Antipsychotic drug-induced neutropenia: results from the AMSP drug surveillance program between 1993 and 2016.

Neutropenia and agranulocytosis (N&A) are relatively rare, but potentially fatal adverse drug reactions (ADR). This study presents cases of N&A related to one or more antipsychotic drugs (APDs) in psychiatric inpatients. Data on APD utilization and reports of N&A caused by APDs were analyzed by using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2016. 333,175 psychiatric inpatients were treated with APDs for schizophrenia and other indications during the observation period. A total of 124 cases of APD-induced N&A were documented, 48 of which fulfilled the criteria for agranulocytosis, corresponding to a rate of 0.37, respectively, 0.14 in 1000 inpatients treated with APDs. Neutropenia was more often detected in women, whereas there was no difference regarding sex in cases of agranulocytosis. Clozapine had the highest relative risk for inducing N&A and was imputed alone as a probable cause of N&A in 60 cases (1.57‰ of all patients exposed). Perazine showed the second highest relative risk with 8 cases and an incidence 0.52‰, followed by quetiapine (15 cases resp. 0.23‰ of all patients exposed) and olanzapine (7 cases; 0.13‰ of all patients exposed). N&A most often occurred during the first 3 months of treatment. Overall N&A are severe and potentially fatal complications that can occur during treatment with APDs. The results from this study largely agree with the currently available literature, highlighting the positive effects of alertness and established appropriate monitoring.

Acute Enterovirus Encephalitis as a Cause for Isolated Visual and Auditory Hallucinations in a 22-Year-Old Patient.

Viral encephalitis often presents with severe illness, headache, fever, behavioral changes, altered level of consciousness, and focal neurologic deficits. One of the most feared kind of virus encephalitis is herpes simplex encephalitis; however, other central virus infections are also capable of presenting with psychiatric symptoms. Here, we report the case of a 22-year-old woman with first time visual and auditory hallucinations due to an acute enterovirus encephalitis with no cerebrospinal fluid abnormalities but a positive PCR result for enterovirus (ECHO). During treatment, the symptoms deteriorated, and she hat to be shifted to the sheltered ward because of imperative suicidal auditory hallucinations. Under treatment with risperidone and olanzapine, symptoms suddenly stopped and did not reoccur under subsequent reduction of the antipsychotic medication.

Galactorrhea during antipsychotic treatment: results from AMSP, a drug surveillance program, between 1993 and 2015.

Galactorrhea is a well-known adverse drug reaction (ADR) of numerous antipsychotic drugs (APD) and is often distressing for those affected. Methodological problems in the existing literature make it difficult to determine the prevalence of symptomatic hyperprolactinemia in persons treated with APDs. Consequently, a large sample of patients exposed to APDs is needed for more extensive evaluation. Data on APD utilization and reports of galactorrhea caused by APDs were analyzed using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2015. 320,383 patients (175,884 female inpatients) under surveillance were treated with APDs for schizophrenia and other indications. A total of 170 events of galactorrhea caused by APDs were identified (0.97 cases in 1000 female inpatient admissions). Most cases occurred during the reproductive age with the highest incidence among patients between 16 and 30 years (3.81 cases in 1000 inpatients). The APDs that were most frequently imputed alone for inducing galactorrhea were risperidone (52 cases and 0.19% of all exposed inpatients), amisulpride (30 resp. 0.48%), and olanzapine (13 resp. 0.05%). In three cases, quetiapine had a prominent role as a probable cause for galactorrhea. High dosages of the imputed APDs correlated with higher rates of galactorrhea. Galactorrhea is a severe and underestimated condition in psychopharmacology. While some APDs are more likely to cause galactorrhea, we identified a few unusual cases. This highlights the importance of alertness in clinical practice and of taking a patient's individual situation into consideration.

