Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.

Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.

Does a medicinal dose of kava impair driving? A randomized, placebo-controlled, double-blind study.

OVERVIEW: Increasing concerns over the potentially impairing effects of prescriptive sedative drugs such as benzodiazepines on driving have been raised. However, other alternatives such as natural medicines may also carry similar risks with respect to driving safety. Kava (Piper methysticum) is a psychotropic plant commonly used both recreationally and medicinally in the United States, Australia, and the South Pacific to elicit a physically tranquilizing effect. To date no controlled study has tested a medicinal dose of kava versus placebo and a standard sedative drug on driving ability and driving safety. OBJECTIVE: Due to the need to establish the safety of kava in operating a motor vehicle, we compared the acute effects of the plant extract versus the benzodiazepine oxazepam and placebo using a driving simulator. METHODS: A driving simulator (AusEd) was used by 22 adults aged between 18 and 65 years after being randomly administered an acute medicinal dose of kava (180 mg of kavalactones), oxazepam (30 mg), or placebo one week apart in a crossover design trial. RESULTS: No impairing effects on driving outcomes were found after kava administration compared to placebo. Results on specific driving outcome domains revealed that the oxazepam condition had significantly slower braking reaction time compared to the placebo condition (p =.002) and the kava condition (p =.003). The kava condition had significantly fewer lapses of concentration compared to the oxazepam condition (p =.033). No significant differences were found between conditions for steering deviation, speed deviation, and number of crashes. Results were not modified by driving experience. On the Bond-Lader visual analogue sub-scale of alertness, a significant Treatment × Time interaction (p =.032) was found, with a significant reduction over time for oxazepam decreasing alertness (p <.001), whereas no significant reduction was found in the kava or placebo conditions. CONCLUSION: The results indicate that a medicinal dose of kava containing 180 mg of kavalactones does not impair driving ability, whereas 30 mg of oxazepam shows some impairment. Research assessing larger recreational doses of kava on driving ability should now be conducted.

Complementary medicine, exercise, meditation, diet, and lifestyle modification for anxiety disorders: a review of current evidence.

Use of complementary medicines and therapies (CAM) and modification of lifestyle factors such as physical activity, exercise, and diet are being increasingly considered as potential therapeutic options for anxiety disorders. The objective of this metareview was to examine evidence across a broad range of CAM and lifestyle interventions in the treatment of anxiety disorders. In early 2012 we conducted a literature search of PubMed, Scopus, CINAHL, Web of Science, PsycInfo, and the Cochrane Library, for key studies, systematic reviews, and metaanalyses in the area. Our paper found that in respect to treatment of generalized anxiety or specific disorders, CAM evidence revealed current support for the herbal medicine Kava. One isolated study shows benefit for naturopathic medicine, whereas acupuncture, yoga, and Tai chi have tentative supportive evidence, which is hampered by overall poor methodology. The breadth of evidence does not support homeopathy for treating anxiety. Strong support exists for lifestyle modifications including adoption of moderate exercise and mindfulness meditation, whereas dietary improvement, avoidance of caffeine, alcohol, and nicotine offer encouraging preliminary data. In conclusion, certain lifestyle modifications and some CAMs may provide a beneficial role in the treatment of anxiety disorders.

St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT.

Hypericum perforatum (St John's wort: SJW) has been extensively studied as an antidepressant in short-term trials, however little research has been conducted on longer-term efficacy.Our objective was to analyze the continuation data from a 26-week randomized, double-blind, controlled study of SJW (LI-160) vs. sertraline and placebo in major depressive disorder. 124 participant "responders" continued treatment after week 8, until week 26. They continued randomly assigned SJW (900-1 500 mg), sertraline (50-100 mg) or matching placebo.At week 26, on the primary outcome, Hamilton depression rating scale (HAM-D) completer scores were: SJW (6.6±4.5), sertraline (7.1±5.4) and placebo (5.7±5.4) with a significant effect for time (p=0.036). Comparisons between all treatments were however non-significant (p=0.61). This effect was mirrored on the other outcomes: the BDI, CGI-severity, CGI-improvement, and on intention-to-treat analyses.While the continuation data revealed an equivocal outcome between treatments at week 26, both SJW and sertraline were still therapeutically effective, with a pronounced "placebo-effect" impeding a significant result at week 26.

