Epilepsy: Efficacy of epilepsy surgery: what are the questions today?

Consistent with previous findings, two recent studies of temporal lobectomy from Kerala, India demonstrate that early seizure recurrence bodes poorly for long-term seizure control, and that relapse following drug discontinuation affects one-third of patients. Key questions in the field now concern advanced preoperative and intraoperative techniques for improving surgical outcomes.     

CTOs: what is the state of the evidence?

Purpose

Community Treatment Orders (CTOs) require outpatients to adhere to treatment and permit rapid hospitalisation when necessary. They have become a clinical and policy solution to repeated hospital readmissions despite some strong opposition and the contested nature of published evidence. In this article, we appraise the current literature on CTOs from the viewpoint of Evidence-Based Medicine and discuss the way forward for using and researching CTOs.

Results

Non-randomised outcome studies show conflicting results, but their lack of standardisation of methods and measures makes it difficult to draw conclusions. In contrast, all three randomised controlled trials (RCTs) conducted concur in their findings that CTOs do not impact on hospital outcomes. No systematic review or meta-analysis has identified any clear clinical advantage to CTOs.

Conclusion

The evidence-base does not support the use of CTOs in their current form. Involuntary clinical interventions must conform to the highest standard of evidence-based care. To enable clinicians to take an evidence-based approach and to settle remaining uncertainties about the current evidence, high-quality RCTs should be designed and undertaken, using standardised outcome measures.     

Psychological therapy in schizophrenia: what is the evidence?

OBJECTIVE: The present contribution provides a critical outline of the current position of psychological therapies in schizophrenia. METHOD: Therefore, empirical research into the efficacy of psychological interventions in the treatment of schizophrenic disorders has been reviewed. RESULTS: Four cognitive-behavioural approaches have emerged as preeminently effective, or at least especially promising, as adjuncts to pharmacotherapy, i.e. the training of social skills, cognitive training programs for the remediation of neurocognitive deficits, psychoeducative, coping-orientated interventions with patients and their families, and cognitive-behavioural therapy of residual symptoms. These approaches are discussed with regard to their efficacy in reducing relapse rates, psychopathology as well as cognitive and social disability. CONCLUSION: Open questions and possibilities for the further development of these approaches are considered and prognostications are made concerning the future of psychotherapy research in schizophrenia, notably in the light of changing conditions in public health care systems.     

Prospective studies of suicidal behavior in major depressive and bipolar disorders: what is the evidence for predictive risk factors?

OBJECTIVE: Prospective studies over the past 30 years have identified an array of predictive indicators for suicidal acts in mood disorders. However, prediction of suicidal behavior remains an elusive goal. This paper reviewed evidence from prospective studies for clinical factors that elevate risk of suicidal acts in that group. METHOD: English language prospective studies of suicidal behavior in major depressive and bipolar disorders were examined. RESULTS: The predictors with the best support were a past history of suicidal behavior and the presence of refractory or recurrent depressions. For other risk factors, there was either not enough data to consider them robust or findings were contradictory. CONCLUSION: Future studies must not only be comprehensive in their inclusion of potentially contributing factors, but must also address their relative importance towards the goal of developing predictive models and enhance suicide prevention efforts.     

Neurological complications of coeliac disease: what is the evidence?

Coeliac disease is a chronic immune-mediated disorder that primarily affects the gastrointestinal tract. There is an inflammatory response in the intestine to the ingestion of gluten which improves with a gluten-free diet. Many patients, especially adults, may be asymptomatic or have only extraintestinal symptoms at onset without any of the classical coeliac symptoms. In the last two decades there have been increasing numbers of reports describing neurological complications of coeliac disease, especially ataxia, peripheral neuropathy and epilepsy. This literature has become quite controversial, with disputes over the definition of coeliac disease and gluten sensitivity, whether neurological complications are caused by coeliac disease or are epiphenomena, and whether the proposed complications respond to a gluten-free diet. This review uses an evidence-based approach to critically assess this literature and provides guidelines for the evaluation and management of these patients.     

The role of excitotoxicity in ALS – what is the evidence?

It is well accepted that excitotoxic mechanisms contribute to the pathogenesis of acute neuronal death in stroke, epilepsy, or brain trauma. It is less widely acknowledged that excitotoxic mechanisms play a role in the pathogenesis of chronic neurological disorders, in particular neurodegenerative diseases. However, evidence is accumulating that this mechanism is indeed part of the pathogenesis of late-onset neurodegenerative diseases. One of the clinical examples may be amyotrophic lateral sclerosis, a disease in which antiexcitotoxic strategies have neuroprotective effects in both, an established animal model and in man. In addition, there is accumulating neuropathological, pathobiochemical and pathophysiological evidence which indicates that excitotoxic mechanisms are part of the pathogenesis of the human disease and consequently part of the mechanisms explaining selective vulnerability (“pathoclisis”) in the human motor system.

