Anxiety sensitivity as a predictor of broad dimensions of psychopathology after cognitive behavioral therapy for panic disorder

Background: Panic disorder (PD) is a common disease and presents with broad dimensions of psychopathology. Cognitive behavioral therapy (CBT) is known to improve these broad dimensions of psychopathology in addition to PD symptoms. However, little is known about the predictors of treatment response in comorbid psychiatric symptoms after CBT for PD. Recent studies suggest that anxiety sensitivity (AS) may be a key vulnerability for PD. This study aimed to examine AS as a predictor of broad dimensions of psychopathology after CBT for PD. Materials and methods: In total, 118 patients with PD were treated with manualized group CBT. We used multiple regression analysis to examine the associations between 3 Anxiety Sensitivity Index (ASI) factors (physical concerns, mental incapacitation concerns, and social concerns) at baseline and the subscales of the Symptom Checklist-90 Revised (SCL-90-R) at endpoint. Results: Low levels of social concerns at baseline predicted low levels on 5 SCL-90-R subscales after CBT: interpersonal sensitivity, depression, hostility, paranoid ideation, and psychosis. High levels of mental incapacitation concerns significantly predicted low levels on 3 SCL-90-R subscales after treatment: interpersonal sensitivity, hostility, and paranoid ideation. Physical concerns at baseline did not predict broad dimensions of psychopathology. Conclusion: This study suggested that the social concerns and mental incapacitation concerns subscales of the ASI at baseline predicted several dimensions of psychopathology after CBT for PD. To improve comorbid psychopathology, it may be useful to direct more attention to these ASI subscales

A Disseminated Fusarium fujikuroi Species Complex Infection Prior to Allogeneic Hematopoietic Stem Cell Transplantation

A 53-year-old man was diagnosed with acute myeloid leukemia, which was refractory to chemotherapies. Systemic papules appeared afterward. The skin biopsies revealed filamentous fungal infection including fusariosis. Despite antifungal therapy, the infection did not resolve, because neutropenia persisted with the leukemia. He underwent hematopoietic stem cell transplantation (HSCT) to overcome the leukemia and restore normal hematopoiesis but died from fusariosis just before engraftment. Fusarium fujikuroi species complex was detected in blood cultures with poor antifungal susceptibility. Because restoring normal hematopoiesis is important in the treatment of fusariosis, HSCT might be considered for patients with persistent pancytopenia

A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery

A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis

Dismantling cognitive-behaviour therapy for panic disorder: a systematic review and component network meta-analysis.

Cognitive-behaviour therapy (CBT) for panic disorder may consist of different combinations of several therapeutic components such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure and/or in vivo exposure. It is therefore important both theoretically and clinically to examine whether specific components of CBT or their combinations are superior to others in the treatment of panic disorder. Component network meta-analysis (NMA) is an extension of standard NMA that can be used to disentangle the treatment effects of different components included in composite interventions. We searched MEDLINE, EMBASE, PsycINFO and Cochrane Central, with supplementary searches of reference lists and clinical trial registries, for all randomized controlled trials comparing different CBT-based psychological therapies for panic disorder with each other or with control interventions. We applied component NMA to disentangle the treatment effects of different components included in these interventions. After reviewing 2526 references, we included 72 studies with 4064 participants. Interoceptive exposure and face-to-face setting were associated with better treatment efficacy and acceptability. Muscle relaxation and virtual-reality exposure were associated with significantly lower efficacy. Components such as breathing retraining and in vivo exposure appeared to improve treatment acceptability while having small effects on efficacy. The comparison of the most v. the least efficacious combination, both of which may be provided as 'evidence-based CBT,' yielded an odds ratio for the remission of 7.69 (95% credible interval: 1.75 to 33.33). Effective CBT packages for panic disorder would include face-to-face and interoceptive exposure components, while excluding muscle relaxation and virtual-reality exposure

Overstatements in abstract conclusions claiming effectiveness of interventions in psychiatry: A study protocol for a meta-epidemiological investigation

Introduction: Abstracts are the major and often the most important source of information for readers of the medical literature. However, there is mounting criticism that abstracts often exaggerate the positive findings and emphasise the beneficial effects of intervention beyond the actual findings mentioned in the corresponding full texts. In order to examine the magnitude of this problem, we will introduce a systematic approach to detect overstated abstracts and to quantify the extent of their prevalence in published randomised controlled trials (RCTs) in the field of psychiatry. Methods and analysis: We will source RCTs published in 2014 from the Cochrane Register of Controlled Trials (CENTRAL) that claim effectiveness of any intervention for mental disorders. The abstract conclusions will be categorised into three types: superior (only stating significant superiority of intervention to control), limited (suggesting that intervention has limited superiority to control) and equal (claiming equal effectiveness of intervention as control). The full texts will also be classified as one of the following based on the primary outcome results: significant (all primary outcomes were statistically significant in favour of the intervention), mixed (primary outcomes included both significant and non-significant results) or all non-significant results. By comparing the abstract conclusion classification and that of the corresponding full text, we will assess whether each study exhibited overstatements in its abstract conclusion. Ethics and dissemination: This trial requires no ethical approval. We will publish our findings in a peer-reviewed journal. Trial registration number: UMIN000018668; Pre-results