The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study.

RATIONALE: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines. METHODS: Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial. RESULTS: After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial ŋ² = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava. CONCLUSION: Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition.

Should bipolar disorder be viewed as manic disorder? Implications for bipolar depression.

This paper proposes that the syndrome of mania rather than mood swings is the central distinguishing feature of bipolar disorder, which may be more appropriately viewed as manic disorder. The theoretical consequence of this change in perspective is to regard the depressive mood states as being a co-morbid condition. This may lead to a more profound and broader understanding of the variety of states of depression that complicate manic disorder. The paper also reviews diagnostic issues relating to bipolar depression. A broader approach may extend therapeutic choices, and open innovative research avenues.

Antiglaucoma medication and clinical depression.

OBJECTIVE: The aim of this paper is to alert the medical community to the potential risk of clinical depression following the use of antiglaucoma medication. METHOD: The available literature concerning systemic side-effects of topical antiglaucoma medication and the association of these agents with clinical depression were reviewed. In addition, two cases are reported of the occurrence of clinical depression following use of topical betaxolol which only resolved completely after switching glaucoma medication. RESULTS/CONCLUSIONS: The case reports presented here add to the increasing body of literature linking topical ophthalmic beta-adrenoceptor antagonists with depression. While these cases are uncommon, this phenomenon continues to be poorly recognized by the medical profession, psychiatrists, ophthalmologists and general practitioners alike.

Evaluating complex, collaborative programmes: the Partnership Project as a case study.

OBJECTIVE: In Australia, mental health services are delivered by a complex web of public- and private-sector providers. There is a growing recognition that linkages between these groups are not optimal, and a concern that this may lead to poor outcomes. This paper illustrates a conceptual framework for developing, implementing and evaluating programmes concerned with linkages. METHOD: Drawing on theoretical and practical literature, this paper identifies different levels of integration, issues in evaluating programmes to address poor linkages, and features of useful evaluations. Within this context, it describes the method by which the Public and Private Partnerships in Mental Health Project (Partnership Project) is being evaluated. Conducted by St Vincent's Mental Health Service and The Melbourne Clinic, this is one of several Demonstration Projects in Integrated Mental Health Care funded under the National Mental Health Strategy. RESULTS: Collaboration is hard to conceptualize and collaborative programmes usually have many players and components, and tend to operate within already-complex systems. This creates difficulties for evaluation, in terms of what to measure, how to measure it, and how to interpret findings. In spite of these difficulties, the illustrative example demonstrates a model for evaluating collaborative programmes that is currently working well because it is strongly conceptualized, descriptive, comparative, constructively sceptical, positioned from the bottom up, and collaborative. CONCLUSIONS: This model, or aspects of it, could be extended to the evaluation of other mental health programmes and services that have collaborative elements.

Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls.

OBJECTIVE: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. METHODS: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. RESULTS: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. CONCLUSION: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

Do blood transfusions improve outcomes related to mechanical ventilation?