Behavioural change in Prader-Willi syndrome during COVID-19 pandemic.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disorder that in many cases is associated with mental health disorders, in addition to characteristic symptoms such as hyperphagia. The current Sars-CoV-2 coronavirus pandemic has led to massive restrictions in health care and social life worldwide. People with PWS represent a particularly vulnerable population group to these restrictions, with unknown impact on their mental health. METHODS: We conducted an online questionnaire to assess the impact of the restrictions associated with the COVID-19 pandemic on the mental health of people with PWS. RESULTS: One hundred and eight caregivers completed the survey about individuals with PWS. Individuals with PWS > 6 years (n = 89) were included for evaluation with regard to psychopathological change. Respondents frequently reported an increase in psychopathological symptoms associated with PWS during the lockdown, with 51.7% reporting increased temper outbursts, 43.8% showing signs of sadness, 38.2% being anxious, 55.0% more irritable, and 39.3% showing more food seeking behaviour. Adjusted for the type of accommodation food seeking behaviour and irritability is increased to a significantly lesser extent in people with PWS accommodated in specialised care facilities compared with those living in their family home. No significant difference could be found between the sexes. CONCLUSION: The COVID-19 pandemic has had a significant effect on the mental health of individuals with PWS, evidenced by an increase in behaviours associated with PWS, including temper outbursts, food-seeking, and irritability, which again underlines their need for specialised care. Individuals living with their families were particularly vulnerable, indicating that they and their families are in special need of support.

[Psychopharmacotherapy during the COVID-19 pandemic]. / Psychopharmakotherapie in Zeiten der COVID-19-Pandemie.

In view of the current coronavirus disease 2019 (COVID-19) pandemic, patient care, including that of psychiatric patients, is facing unprecedented challenges. Treatment strategies for mental illness include psychotherapy and psychopharmacological interventions. The latter are associated with a multitude of adverse drug reactions (ADR); however, they may currently represent the preferred treatment due to restrictions regarding patient care (i.e. social distancing). Direct contact to patients may have to be reduced in favor of telephone calls or video conferences, so that new techniques in diagnosing and treating patients have to be established to guarantee patient safety. Patients should be extensively informed about relevant ADRs and physicians should actively ask patients about the timely recognition of ADRs. The use of psychotropic drugs may lead to an increased risk of developing ADRs, which are considered to be particularly unfavorable if they occur simultaneously with an acute infection or may even lead to an increased risk of infection. These include respiratory depression, agranulocytosis, intoxication by inhibition of metabolizing enzymes and venous thromboembolism, each of which may be associated with potentially fatal consequences; however, physicians should simultaneously ensure adequate efficacy of treatment, since the ongoing crisis may lead to a worsening of preexisting mental illnesses and to a surge in first onset of psychiatric disorders.

Implementation of a multilevel, multicomponent intervention for obesity control in Native American communities (OPREVENT2): challenges and lessons learned.

OPREVENT2 was a multilevel, multicomponent (MLMC) adult obesity prevention that sought to improve access and demand for healthier food and physical activity opportunities in six Native American communities in the Southwest and Midwest. OPREVENT2 worked with worksites, food stores, schools (grades 2-6), through social media and mailings, and with a local community action committee (CAC), in each of the three intervention communities, and was implemented in six phases. We conducted a process evaluation to assess implementation of each intervention component in terms of reach, dose delivered and fidelity. Implementation of each component was classified as high, medium or low according to set standards, and reported back at the end of each phase, allowing for improvements. The school and worksite components were implemented with high reach, dose delivered and fidelity, with improvement over time. The school program had only moderate reach and dose delivered, as did the social media component. The CAC achieved high reach and dose delivered. Overall, study reach and dose delivered reached a high implementation level, whereas fidelity was medium. Great challenges exist in the consistent implementation of MLMC interventions. The detailed process evaluation of the OPREVENT2 trial allowed us to carefully assess the relative strengths and limitations of each intervention component.

Pharmacotherapeutic management of acute alcohol withdrawal syndrome in critically Ill patients.

INTRODUCTION: Alcohol withdrawal syndrome is a common and life-threatening condition in patients suffering from alcohol use disorder. Treatment of this syndrome is challenging, especially in patients that are critically ill, either because of withdrawal symptoms or underlying conditions. For the treatment, several pharmacological agents exist, such as benzodiazepines, barbiturates, or dexmedetomidine. Nonetheless, as alcohol withdrawal syndromes can occur in every clinical setting, it is necessary to provide a guideline for clinicians confronted with this syndrome in varying clinical contexts. AREAS COVERED: The authors provide a systematic review of the literature found in PubMed and Embase following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. EXPERT OPINION: For the treatment of alcohol withdrawal syndrome, medications targeting the GABA system are preferred. Benzodiazepines are regarded as the gold standard. However, as many adjunct therapeutic options exist, it is essential to find symptom-triggered approaches and treatment protocols for the variety of clinical contexts. Apart from that, it is necessary to compare protocols toward clinical variables rather than investigating medications that are in use for the treatment of alcohol withdrawal syndrome.

