Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: A meta-analysis of placebo-controlled trials

Background

The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo.

Methods

A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990–2012, was performed using the terms ‘atypical antipsychotics’, ‘SGA’, ‘mixed episodes’, ‘dysphoric mania’ and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3–6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit.

Results

SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (−0.41, 95% CI −0.53, −0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (−0.30, 95% CI −0.47, −0.13; p<0.001) compared to placebo in two trials reporting this information.

Limitations

Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately.

Conclusions

SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.     

Comparison of facemask and mouthpiece interfaces for multiple breath washout measurements

Background

Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children.

Double-blind randomized controlled study showing symptomatic and cognitive superiority of bifrontal over bitemporal electrode placement during electroconvulsive therapy for schizophrenia

BackgroundSeveral studies show that bifrontal electrode placement produces relatively fewer cognitive adverse effects than bitemporal placement during electroconvulsive therapy (ECT) in depression. There are no reports comparing these electrode placements in schizophrenia.ObjectivesThis study compared the clinical and cognitive effects of bifrontal and bitemporal electrode placements in schizophrenia patients referred for electroconvulsive therapy (ECT).Methods122 schizophrenia patients who were prescribed ECT were randomized to receive ECT with either bifrontal (BFECT; n = 62) or bitemporal (BTECT; n = 60) placement. Their concomitant anti-psychotic medications and the number of ECT sessions were not controlled. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS), Bush-Francis Catatonia Rating Scale (BFCRS), and the Nurse Observation Scale for Inpatient Evaluation (NOSIE). Cognitive functions were assessed 24-h after the final ECT using a battery of tests. Clinical improvement was compared using chi-square test, repeated measures ANOVA and analysis of covariance (ANCOVA). Cognitive adverse effects were compared using t-test.ResultsAt the end of 2 weeks (after 6 ECT sessions) 63% and 13.2% of BFECT and BTECT patients respectively had met the response criterion for BPRS (40% reduction in total score; OR = 20.8; 95% CI = 3.61–34.33). BFECT patients showed significantly faster clinical response on BPRS (Time × Group interaction effect: P = 0.001), BFCRS (P < 0.001) and the NOSIE total assets score (P = 0.003). ANCOVA using baseline scores as covariates and treatment-resistance status as between-subject factor showed that BFECT patients had significantly greater improvement in all measures. BFECT patients had significantly higher PGI-memory-scale total score than BTECT patients (t = 5.16; P < 0.001). They also showed superior performance in other cognitive measures.ConclusionsBFECT results in superior clinical and cognitive outcomes than BTECT in schizophrenia patients referred for ECT.     

Muscle function and resting energy expenditure in female athletes with cystic fibrosis

The pathophysiology of impaired exercise tolerance in patients with cystic fibrosis (CF) is not completely understood. The objective of this study was to compare exercise ability (at clinical and cellular levels) and resting energy expenditure in female athletes with CF compared with matched control subjects. Sixteen subjects and matched control subjects participated in the study. The girls with CF not only had a significantly greater resting energy expenditure (7.6% higher; p<0.05), their habitual daily activity was also significantly greater than that of control subjects (15% greater; p<0.01). Peak aerobic capacity was similar in both groups. However, peak anaerobic power was 20% less (p<0.05) in girls with CF. The 31P magnetic resonance spectroscopy studies demonstrated that there were no differences between the groups at rest, but at 25% total work output the girls with CF were less acidotic (CF, pH 6.99 [0.06]; control subjects, 6.90 [0.05]) and had a significantly lower inorganic phosphorus-to-phosphocreatine ratio (CF, 0.34 [0.07]; control subjects, 0.41 [0.08]). These differences continued to increase to maximal exercise. This study demonstrates that in spite of normal lung function and good nutritional status, females athletes with CF still had significant deficiencies in some measures of fitness and muscle metabolism compared with healthy athletes.     

Our experience with aortic root replacement using hand-sewn composite valve graft

Background The purpose of this study is to examine our experience with aortic root replacement using composite valve grafts in patients with proximal aortic disease. Methods and Results Since 1986, 16 patients underwent aortic root replacement using composite valve grafts for various indications which were Marfan's syndrome with annuloaortic ectasia (n=2), aortic regurgitation with ascending aortic aneurysm (n=3), aortic stenosis with regurgitation with poststenotic dilatation (n=9) and progressive aortic dilatation following AVR (n=2). There were 12 males and 4 females. The age range varied between 19 years and 52 years. The choice of conduit was a custom made valved graft using a monoleaflet tilting disc valve (Medtronic Hall valve=11, St Vincent's valve=3, TTK Chitra=1 and Bjork Shiley Valve=1) placed in a Dacron graft (Hemashield=13, Verisoft Cooley=3) prepared using a 4-0 polypropylene suture. The average time taken to construct a valved graft was 20 min±8 min. The coronary implantation was by isolated button technique. There was no size mismatch encountered in any patients. Postoperative bleeding necessitated a delayed sternal closure in 3 patients and re-exploration in another 2. The immediate operative mortality was 2, the cause being ventricular arrhythmia in one and cerebrovascular accident in other. Follow-up period ranged from 2 months to 16 years with a median follow-up of 12 months. One patient had an asymptomatic perigraft collection and no intervention was needed. There was no valve related complications in any of these patients. There was one late death of unknown cause. Conclusions Aortic root replacement using a custom made composite graft offers excellent long-term results, with negligible mortality rate and prosthesis related complications. Custom made grafts make this conduit easily affordable in our country and their performance is comparable to other available composite grafts.     

Paediatric retropharyngeal abscess

Retropharyngeal abscess (RPA) is an uncommon condition with the potential for significant morbidity and mortality if not detected early. The authors present a case report of a 19-month-old child who presented with the common clinical features of a retropharyngeal abscess and in whom the diagnosis was not established by examination and ultrasonography. This led to a delay in appropriate management until a computed tomography (CT) scan was performed under general anaesthesia. The scan demonstrated the diagnosis and surgical drainage was performed under the same anaesthetic. The child subsequently made a complete recovery. The investigation and treatment of RPAs is a matter of some debate and the authors review the recent literature to determine the best management strategy.