BACKGROUND: Correcting the decrease in oxygen delivery from anemia using allogeneic RBC transfusions has been hypothesized to help with increased oxygen demands during weaning from mechanical ventilation. However, it is also possible that transfusions hinder the process because RBCs may not be able to adequately increase oxygen delivery. In this study, we determined whether a liberal RBC transfusion strategy improved outcomes related to mechanical ventilation. METHODS: Seven hundred thirteen patients receiving mechanical ventilation, representing a subgroup of patients from a larger trial, were randomized to either a restrictive transfusion strategy, receiving allogeneic RBC transfusions at a hemoglobin concentration of 7.0 g/dL (and maintained between 7.0 g/dL and to 9.0 g/dL), or to a liberal transfusion strategy, receiving RBCs at 10.0 g/dL (and maintained between 10.0 g/dL and 12.0 g/dL). The larger trial was designed to evaluate transfusion practice rather than weaning per se. RESULTS: Baseline characteristics in the restrictive-strategy group (n = 357) and the liberal-strategy group (n = 356) were comparable. The average durations of mechanical ventilation were 8.3 +/- 8.1 days and 8.3 +/- 8.1 days (95% confidence interval [CI] around difference, - 0.79 to 1.68; p = 0.48), while ventilator-free days were 17.5 +/- 10.9 days and 16.1 +/- 11.4 days (95% CI around difference, - 3.07 to 0.21; p = 0.09) in the restrictive-strategy group vs the liberal-strategy group, respectively. Eighty-two percent of the patients in the restrictive-strategy group were considered successfully weaned and extubated for at least 24 h, compared to 78% for the liberal-strategy group (p = 0.19). The relative risk (RR) of extubation success in the restrictive-strategy group compared to the liberal-strategy group, adjusted for the confounding effects of age, APACHE (acute physiology and chronic health evaluation) II score, and comorbid illness, was 1.07 (95% CI, 0.96 to 1.26; p = 0.43). The adjusted RR of extubation success associated with restrictive transfusion in the 219 patients who received mechanical ventilation for > 7 days was 1.1 (95% CI, 0.84 to 1.45; p = 0.47). CONCLUSION: In this study, there was no evidence that a liberal RBC transfusion strategy decreased the duration of mechanical ventilation in a heterogeneous population of critically ill patients.

Sustained response to open-label venlafaxine in drug-resistant major depression.

The aim of this study was to evaluate the response to venlafaxine in patients with treatment-resistant depression during an extension phase of an open-label study of venlafaxine. After completing the initial 8 weeks of the study, patients could continue venlafaxine treatment for an additional period of up to 10 months. Efficacy results are given for 149 patients with treatment-resistant depression. Response was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale (MADRS); 69% were responders after 8 weeks of treatment in the initial study phase, and 73% were responders at their final extension-phase visit. The mean MADRS score was 32.8 before treatment, 12.9 by 8 weeks, and 10.8 at the final extension visit. There was a statistically significant reduction of 2.1 MADRS units from entry into the extension phase to the final extension visit. At extension entry, 36.7% patients were in remission, as defined by a MADRS score of less than 12, whereas at the final extension visit, this had increased to 49%. Improvement in Clinical Global Impressions Scale scores (both patient and physician ratings) was maintained throughout the extension period, with 88% of patients reporting some improvement (75% with "very much" or "much") and 92% of doctors noting some improvement in patients (79% with "very much" or "much") at the last extension visit. The safety profile during the extension phase of the study was similar to that found in the initial phase and in other studies. The most common study events were somnolence (21%), headache (18%), insomnia (16%), sweating (16%), constipation (14%), dry mouth (11%), nausea (10%), and dizziness (10%). Patients with resistant depression that was treated with venlafaxine maintained their response for up to 10 months after an 8-week phase of treatment and showed some evidence of further improvement.

Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?