A systematic review of strategies to reduce sugar-sweetened beverage consumption among 0-year to 5-year olds.

OBJECTIVE: The objective of this study is to summarize evidence for strategies designed to reduce sugar-sweetened beverage (SSB) consumption among children aged 0 to 5 years. DATA SOURCES: PubMed, Web of Science, EMBASE, CINAHL, ERIC, Cab Abstracts and the Cochrane Central Register of Controlled Trials are the electronic databases searched in this systematic review. STUDY SELECTION: Each included study evaluated an intervention to reduce SSB consumption in children aged 0 to 5 years, was conducted in a high-income country and was published between 1 January 2000 and 15 December 2017. DATA SYNTHESIS: Twenty-seven studies met the inclusion criteria. The primary intervention settings were healthcare (n = 11), preschool/daycare (n = 4), home (n = 3), community venues (n = 3) and other settings (n = 6). Overarching strategies which successfully reduced SSB consumption included (i) in-person individual education, (ii) in-person group education, (iii) passive education (e.g. pamphlets), (iv) use of technology, (v) training for childcare/healthcare providers and (vi) changes to the physical access of beverages. Studies were of moderate methodological quality (average score of 20.7/29.0 for randomized studies; 3.1/9.0 for non-randomized studies). CONCLUSIONS: Evidence suggests that interventions successful at reducing SSB consumption among 0-year to 5-year olds often focused on vulnerable populations, were conducted in preschool/daycare settings, specifically targeted only SSBs or only oral hygiene, included multiple intervention strategies and had higher intervention intensity/contact time.

Leptin Expression and Gene Methylation Patterns in Alcohol-Dependent Patients with Ethyltoxic Cirrhosis-Normalization After Liver Transplantation and Implications for Future Research.

AIMS: Liver transplantation is the only curative treatment available for patients with end-stage alcoholic liver disease. As different studies showed a significant association between leptin plasma levels, gene methylation patterns and the extent of craving in alcohol-dependent patients, we investigated the effect of liver transplantation on leptin expression and promoter methylation. SHORT SUMMARY: The present study shows that in alcohol-dependent patients with liver cirrhosis leptin is significantly higher before liver transplantation and decreases significantly after transplantation. Alcohol-dependent patients on the waiting list had significantly higher leptin promoter methylation values than patients who underwent liver transplantation for other reasons than alcoholic liver disease. METHODS: Only plasma of 118 and peripheral blood mononuclear cells of 121 patients were used: healthy controls (C, n = 24/22), alcohol-dependent patients without ethyltoxic liver cirrhosis (AD, n = 24/22), patients after liver transplantation for other reasons than ethyltoxic liver cirrhosis (C-Tx, n = 18/21), alcohol-dependent patients suffering from ethyltoxic liver cirrhosis on the transplantation waiting list (Pre-Tx, n = 30/28) and patients with prior ethyltoxic liver cirrhosis after liver transplantation (Post-Tx, n = 22/28). RESULTS: Leptin protein was significantly elevated in the pre-transplantation cohort when compared to post-transplantation and alcohol-dependent cohorts. Furthermore, leptin promoter methylation was higher in ethyltoxic patients before transplantation compared to non-ethyltoxic patients after transplantation, but not when compared to ethyltoxic patients after transplantation. C-Tx had lower methylation values than all other groups except for Post-Tx. CONCLUSIONS: Our study outlines the role of leptin protein levels as a marker for AD-related liver damage, contrasting it from AD without severe liver damage. With regard to the results of the methylation analysis, inflammation of the liver appears to cause mechanisms of leptin regulation to deviate from transcriptional regulation. Our data also suggest that leptin regulation is altered in ethyltoxic liver disease when compared to liver cirrhosis caused by other pathologies.

Health Professionals' perceptions of insurance coverage for weight loss services.