     

The role of neurotensin in central nervous system pathophysiology: what is the evidence?

The peptide neurotensin has been studied for more than 30 years. Although it is widely distributed in the central and peripheral nervous systems, neurotensin has been more intensely studied with regard to its interactions with the central dopamine system. A number of claims have been made regarding its possible implication in many diseases of the central nervous system, including schizophrenia. In this review, we describe briefly the basic biology of this neuropeptide, and then we consider the strengths and the weaknesses of the data that suggest a role for neurotensin in schizophrenia, drug abuse, Parkinson's disease, pain, central control of blood pressure, eating disorders, cancer, neurodegenerative disorders and inflammation.     

Aberrant folate status in schizophrenic patients: what is the evidence?

A vast amount of case reports, open studies and, to a lesser extent, case-control studies have been published on the topic of psychopathology and folate deficiency. These studies reported a high incidence of serum folate deficiency in patients with various psychiatric disorders. Folate deficiency seems to be a particular consistent finding in depressive patients. The evidence for an association between aberrant folate status and schizophrenia seems less convincing. The lack of stringent methodology such as inclusion of age- and sex-matched controls was thought to be the main reason for the inconclusive results. The purpose of this article is to review the published case-control studies that provide data on folate levels in the population of patients with schizophrenia. Data extracted from these studies comprised methodological design, clinical characteristics and folate measurements. We found that none of the 7 case-control studies included in this review (in total 325 cases and 560 control subjects) explicitly reported on all critical factors in the assessment of folate. In addition, only three studies found lower plasma folate levels more frequently in patients with schizophrenia compared to controls. Further research on this topic is required to clarify the relationship between folate status and schizophrenia and should avoid the methodological pitfalls mentioned in this review. In addition, research should also focus on polymorphisms of genes related to folate metabolism.     

Treating minority patients with depression and anxiety: what does the evidence tell us?

OBJECTIVE: The purpose of this study is to examine the current state of knowledge regarding treating ethnic/racial minority patients with mood and anxiety disorders, emphasizing data-based studies whenever possible. METHOD: This article reviews the evidence on poorer access and quality of care for minorities, the biological and cultural differences between minority and majority populations that may impact care and outcomes, and recent studies that address minority treatment response and outcomes both alone and in comparison to majority groups. RESULTS: Numerous impediments to appropriately treating anxious and depressed minority patients remain. Underutilization and poor quality of mental health care in minorities is due to less-than-favorable illness and treatment beliefs that affect adherence and outcome, stigma, clinician failure to engage the patient, poor patient activation and biological differences that may impact pharmacotherapy choice. However, though limited in number, some studies do indicate that when appropriate treatment is well-delivered to minorities, results are comparable to those seen among Caucasian patients. CONCLUSIONS: The clinician treating members of minority groups must consider differential personal elements, from the biological to the cultural, to achieve treatment success. The limited available data do suggest that minority patients can be successfully treated with available interventions. Of primary importance is for researchers to increase the number of carefully designed intervention studies that allow for ethnic/racial minority-specific analyses.     

Bleeding and thrombosis in acute leukemia: what does the future of therapy look like?

Bleeding and thrombosis are major risk factors for early death in patients with acute leukemia; chemotherapy increases the likelihood of both of these complications. Patients with acute leukemia often present with a hypercoagulable state or with evidence for chronic disseminated intravascular coagulation, even in the absence of active thrombosis and/or bleeding. Leukemic cell procoagulant properties, cytotoxic therapies, and concomitant infections are major determinants of clotting activation in acute leukemia. Clinical manifestations range from localized venous or arterial thrombosis to diffuse life-threatening bleeding. All-trans retinoic acid has greatly improved the management of acute promyelocytic leukemia, but has not significantly changed the rate of early hemorrhagic deaths and may actually promote thrombosis. Randomized, controlled trials of different prophylactic regimens to prevent thrombosis and/or bleeding in acute leukemia are urgently needed, particularly in patients with acute promyelocytic leukemia. Anticoagulant therapy is a unique challenge in patients with acute leukemia, who are at high risk for hemorrhage. Although no guidelines are available for prophylaxis or treatment of thrombosis, extrapolation can be made from existing guidelines for management of patients with other malignancies prolonged periods of treatment-induced thrombocytopenia in patients with acute leukemia, however, require a more judicious application of standard anticoagulant approaches. Use of the newer anticoagulants will require careful assessment of hemorrhagic risk in this group of high risk patients but may be justified under special circumstances.