Relationship between psychosocial adjustment and executive function in patients with bipolar disorder and schizophrenia in remission: the mediating and moderating effects of insight

Objectives: The aims of this study were to examine the relationships between executive function and psychosocial adjustment, and the mediating and moderating effects of insight on the association between executive function and psychosocial adjustment in patients with bipolar disorder and schizophrenia in clinical remission. Methods: The level of psychosocial adjustment was assessed in 96 subjects with bipolar disorder and 96 subjects with schizophrenia who were in remitted state. The association between executive function and psychosocial adjustment and the mediating and moderating effects of insight were examined by multiple regression analysis models and the Goodman test. Results: The results indicated that executive function had direct effect on psychosocial adjustment in both subjects with bipolar disorder and schizophrenia. However, the mediating effect of insight on the association between executive function and psychosocial adjustment was only found in subjects with schizophrenia, but not in subjects with bipolar disorder. No moderating effect of insight on the association between executive function and psychosocial adjustment was found in subjects with schizophrenia or bipolar disorder. Conclusions: The results of this study indicated that executive function has an important role in psychosocial adjustment in both patients with bipolar disorder and schizophrenia. Meanwhile, insight has a different role in the association between executive function and psychosocial adjustment between patients with bipolar disorder and schizophrenia.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Biomechanical evaluation of segmental instability in degenerative lumbar spondylolisthesis

Here we investigated the biomechanical properties of spinal segments in patients with degenerative lumbar spondylolisthesis (DLS) using a novel intraoperative measurement system. The measurement system comprised spinous process holders, a motion generator, a load cell, an optical displacement transducer, and a computer. Cyclic displacement of the holders produced flexion-extension of the segment with all ligamentous structures intact. Stiffness, absorption energy (AE), and neutral zone (NZ) were determined from the load-deformation data. Forty-one patients with DLS (M/F = 15/26, mean age 68.6 years; Group D) were studied. Adjacent segments with normal discs in six patients (M/F = 3/3, mean age 35 years) were included as a control group (Group N). Flexion stiffness was significantly lower in Group D than in Group N. The NZ, however, was significantly greater in Group D than in Group N. Thus, compared to normal segments, spinal segments with DLS had a lower flexion stiffness and a higher NZ. NZs in Group D were, however, widely distributed compared to those in Group N that showed NZ <2 mm/N in all cases, suggesting that the segment with DLS is not always unstable and that the segments with NZ >2 mm/N can be considered as unstable. A patent application for the intraoperative measurement system has been submitted.     

Effects of Ketoconazole on the Pharmacokinetic Properties of CG100649, A Novel NSAID: A Randomized,Open-Label Crossover Study in Healthy Korean Male Volunteers

Background

CG100649, a novel selective cyclooxygenase-2 inhibitor that also inhibits carbonic anhydrase I/II, is expected to reduce the cardiovascular risk typical of other NSAIDs. Concurrent medications may influence the activities of the cytochrome P450 (CYP) 3A enzyme through which CG100649 is metabolized.

Objectives

This study was designed to evaluate the influence of ketoconazole, a known strong inhibitor of CYP3A, on the pharmacokinetic properties of CG100649.

Methods

This randomized, open-label, 2 × 2 crossover study was conducted in healthy Korean male volunteers. Each subject received the following 2 treatments in a randomly allocated sequence, separated by a washout period of 42 days: single oral dose of CG100649 6 mg, and concurrent dosing of CG100649 6 mg and ketoconazole 400 mg followed by ketoconazole 400 mg/d over 4 days. Blood samples for pharmacokinetic analysis were collected at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 240, 384, and 480 hours after dosing of CG100649 in each sequence. Tolerability assessments were performed throughout the study.

Results

Thirty subjects participated, and 26 subjects completed the study. Seventeen adverse events (AEs) were reported in 10 subjects, and all AEs were recovered without any sequelae. No serious AEs were reported. Six subjects receiving the single dose of CG100649 had 9 AEs, and 7 subjects receiving the combination of ketoconazole and CG100649 had 8 AEs. The C_max of CG100649 with CG100649 only and with concurrent administration of CG100649 + ketoconazole were similar (10.7 and 11.0 ng/mL, respectively). The CG100649 AUC_last with concurrent ketoconazole was 1.29-fold greater than that with CG100649 only (2074.0 and 2685.8 ng · h/mL) and demonstrated a statistically significant difference (P < 0.05). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or AEs between treatments.

Conclusion

Although the AUC of CG100649 increased by 29% with the concurrent medication of ketoconazole, it is considered that concurrent administration of CG100649 with ketoconazole would not change the safety profile of CG100649. ClinicalTrials.gov identifier: NCT01154764.     

Outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients

Purpose

The outcomes and predictors of mortality from Pneumocystis pneumonia (PCP) in HIV-negative patients requiring mechanical ventilation (MV) for respiratory failure were evaluated.

Materials and Methods

This retrospective observational study enrolled 48 patients with PCP requiring MV in the medical intensive care unit (ICU). Multiple logistic regression analysis was used to identify independent predictors of in-hospital mortality.

Results

The main conditions underlying the PCP were malignancies (60%) or post solid organ transplant (35%). Excluding four patients whose initial treatment was changed due to adverse reactions, 21 (44%) of 44 patients did not respond to the initial treatment. During the ICU stay, additional complications developed: shock in 22 (46%), ventilator-associated pneumonia in 16 (33%), and acute kidney injury in 15 (31%). Ultimately, 31 (65%) patients died while hospitalised. In multivariate analysis, hospital mortality was independently associated with severity of illness on ICU admission, failure of initial antimicrobial treatment for PCP, and newly developed shock during ICU stay.

Conclusions

PCP in HIV-negative patients requiring MV for respiratory failure remains a serious illness with high mortality. Failure of the initial antimicrobial treatment for PCP as well as severity of illness was independent predictors of poor outcomes.     

Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support

Introduction

Extracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission.

Methods

Fifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6–20, Area 6–40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated.

Results

Patients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment.

Conclusions

MSsE provides additional prognostic information in patients receiving ECLS.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0548-3) contains supplementary material, which is available to authorized users.     

Direct comparison of stress- and rest-dual-energy computed tomography for detection of myocardial perfusion defect

We assessed the diagnostic performance of stress- and rest-dual-energy computed tomography (DECT) and their incremental value when used with coronary CT angiography (CCTA) compared with combined invasive coronary angiography (ICA)/cardiovascular magnetic resonance (CMR) for detecting hemodynamically significant stenosis causing a myocardial perfusion defect. Forty patients (30 men; mean age, 63.4 ± 8.8 years) with known or suspected coronary artery disease detected by CCTA underwent stress- and rest-DECT, CMR, and ICA. DECT iodine maps were compared with CMR on a per-segment and per-vessel basis. Diagnostic value of CCTA was assessed on a per-vessel basis before and after stress- and rest-DECT and compared to that of ICA/CMR. Compared to CMR, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of rest-DECT for detecting segment (vessel)-based perfusion defects were 29 % (46 %), 88 % (79 %), 56 % (61 %), and 70 % (67 %), respectively. Corresponding values using stress-DECT were 73 % (94 %), 83 % (74 %), 70 % (72 %), and 85 % (95 %), respectively. There was fair (κ = 0.39) agreement between rest- and stress-DECT iodine maps in identifying segments with perfusion defects. Compared with the ICA/CMR for identifying hemodynamically significant stenoses, per-vessel territory sensitivity, specificity, PPV, and NPV of CCTA were 91, 56, 55, and 91 %, respectively; those using CCTA/rest-DECT were 42, 83, 59, and 70 %, respectively; and those using CCTA/stress-DECT were 87, 79, 71, and 91 %, respectively. The area under the receiver operating characteristic curve decreased from 0.74 to 0.62 (P = 0.06) using CCTA/rest-DECT but increased to 0.83 (P = 0.02) using CCTA/stress-DECT. Stress-DECT has incremental value when used with CCTA for detecting hemodynamically significant stenoses.     

Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: an isobolographic analysis

This study was aimed at determining the analgesic effect of gabapentin and tiagabine, two antiepileptic drugs that were administered alone and in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice.Linear regression analysis was used to evaluate the dose-response relationships between logarithms of antiepileptic drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, we calculated doses that increased the antinociceptive effect by 50% (ED₅₀ values) for gabapentin, tiagabine and their combination. The type of interaction between gabapentin and tiagabine was assessed using the isobolographic analysis.Results indicated that both antiepileptic drugs produced the definite antinociceptive effect, and the experimentally derived ED₅₀ values for gabapentin and tiagabine, when applied alone, were 504.4 mg/kg and 5.67 mg/kg, respectively.With isobolography, the experimentally derived ED_{50 mix} value for the fixed ratio combination of 1:1 was 139.31 mg/kg and significantly differed from the theoretically calculated ED_{50 add} value, which was 255.04 mg/kg (p < 0.05), indicating the synergistic interaction between gabapentin and tiagabine in the hot-plate test in mice.In conclusion, the combination of tiagabine with gabapentin at a fixed ratio of 1:1 exerted a synergistic interaction in the mouse model of nociceptive pain. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial for pain relief in humans.