Antidepressants, benzodiazepines and azapirones for panic disorder in adults:a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare individual active drugs (antidepressants, benzodiazepines and azapirones) and placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank treatments for panic disorder (antidepressants, benzodiazepines, azapirones and placebo) according to their effectiveness and acceptability

Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder:a systematic review and network meta-analysis

Background Major depressive disorder is one of the most common, burdensome and costly psychiatric disorders worldwide in adults. Both pharmacological and non-pharmacological treatments are available, however, because of lack of resources, antidepressants are used more frequently. Prescription of these agents should be informed by the best available evidence. Consequently, we aimed to update and expand our previous work to compare and rank antidepressants for major depressive disorder in adults. Methods We searched Cochrane CENTRAL, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to January 8th 2016, for the acute treatment of major depressive disorder diagnosed according to standard operationalised criteria. We included placebo-controlled and head-to-head trials of 21 antidepressants in adults. We assessed the certainty of evidence using GRADE. Primary outcomes were efficacy (response rate) and acceptability (discontinuations due to any cause). Secondary outcomes included symptom severity, remission rate and discontinuations due to adverse events. We estimated summary odds ratios (OR) and standardised mean differences (with 95% credibility intervals - 95% CrIs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO (CRD42012002291). Findings We included 522 trials with 116,477 participants. The certainty of evidence was moderate to very low. In terms of efficacy, all antidepressants were more effective than placebo, with OR ranging between 2·13 (95% CrI 1·89 to 2·41) for amitriptyline and 1·38 (95% CrI 1·16 to 1·63) for reboxetine. For acceptability, agomelatine and fluoxetine were associated with fewer dropouts than placebo (OR 0·84, 95% CrI 0·72 to 0·97 and 0·88, 95% CrI 0·80 to 0·96, respectively), while clomipramine was worse than placebo (OR 1.31, 95% CrI 1·01 to 1·68). When all trials were considered, differences in OR between antidepressants ranged from 1·15 (95% CrI 1·04 to 1·27) to 1·55 (95% CrI 1·27 to 1·91) for efficacy and from 0.64 (95% CrI 0·48 to 0·86) to 0.85 (95% CrI 0·75 to 0·96) for acceptability, with wide confidence intervals on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, sertraline, venlafaxine and vortioxetine were more effective than other antidepressants (OR range: 1.12 [95% CrI 1·00 to 1·32] to 1.96 [95% CrI 1·09 to 3·57]), while fluoxetine, reboxetine and trazodone were the least efficacious drugs (OR range: 0.51 [95% CrI 0·72 to 0·97] to 0.89 [95% CrI 0·72 to 0·97]). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine were the best drugs (OR range: 0.42 [95% CrI 0·72 to 0·97] to 0.81 [95% CrI 0·72 to 0·97]), while amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone and venlafaxine had the highest dropout rates (OR range: 1.23 [95% CrI 1·00 to 1·32] to 2.37 [95% CrI 1·00 to 1·32]). Interpretation All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, while there was more variability in efficacy and rate of drop out in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers and policy-makers on the relative merits of the different antidepressants.</p

Comparing methods for estimating patient-specific treatment effects in individual patient data meta-analysis.

Meta-analysis of individual patient data (IPD) is increasingly used to synthesize data from multiple trials. IPD meta-analysis offers several advantages over meta-analyzing aggregate data, including the capacity to individualize treatment recommendations. Trials usually collect information on many patient characteristics. Some of these covariates may strongly interact with treatment (and thus be associated with treatment effect modification) while others may have little effect. It is currently unclear whether a systematic approach to the selection of treatment-covariate interactions in an IPD meta-analysis can lead to better estimates of patient-specific treatment effects. We aimed to answer this question by comparing in simulations the standard approach to IPD meta-analysis (no variable selection, all treatment-covariate interactions included in the model) with six alternative methods: stepwise regression, and five regression methods that perform shrinkage on treatment-covariate interactions, that is, least absolute shrinkage and selection operator (LASSO), ridge, adaptive LASSO, Bayesian LASSO, and stochastic search variable selection. Exploring a range of scenarios, we found that shrinkage methods performed well for both continuous and dichotomous outcomes, for a variety of settings. In most scenarios, these methods gave lower mean squared error of the patient-specific treatment effect as compared with the standard approach and stepwise regression. We illustrate the application of these methods in two datasets from cardiology and psychiatry. We recommend that future IPD meta-analysis that aim to estimate patient-specific treatment effects using multiple effect modifiers should use shrinkage methods, whereas stepwise regression should be avoided