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Introduction: A consequence of corporate influence on public policy is the potential for negative impacts on population health. Consequently, it is imperative that public health advocates and scholars stay abreast of emerging corporate practices designed to influence regulatory measures aimed at safeguarding health. To identify these emerging practices, we attended a national corporate affairs conference to identify tactics and gain insights from the range of commercial actors presenting at the event. Method: An observational design was used for the research. This involved observation of senior executives presenting at a national corporate affairs conference in Australia in 2023. The collected data was inductively and thematically analyzed by the authors. Results: Our findings revealed that the foremost concern for corporations was maintaining a "social license to operate." Notably, corporate actors perceived social media as a critical threat to social license as it can rapidly sway public opinion against them. Strategies identified for preserving social license included building relationships with the public and civil society, leveraging AI-driven data services to monitor and effectively respond to perceived threats, to convert dissenters into advocates, and applying the narrative of value creation and stakeholder capitalism. Conclusion: This study contributes valuable insights for public health advocates and scholars by shedding light on the mechanisms employed by corporations to counteract regulatory measures. These mechanisms include using stakeholder capitalist narratives to frame and reframe discussion and debate, engaging dissenters to convert them into advocates, and leveraging partnerships to camouflage actions and build social license halos. It also revealed the unprecedented power and new platforms that previously weak actors now have via social media. The observations from the conference offer a nuanced understanding of corporate strategies, enabling advocates to effectively challenge prevailing narratives that may undermine public health initiatives. [ABSTRACT FROM AUTHOR]

Background: Both brain abscess(BA)and glioblastoma (GBM) are common causative pathologies of intraparenchymal ring-enhancing lesions. Advanced MR sequences such as diffusion weighted image (DWI) were often used to increase distinguishability of both entities. Purpose: To evaluate the value of asphericity (ASP) from conventional T1-weighted MR images in differentiating BA from morphologically similar ring-enhancing GBM. Material and Methods: Twenty-one BA and twenty-nine GBM were retrospectively included in this study. Each region of interest (ROI) was delineated twice with the software of ITK-SNAP on the contrast-enhanced T1 images by two observers. ASP was calculated to define the relative deviation of the ROI's shape from a sphere. Intraclass correlation coefficients (ICC) for inter-observer and intra-observer were calculated. The diagnostic capabilities of ASP and conventional volume (VOL) of ROI were evaluated with receiver operating characteristic (ROC) curve analysis. In addition, areas under the ROC curves of ASP and VOL were compared. Results: ICC of intra-observer and inter-observer were 0.99 (95% confidence interval, [CI] 0.97–0.99) and 0.98 (0.95–0.99), respectively. Both ASP and VOL showed significant difference between BA and GBM. The mean ASP values for BA and GBM were 66.3±7.8 and 14.7±1.8, respectively. The mean VOL value of BA was also larger than that of GBM (47.2±7.4 vs. 20.7±1.5 mm3). The mean AUC of ASP and VOL were 0.977 (95% CI 0.944–1) and 0.86 (95% CI 0.746–0.974), respectively. The AUC of ASP was significantly higher than that of VOL (p=0.04). The optimal cut point values of ASP and VOL were 24.39 and 24.86 mm3, respectively. Conclusions: ASP derived from routine MRI is useful in differentiating BA from GBM. [ABSTRACT FROM AUTHOR]