Objective: To examine health professionals' (HPs) perceptions of top challenges and solutions in obesity care, and whether these perceptions differ by patient-panel income level. Methods: A 2014 national cross-sectional survey of HPs in nutrition, nursing, behavioural or mental health, exercise and pharmacy was analysed. The dependent variables were identification of insurance coverage for their services as a top (1) challenge or (2) solution for obesity care. The independent variable was self-reported income distribution of HPs' patient panels, which was dichotomized as 'lower-income' if 'mostly low income' or 'higher-income' if 'mostly not low income/evenly split between low-income and not low-income'. Multivariate logistic regression with survey weights was used. Results: Among 450 HPs, mean age was 44.9 years; 86% were women; 44% had lower-income panels. Overall, 25% of HPs endorsed insurance coverage as a current challenge, and 58% viewed improved coverage as a solution. HPs with lower and higher-income patient panels were similarly likely to identify coverage as a challenge (28% vs. 20%, p = 0.33) and benefits expansion as a solution (47% vs. 64%, p = 0.08). Conclusions: Most HPs perceive insurance coverage for their services to benefit patient weight loss. While the Affordable Care Act expands obesity counselling coverage to many lower-income patients, legislation increasing access to benefits for all patients regardless of insurance type may be beneficial.

A systematic review of commercial weight loss programmes' effect on glycemic outcomes among overweight and obese adults with and without type 2 diabetes mellitus.

OBJECTIVE: We examined the glycemic benefits of commercial weight loss programmes as compared with control/education or counselling among overweight and obese adults with and without type 2 diabetes mellitus (T2DM). METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and references cited by individual programmes. We included randomized controlled trials of ≥12 weeks duration. Two reviewers extracted information on study design, population characteristics, interventions, and mean changes in haemoglobin A1c and glucose. RESULTS: We included 18 randomized controlled trials. Few trials occurred among individuals with T2DM. In this population, Jenny Craig reduced A1c at least 0.4% more than counselling at 12 months, Nutrisystem significantly reduced A1c 0.3% more than counselling at 6 months, and OPTIFAST reduced A1c 0.3% more than counselling at 6 months. Among individuals without T2DM, few studies evaluated glycemic outcomes, and when reported, most did not show substantial reductions. DISCUSSION: Few trials have examined whether commercial weight loss programmes result in glycemic benefits for their participants, particularly among overweight and obese individuals without T2DM. Jenny Craig, Nutrisystem and OPTIFAST show promising glycemic lowering benefits for patients with T2DM, although additional studies are needed to confirm these conclusions. © 2016 World Obesity.

Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype.

The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects - mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed.

What childhood obesity prevention programmes work? A systematic review and meta-analysis.

Previous reviews of childhood obesity prevention have focused largely on schools and findings have been inconsistent. Funded by the US Agency for Healthcare Research and Quality (AHRQ) and the National Institutes of Health, we systematically evaluated the effectiveness of childhood obesity prevention programmes conducted in high-income countries and implemented in various settings. We searched MEDLINE®, Embase, PsycINFO, CINAHL®, ClinicalTrials.gov and the Cochrane Library from inception through 22 April 2013 for relevant studies, including randomized controlled trials, quasi-experimental studies and natural experiments, targeting diet, physical activity or both, and conducted in children aged 2-18 in high-income countries. Two reviewers independently abstracted the data. The strength of evidence (SOE) supporting interventions was graded for each study setting (e.g. home, school). Meta-analyses were performed on studies judged sufficiently similar and appropriate to pool using random effect models. This paper reported our findings on various adiposity-related outcomes. We identified 147 articles (139 intervention studies) of which 115 studies were primarily school based, although other settings could have been involved. Most were conducted in the United States and within the past decade. SOE was high for physical activity-only interventions delivered in schools with home involvement or combined diet-physical activity interventions delivered in schools with both home and community components. SOE was moderate for school-based interventions targeting either diet or physical activity, combined interventions delivered in schools with home or community components or combined interventions delivered in the community with a school component. SOE was low for combined interventions in childcare or home settings. Evidence was insufficient for other interventions. In conclusion, at least moderately strong evidence supports the effectiveness of school-based interventions for preventing childhood obesity. More research is needed to evaluate programmes in other settings or of other design types, especially environmental, policy and consumer health informatics-oriented interventions.

[The new reimbursement for psychiatry and psychosomatics - challenges, opportunities and risks of the new financing system]. / Das neue Entgeltsystem für Psychiatrie und Psychosomatik - Herausforderungen, Chancen und Risiken einer neuen Leistungsvergütung.