OBJECTIVE: To compare a restrictive red blood cell transfusion strategy with a more liberal strategy in volume-resuscitated critically ill patients with cardiovascular disease. SETTING: Twenty-two academic and three community critical care units across Canada. STUDY DESIGN: Randomized controlled clinical trial. STUDY POPULATION: Three hundred fifty-seven critically ill patients with cardiovascular diseases from the Transfusion Requirements in Critical Care trial who had a hemoglobin concentration of <90 g/L within 72 hrs of admission to the intensive care unit. INTERVENTIONS: Patients were randomized to a restrictive strategy to receive allogeneic red blood cell transfusions at a hemoglobin concentration of 70 g/L (and maintained between 70 and 90 g/L) or a liberal strategy to receive red blood cells at 100 g/L (and maintained between 100 and 120 g/L). RESULTS: Baseline characteristics in the restrictive (n = 160) and the liberal group (n = 197) were comparable, except for the use of cardiac and anesthetic drugs (p <.02). Average hemoglobin concentrations (85 +/- 6.2 vs. 103 +/- 6.7 g/L; p <.01) and red blood cell units transfused (2.4 +/- 4.1 vs. 5.2 +/- 5.0 red blood cell units; p <.01) were significantly lower in the restrictive compared with the liberal group. Overall, all mortality rates were similar in both study groups, including 30-day (23% vs. 23%; p = 1.00), 60-day, hospital, and intensive care unit rates. Changes in multiple organ dysfunction from baseline scores were significantly less in the restrictive transfusion group overall (0.2 +/- 4.2 vs. 1.3 +/- 4.4; p =.02). In the 257 patients with severe ischemic heart disease, there were no statistically significant differences in all survival measures, but this is the only subgroup where the restrictive group had lower but nonsignificant absolute survival rates compared with the patients in the liberal group. CONCLUSION: A restrictive red blood cell transfusion strategy generally appears to be safe in most critically ill patients with cardiovascular disease, with the possible exception of patients with acute myocardial infarcts and unstable angina.

Does risperidone have a place in the treatment of nonschizophrenic patients?

There is a now a substantial body of evidence that suggests the new antipsychotic agent, risperidone, may be safe and effective for treating psychotic, affective or behavioural symptoms associated with various disorders other than schizophrenia, schizophreniform disorder or schizo-affective disorder. These conditions include bipolar disorder, obsessive-compulsive disorder, Tourette's syndrome, dementia, Lewy body disease, mental retardation, Parkinson's disease, idiopathic segmental dystonia and organic catatonia. Although much of the data is anecdotal or in the form of open studies, there is now emerging a small number of well controlled investigations supporting efficacy for mania, dementia, behavioural disturbance in mental retardation and conduct disorder. Conventional antipsychotics have long been used, either in a primary capacity or as an adjunct to treat these disorders; however, they have limited benefit, pose significant risks of extrapyramidal side-effects, and may cause the potentially life-threatening neuroleptic malignant syndrome. In contrast, risperidone at the recommended low doses may be efficacious and pose reduced risk of motor side-effects. This article reviews the evidence that risperidone may be an effective new treatment for disorders other than schizophrenia.

The impact of reduced frequency of cage changes on the health of mice housed in ventilated cages.

Our purpose in this investigation was to determine if we could reduce cage changing frequency without adversely affecting the health of mice. We housed mice at three different cage changing frequencies: 7, 14, and 21 days, each at three different cage ventilation rates: 30, 60 and 100 air changes per hour (ACH), for a total of nine experimental conditions. For each condition, we evaluated the health of 12 breeding pairs and 12 breeding trios of C57BL/6J mice for 7 months. Health was assessed by breeding performance, weanling weight and growth, plasma corticosterone levels, immune function, and histological examination of selected organs. Over a period of 4 months, we monitored the cage microenvironment for ammonia and carbon dioxide concentrations, relative humidity, and temperature one day prior to changing the cage. The relative humidity, carbon dioxide concentrations, and temperature of the cages at all conditions were within acceptable levels. Ammonia concentrations remained below 25 ppm (parts per million) in most cages, but, even at higher concentrations, did not adversely affect the health of mice. Frequency of cage changing had only one significant effect; pup mortality with pair matings was greater at the cage changing frequency of 7 days compared with 14 or 21 days. In addition, pup mortality with pair matings was higher at 30 ACH compared with other ventilation rates. In conclusion, under the conditions of this study, cage changes once every 14 days and ventilation rates of 60 ACH provide optimum conditions for animal health and practical husbandry.

Personality pathology, depression and HPA axis functioning.