Objectives: Predicting post-hepatectomy liver failure (PHLF) after extended right hepatectomy following portal vein embolization (PVE) from serial gadoxetic acid-enhanced magnetic resonance imaging (MRI).Methods: Thirty-six patients who underwent hepatectomy following PVE were evaluated prospectively with gadoxetic acid-enhanced MRI examinations at predefined intervals during the course of their treatment, i.e., before and 14 days and 28 days after PVE as well as 10 days after hepatectomy. Relative enhancement (RE) and volume of the left and right liver lobes were determined. The study population was divided into two groups with respect to signs of PHLF. Differences between the two groups were assessed using the Mann-Whitney U test, and predictive parameters for group membership were investigated using ROC and logistic regression analysis.Results: RE of the left lobe prior to PVE versus 14 days after PVE was significantly lower in patients with PHLF than in those without PHLF (Mann-Whitney U test p < 0.001) and proved to be the best predictor of PHLF in ROC analysis with an AUC of 0.854 (p < 0.001) and a cutoff value of - 0.044 with 75.0% sensitivity and 92.6% specificity. Consistent with this result, logistic linear regression analysis adjusted for age identified the same parameter to be a significant predictor of PHLF (p = 0.040).Conclusions: Gadoxetic acid-enhanced MRI performed as an imaging-based liver function test before and after PVE can help to predict PHLF. The risk of PHLF can be predicted as early as 14 days after PVE.Key Points: • To predict the likelihood of post-hepatectomy liver failure, it is important to estimate not only future liver remnant volume prior to extended liver resection but also future liver remnant function. • Future liver remnant function can be predicted by performing gadoxetic acid-enhanced MRI as an imaging-based liver function test before and after portal vein embolization. • A reduction of relative enhancement of the liver in gadoxetic acid-enhanced MRI after portal vein embolization of 0.044 predicts post-hepatectomy liver failure with 75.0% sensitivity and 92.6% specificity. [ABSTRACT FROM AUTHOR]

Purpose: To assess in a large naturalistic sample, whether clinical response to a treatment with venlafaxine is associated with different patterns of plasma concentrations of active moiety, AM (sum of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN)). Methods: Applying a regression model, plasma concentrations and plasma concentrations corrected-by-dosage (C/D) for AM were included as independent variable with Clinical Global Impressions-Improvement (CGI-I) scale ratings as dependent variable. Moreover, AM, VEN, and ODVEN were compared between treatment responders and non-responders, defining response as much or very much improved on the CGI-I scale based on the non-parametric Mann-Whitney U (M-W-U) test with a significance level of 0.05. Results: No correlations were found between AM and C/D AM plasma concentrations and CGI-I ratings (regression coefficient 0.0, CI 0.000, 0.001, p = 0.492 for AM and 0.047, CI − 0.065, 0.159, p = 0.408 for C/D AM). Venlafaxine daily dosage did not differ between responders and non-responders (217.7 ± 76.9 vs. 222.0 ± 72.7 mg/day, p = 0.45 for M-W-U). Responders displayed lower ODVEN (p = 0.033) and AM (p = 0.031) plasma concentrations than non-responders (p = 0.033 and 0.031, respectively for M-W-U). No other differences were detected. Using a cut-off level of 400 ng/mL for AM concentrations, a higher percentage of responders was reported in the group of patients with AM < 400 ng/mL (13.04%) compared to patients with AM > 400 ng/mL (8%) (p = 0.038). Conclusions: Higher ODVEN and AM concentrations in non-responders than in responders indicate that treatment escalation above upper thresholds of therapeutic reference ranges of venlafaxine is not promising. Hence, the therapeutic reference range for venlafaxine can help in improving outcomes in a measurement-based care model that takes advantage of therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Despite increasing prescription rates of antidepressants in pregnant and breastfeeding women over the past decades, evidence of drug exposure for neonates through lactation is very sparse. Concentrations of three antidepressants citalopram, sertraline, and venlafaxine were measured in maternal blood and breast milk in 17 women receiving antidepressant therapy during breastfeeding period. We also computed concentration-by-dose-ratios (C/D) and milk to serum (plasma) penetration ratios (M/P). Non-parametric tests were applied. Serum concentration of citalopram and daily dosage correlated positively while daily dosage and mother milk concentration did not (rho = 0.939, p = 0.005, and rho = 0.772, p > 0.05 respectively). A significant correlation was also found between serum and milk concentrations (rho = 0.812, p = 0.05). Venlafaxine daily dosage correlated positively with the active moiety milk concentration (rho = 0.949, p = 0.014). No significant correlations were reported for sertraline. The amount of antidepressant concentrations to which neonates may be exposed, assessed as absolute infant dose (AID), was particularly low with the highest median AID being 0.16 mg/kg/day for venlafaxine. No significant difference was detected for the M/P ratios between different drugs (p > 0.05), whereas the comparison of C/D ratios revealed lower values in the sertraline group, with the highest values reported for citalopram group (p = 0.007 for serum concentrations and p = 0.008 for mother milk). Findings suggest that breastfeeding under antidepressant treatment constantly exposes children with measurable drug concentrations. As daily dosage and serum concentration of the antidepressants did not predict drug concentrations in mother milk, measuring of drug concentrations in milk helps to quantify drug exposure during breastfeeding. More data—even data of drug concentrations in breastfed children—are needed to better assess the effects of drug exposure on children's development. [ABSTRACT FROM AUTHOR]