With the implementation of §â€Š17 d KHG which provides for the introduction of a new, much more performance-based and transparent reimbursement system for psychiatric and psychosomatic hospitals, the Federal Ministry of Health sends the psychiatric and psychosomatic facilities in Germany into a previously unexplored area. Since 2013, there is the possibility of voluntary participation in the new system. Valid from 2015, every other institution will have to deal with the new challenges, opportunities and risks coming along with the structural changes, even though this fact will not have any impact on the individual hospital revenue budget until the end of 2016. There is still some time left to get used to the new system. This paper summarises the key data on the new reimbursement system and explains its content as well as how it works. In addition to that this paper goes into the classification system and clarifies what is essential for a solid preparation. Finally, it comments on the most common criticisms emerging since 2009. How the new system will develop remains to be seen. The fact that it will evolve seems to be certain in terms of a "learning system". It is up to all parties to promote the learning process so as to make effective use of existing potential and keep risks to a minimum.

Maladaptive connectivity of Broca's area in schizophrenia during audiovisual speech perception: an fMRI study.

Speech comprehension relies on auditory as well as visual information, and is enhanced in healthy subjects, when audiovisual (AV) information is present. Patients with schizophrenia have been reported to have problems regarding this AV integration process, but little is known about which underlying neural processes are altered. Functional magnetic resonance imaging was performed in 15 schizophrenia patients (SP) and 15 healthy controls (HC) to study functional connectivity of Broca's area by means of a beta series correlation method during perception of audiovisually presented bisyllabic German nouns, in which audio and video either matched or did not match. Broca's area of SP showed stronger connectivity with supplementary motor cortex for incongruent trials whereas HC connectivity was stronger for congruent trials. The right posterior superior temporal sulcus (RpSTS) area showed differences in connectivity for congruent and incongruent trials in HC in contrast to SP where the connectivity was similar for both conditions. These smaller differences in connectivity in SP suggest a less adaptive processing of audiovisually congruent and incongruent speech. The findings imply that AV integration problems in schizophrenia are associated with maladaptive connectivity of Broca's and RpSTS area in particular when confronted with incongruent stimuli. Results are discussed in light of recent AV speech perception models.

[Nature meets nurture: the importance of epigenetics for the aetiology of psychiatric diseases]. / Nature meets Nurture: Die Bedeutung der Epigenetik für die Ätiologie psychischer Erkrankungen.

A successful therapy requires an understanding and investigation of the aetiology of a disease. Psychiatric diseases represent a special challenge, because environmental factors may play a crucial role in their development as well as possible physiological and genetic causes. Therefore, epigenetics has established itself to be a branch of research that studies the effect of environmental factors on the development of psychiatric diseases, leading to promising new approaches for diagnosis and therapy.

Inside a synesthete's head: a functional connectivity analysis with grapheme-color synesthetes.

Grapheme-color synesthesia is a condition in which letters are perceived with an additional color dimension. To identify brain regions involved in this type of synesthesia and to analyze functional connectivity of these areas, 18 grapheme-color synesthetes and 18 matched controls were stimulated with letters and pseudo-letters presented in black and color in an event-related fMRI experiment. Based on the activation-differences between synesthetes and non-synesthetic controls regions of interest were defined. In a second analysis step functional connectivity was calculated using beta series correlation analysis for these seed regions. First we identified one seed region in the left inferior parietal (IPL) cortex (BA7) showing activation differences between grapheme-color synesthetes and controls. Furthermore, we found activation differences in brain areas involved in processing of letters and pseudo-letters, in particular the right IPL cortex (BA7), but also two more clusters in the right hemispheric BA 18 and BA 40. Functional connectivity analysis revealed an increased connectivity between the left IPL seed region and primary/secondary visual areas (BA 18) in synesthetes. Also the right BA 7 showed a stronger connectivity with primary/secondary visual areas (BA 18) in grapheme-color synesthetes. The results of this study support the idea that the parietal lobe plays an important role in synesthetic experience. The data suggest furthermore that the information flow in grapheme-color synesthetes was already modulated at the level of the primary visual cortex which is different than previously thought. Therefore, the current models of grapheme-color synesthesia have to be refined as the unusual communication flow in synesthetes is not restricted to V4, fusiform cortex and the parietal lobe but rather involves a more extended network.