for four consecutive days and hepatic microsomes were prepared on day 5. None of the three treatments resulted in a statistical change in total hepatic CYP450 (SJW treated 0.95 +/- 0.09 nmol/mg vs control 1.09 +/- 0.14 nmol/mg). Furthermore, the catalytic activities of CYP1A2. CYP2E1 and CYP3A were unchanged from control following all three treatments as determined by ethoxyresorufin O-deethylation, p-nitrophenol hydroxylation and erythromycin N-demethylation respectively. Additionally, western immunoblotting demonstrated that there was no significant change in the polypeptide levels of any of the three isoforms. These results indicate that four days of treatment with moderate to high doses of SJW, hyperforin or hypericin fails to induce these CYP450 isoforms in the male Swiss Webster mouse.

St. John's wort extract induces CYP3A and CYP2E1 in the Swiss Webster mouse.

This investigation was designed to determine the ability of St. John's wort (SJW), a readily available antidepressant, to induce various hepatic drug metabolizing enzymes. SJW (140 or 280 mg/kg/day) was administered to male Swiss Webster mice for 1, 2, or 3 weeks. Enzymatic activity was analyzed in hepatic microsomes for all of the following drug metabolizing enzymes: CYP3A, CYP1A, CYP2E1, and UDP-glucuronosyltransferase (UDPGT). The catalytic activity of CYP1A was unchanged from control following any dose or duration of SJW, while both CYP3A and CYP2E1 catalytic activities were increased 2-fold by both SJW concentrations but only following 3 weeks of administration. Results from Western immunoblotting studies supported the changes in catalytic activity, as protein levels for CYP2E1 and CYP3A were increased (2.5-fold and 6-fold, respectively) following 3 weeks of SJW administration. Additionally, the catalytic activity of the conjugation enzyme UDPGT was unchanged from control following all SJW treatments. These results indicate that in the mouse moderate doses of SJW cause an increase in the catalytic activity and polypeptide levels of CYP2E1 and CYP3A but only following 21 days of administration, while the catalytic activity of CYP1A and UDPGT activity remain unaffected.

Long-term assessment of psychological well-being in a randomized placebo-controlled trial of cholesterol reduction with pravastatin. The LIPID Study Investigators.

BACKGROUND: There is controversial evidence that a low serum cholesterol level is associated with an increased risk of depression, suicide, and violence. The aim of this study was to identify or exclude any small or infrequent adverse effect of long-term reduction of serum cholesterol with pravastatin sodium on psychological well-being. METHODS: The study population consisted of 1130 respondents from a representative sample of 1222 patients with stable coronary artery disease participating in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Subjects were randomized in a double-blind manner to treatment with pravastatin sodium, 40 mg/d (n = 559), or placebo (n = 571) for at least 4 years. Psychological well-being was assessed with a standard self-administered questionnaire at baseline and after 6 months, 1 year, 2 years, and 4 years. The questionnaire assessed anxiety and depression, anger, impulsiveness, alcohol consumption, and adverse life events. RESULTS: Serum cholesterol levels decreased by an average of 1.3 mmol/L (50 mg/dL) with pravastatin therapy and did not change with placebo. During follow-up there was no significant difference by treatment group in measures of anxiety and depression, anger expression, or impulsiveness (95% confidence interval excluded differences of >0.2 SD) and no difference in the proportion of subjects with excessive alcohol consumption or adverse life events (odds ratio, 1.0; 95% confidence interval, 0.8-1.2). There was no evidence of a treatment effect for persons whose baseline serum cholesterol level was in the lowest 10% (<4.6 mmol/L [178 mg/dL]) or whose scores for anxiety and depression, anger, or impulsiveness were in the highest 10% at baseline. There was no association between change in the serum cholesterol level and measures of anxiety and depression, anger, or impulsiveness during follow-up. CONCLUSION: Long-term reduction of serum cholesterol with pravastatin has no adverse effect on psychological well-being.

Current perception threshold: an adjunctive test for detection of acquired demyelinating polyneuropathies.

Current Perception Threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of three sensory fiber subtypes: A-beta (2,000 Hz), A-delta (250 Hz) and C fibers (5 Hz). Demyelinating polyneuropathies tend to affect larger myelinated fibers before smaller unmyelinated fibers, and they usually begin at the proximal nerve roots or terminal axons, due to relative weakness of the blood-nerve barrier in these locations. Axonal polyneuropathies tend to affect smaller fibers before larger fibers, in a distal to proximal gradient. Ten patients with demyelinating polyneuropathy and ten patients with axonal polyneuropathy underwent CPT testing. CPT comparisons were made with regard to side-to-side asymmetries, fiber type involvement, and the ratio of fiber types involved. The C2, lateral antebrachial cutaneous, and sural distributions were examined bilaterally. Demyelinating polyneuropathies were detected with 50% sensitivity and 100% specificity. This diagnostic sensitivity is similar to that of published criteria based upon motor nerve conduction. CPT testing can distinguish demyelinating from axonal polyneuropathies. It may be particularly helpful in patients with predominantly sensory symptoms in whom EMG/NCS data may be equivocal, or in patients who decline EMG/NCS studies.