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Abstract: This work does a systematic comparative evaluation of 2 methods originating from different fields, both dedicated to the problem of curve resolution/unmixing: multivariate curve resolution–alternating least squares (MCR‐ALS) and band‐target entropy minimization (BTEM). The MCR‐ALS factorizes the data matrix into spectral and concentration profiles that satisfy constraints expressing physicochemical knowledge on the analyzed system. The BTEM reconstructs the pure components' spectral profiles as linear combinations of singular vectors that minimize the spectral entropy and contain specific peaks. Both methods were applied to 40 simulated and one real data set. The simulated data were generated from real spectral and concentration profiles that include different types of spectroscopy (mass spectrometry, Raman, and UV‐visible), data structures (random mixtures, images, and reaction system), and noise levels; the real data set was a Raman image of kidney calculus. For most data sets, both methods yielded accurate solutions, with a correlation between reference and resolved profiles >0.99. However, MCR‐ALS (here used with nonnegativity constraint only) was affected by rotational ambiguity in the recovery of spectral profiles coming from systems with high correlation or overlap in the concentration direction, whereas BTEM tended to distort UV‐visible spectra, a kind of measurement far in nature from low entropy conditions. MCR‐ALS solutions were more stable than BTEM to the increase in noise level. This work also explores the possibility of combining the 2 methods by performing them in sequence. The results show that this combination can significantly improve the outcome as compared to either method applied alone. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: An increasing trend in prescribing proton pump inhibitors (PPIs) inevitably increases the risk of unwanted drug-drug interactions (DDIs). The aim of this study was to uncover pharmacokinetic interactions between two PPIs-omeprazole and pantoprazole-and venlafaxine.Methods: A therapeutic drug monitoring database contained plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine. We considered three groups: a group of patients who received venlafaxine without confounding medications (non-PPI group, n = 906); a group of patients who were comedicated with omeprazole (n = 40); and a group of patients comedicated with pantoprazole (n = 40). Plasma concentrations of venlafaxine, O-desmethylvenlafaxine and active moiety (venlafaxine + O-desmethylvenlafaxine), as well as dose-adjusted plasma concentrations, were compared using non-parametrical tests.Results: Daily doses of venlafaxine did not differ between groups (p = 0.949). The Mann-Whitney U test showed significantly higher plasma concentrations of active moiety, as well as venlafaxine and O-desmethylvenlafaxine, in both PPI groups [p = 0.023, p = 0.011, p = 0.026, +29% active moiety, +27% venlafaxine, +36% O-desmethylvenlafaxine (pantoprazole); p = 0.003, p = 0.039 and p < 0.001, +36% active moiety, +27% venlafaxine, +55% O-desmethylvenlafaxine (omeprazole)]. Significantly higher concentration-by-dose (C/D) values for venlafaxine and active moiety were detected in the pantoprazole group (p = 0.013, p = 0.006, respectively), while in the omeprazole group, C/D ratios for all three parameters-venlafaxine, O-desmethylvenlafaxine and active moiety-were significantly higher (p = 0.021, p < 0.001 and p < 0.001, respectively).Conclusions: Significantly higher plasma concentrations for all parameters (venlafaxine, O-desmethylvenlafaxine, active moiety) suggest clinically relevant inhibitory effects of both PPIs, most likely on the cytochrome P450 (CYP) 2C19-mediated metabolism of venlafaxine. The findings might be the result of different degrees of CYP2C19 involvement, therefore the inhibition of CYP2C19 by both PPIs may lead to an increased metabolism via CYP2D6 to O-desmethylvenlafaxine. [ABSTRACT FROM AUTHOR]

Objectives: Off-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals. Methods: In this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject’s mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial. Results: Of the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well. Conclusion: We found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week’s treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk–benefit evaluation in cases of off-label prescription of antipsychotic medications. [ABSTRACT FROM AUTHOR]