Hypothalamic pituitary adrenal (HPA) axis functioning, as measured by the dexamethasone suppression test (DST), has been extensively investigated in major depressive disorder (MDD). Evaluating DST response in MDD patients while simultaneously considering clinically relevant personality disorders may further clarify the contribution of both personality pathology and HPA axis function to depressive symptoms. The present study measured personality pathology by administering the revised version of the Millon Clinical Multiaxial Inventory (MCMI-II) in a sample of 25 patients diagnosed with MDD. Analyses revealed that suppressors (n = 19) scored significantly higher than non-suppressors (n = 6) on six of the 13 MCMI-II personality disorder scales: Avoidant, Schizoid, Self-Defeating, Passive-Aggressive, Schizotypal and Borderline. Increased personality pathology was associated with normal suppression of cortisol following the DST. This suggests that suppression of the DST may be associated with depressive states linked with personality pathology while the more biologically based depression is associated with abnormal HPA pathophysiology. Copyright 2001 John Wiley & Sons, Ltd.

Structural neuroimaging studies in late-life depression: a review.

Which patients presenting with depression in late life will progress to a dementia syndrome has been an important research question in recent times. In this paper we review selectively structural neuroimaging investigations of late-life depression (LLD) that have been performed over the past two decades. These studies indicate that there are neuroimaging changes commonly observed in LLD patients when compared to normal controls. Findings include ventricular enlargement and sulcal widening, and reduction in volume size of frontal lobes, hippocampus and caudate nucleus. White matter lesions are more common in depressed subjects and tend to be more severe. Some studies report these changes to be more pronounced in patients who present with late-onset depression (LOD) but this has been contradicted by other studies. Preliminary work suggests that these changes may be associated with a poor prognosis but there is a dearth of systematic, well-controlled longitudinal studies.

Efficacy of venlafaxine and predictors of response in a prospective open-label study of patients with treatment-resistant major depression.

The aim of this study was to replicate the findings of a 1994 study, in which a 30% response rate to venlafaxine was found in patients with treatment-refractory depression, as well as to examine for any predictors of such an outcome. The study was an 8-week, open-label, prospective investigation of venlafaxine in doses up to 300 mg in 312 patients fulfilling criteria for either "absolute" or "relative" treatment resistance. By week 8, 52.6% of the patients had responded, which was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale; 49% of those defined with "absolute resistance" demonstrated such an outcome. Forty-five percent of the patients with absolute resistance who had failed to respond to at least one tricyclic antidepressant responded to venlafaxine. Response rates were higher in those with an absence (57.5%) compared with the presence (31.0%) of any comorbid psychiatric disorder (p < 0.001), "marked" (60.3%) compared with "mild or moderate" (51.6%) or "severe" (43.4%) baseline ratings on the patient-rated Clinical Global Impressions Scale (p < 0.05), and "relative" (61%) compared with "absolute" resistance (49%) (p = 0.06). Furthermore, improvement in scores of 20% or 30% at weeks 1 or 2 was associated with higher rates of final response (p < 0.0005). After logistic regression, both comorbid psychiatric illness (p < 0.001) and early improvement (p < 0.0001) remained significant and independent predictors of final response.

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.

Efficacy and cognitive effects of right unilateral electroconvulsive therapy.

The efficacy, memory, and cognitive effects of right unilateral (RUL) electroconvulsive therapy (ECT) at 2.5 times threshold in 32 inpatients with moderate to severe major depressive disorder were evaluated at baseline, during the course of treatment, and 1 month after treatment. Neuropsychological assessment included the Randt Memory Test, Personal Memory Test, short-version Wechsler Adult Intelligence Scale-Revised, and Self-Rating Scale of Memory Functions. At the treatment end point, although the Hamilton Depression Rating Scale mean score was decreased by 54.2%. the response rate of 2.5 times threshold RUL ECT using stringent criteria was only 31.2%. Treatment was associated with significant anterograde memory impairment in the short term. Mean total scores of the Randt Memory Test and Personal Memory Test were decreased from baseline by 14.8% and 32.5%, respectively, after six sessions of ECT. These memory deficits were significantly improved by the 1 month follow-up examination. Subjective memory scores increased consistently during treatment, correlating with improvements in mood. No adverse effects on nonmemory cognition were found. Although RUL ECT at 2.5 times threshold is not associated with marked or persistent cognitive disturbances, its efficacy may be insufficient in clinical practice.

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

BACKGROUND: To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS: We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS: Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.