Interferons, serotonin and neurotoxicity.

BACKGROUND: Interferons are a class of cytokines profoundly affecting immune function. Several interferons are now synthesized and used clinically, notably for viral diseases and cancer. In addition to their desired immune effects, interferons cause a number of toxicities, including prominent effects on the nervous system. METHODS: This literature review focused on the incidence of depression associated with interferon treatment. Possible neurochemical mechanisms and remedial strategies were also considered. RESULTS: Interferon treatment, particularly with the alpha subtype, is unquestionably linked with depression, but the strength of association is uncertain because of erratic ascertainment and pretreatment co-morbidity. A likely pathogenic mechanism has been described, involving interferon suppression of serotonin synthesis. Controlled treatment trials of interferon-induced depression are not yet available. CONCLUSIONS: Neurotoxicity substantially limits the use of interferons. At least some of the risk of depression appears to derive from their anti-serotonergic effects, consistent with the large body of evidence pointing to a general link between serotonin and affective illness. Vigilant detection and aggressive treatment of depression is necessary to optimize interferon treatment of many patients.

Subtyping depression by clinical features: the Australasian database.

OBJECTIVE: To distinguish psychotic, melancholic and a residual non-melancholic class on the basis of clinical features alone. Previous studies at our Mood Disorders Unit (MDU) favour a hierarchical model, with the classes able to be distinguished by two specific clinical features, but any such intramural study risks rater bias and requires external replication. METHOD: This replication study involved 27 Australasian psychiatrist raters, thus extending the sample and raters beyond the MDU facility. They collected clinical feature data using a standardized assessment with precoded rating options. A psychotic depression (PD) class was derived by respecting DSM-IV decision rules while a cluster analysis distinguished melancholic (MEL) and non-melancholic classes. RESULTS: The MELs were distinguished virtually entirely by the presence of significant psychomotor disturbance (PMD), as rated by the observationally based CORE measure, with over-representation on only three of an extensive set of 'endogeneity symptoms'. CONCLUSION: In comparison to PMD, endogeneity symptoms appear to be poor indicators of 'melancholic' type, confounding typology with severity. Results again support the hierarchical model.

Slow-frequency repetitive transcranial magnetic stimulation in a patient with focal cortical dysplasia.

PURPOSE: To evaluate the effect of slow-frequency repetitive transcranial magnetic stimulation (SF-rTMS) on interictal epileptiform activity and seizure frequency in a patient with medically refractory partial seizures due to focal cortical dysplasia. METHODS: A 9-cm circular coil was positioned over the area of cortical dysplasia. One hundred stimuli given at 0.5 Hz at 5% below motor threshold were given biweekly for four consecutive weeks. The EEG was recorded for 30 min before and after the first 100 stimuli. The number of seizures during the month of stimulation was compared with that of the month before stimulation. RESULTS: Stimulation was associated with a 70% reduction in the frequency of seizures and a 77% reduction in the frequency of interictal spikes. No seizures occurred during stimulation. CONCLUSIONS: SF-rTMS was safe and well tolerated in this patient. The reduction in seizures and interictal spikes associated with SF-rTMS supports the concept of SF-rTMS-induced cortical inhibition.

How long does it take for antidepressant therapies to act?

OBJECTIVE: To review the proposition that antidepressants have a delayed onset of action by employing measurement and analytic strategies that overcome problems confounding interpretation of many efficacy studies. METHOD: A subset of patients was recruited to the longitudinal component of the Australasian database study, was assessed at baseline, and then completed measures of depression and anxiety when treatment commenced, and every 3 days over the next 4 weeks. The trajectories of defined 4-week outcome responders and non-responders were compared. RESULTS: Both groups showed a similar decrease in depression (and anxiety) over the first 3 days. A clear trend break then occurred, with little further improvement in the non-responders, as against distinct and progressive improvement in the responders. Ongoing early improvement (across days 3-6) was a strong predictor of responder status. CONCLUSIONS: The small sample size limits firm interpretation, although distinct interpretive advantages to the study design are evident. Findings are compatible with a number of recent studies arguing against any extensive delayed onset of action for the antidepressant drugs, but argue for caution in interpreting immediate improvement as predicting likely responder status, and more for examining early and sustained improvement as such a marker.