Objectives: Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalized treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient subgroups such as children, adolescents, pregnant women, elderly patients, patients with intellectual disabilities, patients with substance use disorders, individuals with pharmacokinetic peculiarities and forensic patients. Clear indications for TDM include lack of clinical response in the therapeutic dose range, assessment of drug adherence, tolerability issues and drug-drug interactions.Methods: Based upon existing literature, recommended therapeutic reference ranges, laboratory alert levels, and levels of recommendation to use TDM for dosage optimization without specific indications, conversion factors, factors for calculation of dose-related drug concentrations and metabolite-to-parent ratios were calculated.Results: This summary of the updated consensus guidelines by the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie offers the practical and theoretical knowledge for the integration of TDM as part of pharmacotherapy with neuropsychiatric agents into clinical routine.Conclusions: The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment. [ABSTRACT FROM AUTHOR]

Background: The objective of this retrospective study was to compare the effectivity and tolerability of diazepam and clomethiazole in the treatment of alcohol withdrawal syndrome (AWS) in a large clinical sample.Methods: The data of 566 patients admitted to an intensive care psychiatric unit in Germany (2010-2014) were evaluated. The course of withdrawal was analyzed on a matched sample (n = 152) consisting of a diazepam group (n = 76) and a clomethiazole group (n = 76). Medical assessment was based on a standardized point-based symptom rating scale called AESB (Alkoholentzugssymptom-Bogen), a German modified version of the Revised Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar).Results: Although the mean daily symptom reduction did not differ significantly, patients treated with clomethiazole were treated significantly shorter and needed less concomitant antipsychotic medication. Numbers of complications and adverse events did not show significant differences.Conclusion: Both clomethiazole and diazepam were effective and equally safe in the treatment of AWS. Clomethiazole provided a faster withdrawal and required less concomitant antipsychotic medication and therefore might be the more favorable option for patients and physicians. Taken into account the methodological limitations of the study (retrospective design, secondary matching, missing randomization, use of clomethiazole as drug of first choice), further studies are needed to confirm this result. [ABSTRACT FROM AUTHOR]

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The purpose of this study was to disentangle an association between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety, AM (RIS + 9-OH-RIS), and clinical response in a naturalistic sample. Plasma concentrations of RIS, 9-OH-RIS and AM in patients out of a therapeutic drug monitoring (TDM) database were compared between responders ( n = 64) and non-responders ( n = 526) using the Clinical Global Impressions (CGI) Scale. Daily dosage of risperidone did not differ between responders and non-responders. Differences for active moiety plasma levels between the two groups did not reach statistical significance. However, responders showed lower plasma concentrations of the parent compound RIS as well as lower metabolic ratios RIS/9-OH-RIS than non-responders ( p = 0.017 and p = 0.034). These differences did not remain after controlling for age and baseline symptoms. Furthermore, the cohort was split into two subgroups based on the daily dosage: patients under high (≥6 mg/day) ( R , n = 187) and patients under lower dosages (<6 mg) ( R , n = 403) of risperidone. Differences between responders and non-responders after controlling for demographic and clinical characteristics remained only for plasma concentrations of active moiety in the lower-dose medicated groups; non-responders showed higher active moiety plasma concentrations than responders. Understanding the mechanisms involved and factors associated with the clinical response in patients medicated with antipsychotics is of great interest. Our data imply that clinical response to an antipsychotic treatment cannot be attributed to a single pharmacokinetic pattern. It seems to be rather a complex patchwork of influencing factors such as demographic and clinical characteristics as well as the metabolizer status as surrogate of CYP activity. It seems that the ratio between RIS and 9-OH-RIS may play a crucial role in mediating the clinical effect. [ABSTRACT FROM AUTHOR]

Background: Safety concerns are increasingly raised regarding the use of gadolinium-based contrast media for MR imaging.Objective: To determine the accuracy of pre-contrast abdominal MR imaging for lesion detection and characterization in pediatric oncology patients.Materials and Methods: We included 120 children (37 boys and 83 girls; mean age 8.94 years) referred by oncology services. Twenty-five had MRI for the first time and 95 were follow-up scans. Two authors independently reviewed pre-contrast MR images to note the following information about the lesions: location, number, solid vs. cystic and likely nature. Pre- and post-contrast imaging reviewed together served as the reference standard.Results: The overall sensitivity was 88% for the first reader and 90% for the second; specificity was 94% and 91%; positive predictive value was 96% and 94%; negative predictive value was 82% and 84%; accuracy of pre-contrast imaging for lesion detection as compared to the reference standard was 90% for both readers. The difference between mean number of lesions detected on pre-contrast imaging and reference standard was not significant for either reader (reader 1, P = 0.072; reader 2, P = 0.071). There was substantial agreement (kappa values of 0.76 and 0.72 for readers 1 and 2) between pre-contrast imaging and reference standard for determining solid vs. cystic lesion and likely nature of the lesion. The addition of post-contrast imaging increased confidence of both readers significantly (P < 0.0001), but the interobserver agreement for the change in confidence was poor (kappa 0.12).Conclusion: Pre-contrast abdominal MR imaging has high accuracy in lesion detection in pediatric oncology patients and shows substantial agreement with the reference standard for characterization of lesions. Gadolinium-based contrast media administration cannot be completely eliminated but can be avoided in many cases, with the decision made on a case-by-case basis, taking into consideration location and type of tumor. [ABSTRACT FROM AUTHOR]

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The article presents abstracts of studies to be discussed at the American College of Neuropsychopharmacology 54th Annual Meeting to be held on December 7, 2015 which include changes in the functional brain connectivity and verbal memory performance, mental healthcare access for state-of-the-art treatments, and study of sex differences in memory decline.

Rationale: Many aspects of the neurobiology of schizophrenia, especially the physiological basis of the negative symptoms and associated cognitive deficits, remain inadequately understood. Tandon and Greden () postulated a central role of dopaminergic/cholinergic imbalance in schizophrenia. Objective/Methods: In light of this hypothesis, we elected to investigate the effects of anticholinergic challenge on psychopathology, cognition and attention in 12 unmedicated patients with schizophrenia and 12 healthy controls. The first examination occurred before any pharmacological intervention; the second examination was carried out immediately following an intravenous infusion of 5 mg biperiden, a centrally acting antimuscarinergic agent. Results: The biperiden challenge provoked a considerable increase in PANSS scores in both groups which was significantly more pronounced in patients (repeated measures analysis of variance (ANOVA) (rmANOVA): F( df) = 6.4(1,22); p = 0.019). The increase in the PANSS scores showed a significant negative correlation with age in patients. Biperiden caused considerable cognitive impairments in both groups. A significant group difference (rmANOVA) could be observed for TMT-B ( F( df) = 11.29(1,22); p = 0.003). Conclusions: The anticholinergic intervention caused more pronounced psychopathological and cognitive deteriorating effects in patients suffering from schizophrenia than in healthy volunteers. This could be related to the disrupted cholinergic transmission in schizophrenia. Our findings speak on behalf of the need of a more restrictive use of anticholinergics in psychiatric patients. The age-related attenuation of PANSS score increases in patients could be related to the age-dependent changes in dopamine dynamics and also to the age-associated decline of the availability of muscarinic receptors. Our results emphasise the need for further investigation of cholinergic disturbances in schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade. Methods: Ninety-five patients with 139 renal masses (93 malignant and 46 benign) who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest) and from the whole tumour (R2*whole). Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis. Results: The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8). The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79) was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2]) and R2*largest (AUC=0.75[observer1]) was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p<0.01 for R2*whole[observer1] vs R2*largest[observer2]) than R2*largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC, both R2*whole and R2*largest were good (all > 0.7) and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1]). Conclusions: BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross-section, assessing the whole tumour provides better inter-observer agreement in parameter measurement for differentiating renal cell carcinoma from benign renal masses. [ABSTRACT FROM AUTHOR]

Rationale: The aim of this study was to investigate the distribution pattern of mirtazapine and its metabolite normirtazapine ( N-desmethylmirtazapine) in blood and cerebrospinal fluid (CSF). Objectives and methods: Concentrations of mirtazapine were measured in blood serum and CSF of 16 patients treated with daily doses of 7.5-60 mg. Daily doses were correlated with serum and CSF concentrations as well as serum levels with those in CSF. Results: Serum levels of mirtazapine and normirtazapine showed a strong relation to the daily dose of mirtazapine of r = +0.631 and r = +0.732, respectively ( p < 0.01). Between the daily doses and the CSF levels of both mirtazapine and normirtazapine, we only found a trend-wise correlation ( r = +0.535, p = 0.060). The correlation between mirtazapine and normirtazapine in serum and CSF was highly significant ( r = +0.664, p = 0.005 and r = +0.885, p < 0.001, respectively). High discrepancies between (total) mirtazapine levels in serum and CSF indicate a low penetration into CSF with regard to the total serum concentration as the mean of the calculated penetration ratio was 0.16 (SD = 0.11). By correcting the penetration ratio for the plasma protein binding, the mean CSF/serum ratio for the unbound fraction was 1.05 (SD 0.72, range 0.56-3.19) indicating a high passage into CSF. Conclusions: Findings indicate a good ability of mirtazapine and normirtazapine to overcome the blood-cerebrospinal fluid barrier and suggest a high ability to enter the brain with sufficient drug levels at the target sites within the brain contributing to clinical efficacy. [ABSTRACT FROM AUTHOR]

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Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses the regulatory support program at a large academic health center and its acquisition of eSub capability for drugs and devices. It describes the steps involved and the challenges and explores the use of expert technical consulting and software solutions. Moreover, it examines the impact of eSubmissions on the regulatory operations metrics, agency interaction and industry interaction.

Although neurotransmitter-based hypotheses still prevail current thinking about the mechanism of action of psychotropic drugs, recent insight into the pathophysiology of psychiatric disorders has unveiled a range of new therapeutic actions of the drugs used to treat those disorders. Especially antidepressants seem to exert at least some of their effects via restoration of synaptic/neuronal plasticity. In addition, there is increasing evidence that several of the second-generation antipsychotics and some anticonvulsants affect neuronal survival/apoptosis as well as synaptic plasticity. Most of this evidence stems from work in animals. In this review, we will focus on the evidence for neuroplastic effects of psychotropic drugs in humans being aware of the fact that most of the data are derived from animals and that volumetric studies in humans can only indicate structural plasticity and not necessarily functional plasticity. However, as the data from human studies are rather poor and inconclusive, and sometimes even conflicting, it seems impossible to draw general conclusions. Until now studies on neuroplasticity in humans can only explain small pieces of the effects of psychotropic drugs on brain plasticity in humans. Nevertheless, future prospects for the development of new drugs targeting brain plasticity will be of importance and will complete this overview. [ABSTRACT FROM AUTHOR]

Cariprazine is a novel drug with partial agonist activity at dopamine D2/3 receptors and six- to eightfold higher affinity for human dopamine D3 over D2 receptors. Results from several placebo-controlled Phase II/III trials in patients with a The Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of schizophrenia or bipolar I disorder suggest that cariprazine is superior to placebo with respect to antipsychotic and antimanic activity. Reports concerning safety and tolerability of cariprazine are mainly favorable, although the rates of treatment-associated adverse events, which most commonly included akathisia and extrapyramidal symptom, are rather high. However, only minor alterations of clinical laboratory values, prolactin concentrations and ECG parameters are reported in cariprazine-treated patients. A new drug application to the U.S. F DA for cariprazine for the treatment of both schizophrenia and manic or mixed episodes associated with bipolar I disorder was submitted in November 2012. A more precise assessment of the clinical properties of this new drug will require additional studies, aimed to compare and contrast cariprazine with other antipsychotic agents. [ABSTRACT FROM AUTHOR]

Background: The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. Methods: This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). Results: The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). Conclusion: The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cognitive impairments can be observed in the majority of diseases with disturbed dopamine transmission. They are considered as core symptoms of schizophrenia, a disorder in which they appear to be particularly pronounced. Their neurobiological background is not yet sufficiently investigated, but dopaminergic systems are believed to play a crucial role. The aim of this single-blind, randomised, placebo-controlled study was to examine the effects of subchronic antidopaminergic treatment on cognitive functions in healthy subjects. In total, 72 healthy volunteers, randomised into four groups, received one antidopaminergic substance (aripiprazole, haloperidol or reserpine) or placebo, respectively, for 7 days. A comprehensive neurocognitive assessment was conducted at baseline, 24 h after the last medication intake and 7 days later. In the Digit Symbol Substitution Test a distinct, statistically significant improvement was measured in the second session in the placebo but not in the medication group. A significant group*time interaction for reaction times in three subtests of the Test battery for Attentional Performance (TAP) was also found. Our findings indicate that modulation of dopaminergic systems affects primarily speed of information processing, attention and learning. Absence of effects on other functions, differing from previous reports, may be an expression of a sufficient counter-regulation. [ABSTRACT FROM AUTHOR]

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Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)