[How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation]. / Wie die Umsetzung einer Schule für Menschen mit Parkinson-Krankheit gelingen kann ­ Ergebnisse eines Konsensusverfahrens und einer formativen Evaluation.

BACKGROUND: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making. MATERIAL AND METHODS: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis. RESULTS: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents. DISCUSSION: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers.

Telemedical care and quality of life in patients with schizophrenia and bipolar disorder: results of a randomized controlled trial.

BACKGROUND: Schizophrenia and bipolar disorder are serious psychiatric disorders with a high disease burden, a high number of years of life lived with disability and a high risk for relapses and re-hospitalizations. Besides, both diseases are often accompanied with a reduced quality of life (QoL). A low level of quality of life is one predictor for relapses. This study examines whether a telemedical care program can improve QoL. METHODS: Post stationary telemedical care of patients with severe psychiatric disorders" (Tecla) is a prospective controlled randomized intervention trial to implement and evaluate a telemedical care concept for patients with schizophrenia and bipolar disorder. Participants were randomized to an intervention or a control group. The intervention group received telemedical care including regular, individualized telephone calls and SMS-messages. QoL was measured with the German version of the WHOQOL-BREF. Effects of telemedicine on QoL after 6 months and treatment*time interactions were calculated using linear regressions (GLM and linear mixed models). RESULTS: One hundred eighteen participants were recruited, thereof 57.6% men (n = 68). Participants were on average 43 years old (SD 13). The treatment*time interaction was not significant. Hence, treatment had no significant effect either. Instead, gender is an influencing factor. Further analysis showed that social support, the GAF-level and QoL-values at baselines were significant determinants for the improvement of QoL. CONCLUSION: The telemedicine care concept Tecla was not significant for QoL in patients with severe psychiatric disorders. More important for the QoL is the general social support and the level of global functioning of the patients. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00008548, registered 21 May 2015 - retrospectively registered, https://www.drks.de/drks_web/setLocale_EN.do.

Bidimensional structure and measurement equivalence of the Patient Health Questionnaire-9: sex-sensitive assessment of depressive symptoms in three representative German cohort studies.

BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) has been proposed as a reliable and valid screening instrument for depressive symptoms with one latent factor. However, studies explicitly testing alternative model structures found support for a two-dimensional structure reflecting a somatic and a cognitive-affective dimension. We investigated the bidimensional structure of the PHQ-9, with a somatic (sleeping problems, fatigability, appetitive problems, and psychomotor retardation) and a cognitive-affective dimension (lack of interest, depressed mood, negative feelings about self, concentration problems, and suicidal ideation), and tested for sex- and regional-differences. METHODS: We have included data from the GEnder-Sensitive Analyses of mental health trajectories and implications for prevention: A multi-cohort consortium (GESA). Privacy-preserving analyses to provide information on the overall population and cohort-specific information and analyses of variance to compare depressive, somatic and cognitive-affective symptoms between sexes and cohorts were executed in DataSHIELD. In order to determine the dimensionality and measurement invariance of the PHQ-9 we tested three models (1 factor, 2 correlated factors, and bifactor) via confirmatory analyses and performed multi-group confirmatory factor analysis. RESULTS: Differences between sex and cohorts exist for PHQ-9 and for both of its dimensions. Women reported depressive symptoms in general as well as somatic and cognitive-affective symptoms more frequently. For all tested models an acceptable to excellent fit was found, consistently indicating a better model fit for the two-factor and bifactor model. Scalar measurement invariance was established between women and men, the three cohorts, and their interaction. CONCLUSIONS: The two facets of depression should be taken into account when using PHQ-9, while data also render support to a general factor. Somatic and cognitive-affective symptoms assessed by the PHQ-9 can be considered equivalent across women and men and between different German populations from different regions.

Predictors of medication adherence among patients with severe psychiatric disorders: findings from the baseline assessment of a randomized controlled trial (Tecla).

BACKGROUND: Schizophrenia and bipolar disorder are characterized by a high disease burden. Antipsychotic medication is an essential part of the treatment. However, non-adherence is a major problem. Our aim was to examine potential determinants of non-adherence for patients with severe mental disorders. METHODS: Baseline data of the study "Post stationary telemedical care of patients with severe psychiatric disorders" (Tecla) were used. Medication adherence was assessed with the Medication Adherence Report Scale German version (MARS-D). A logistic regression was calculated with age, sex, education, employment status, level of global functioning, social support and intake of typical and atypical antipsychotics as predictors. RESULTS: N = 127 participants were included in the analysis (n = 73 men, mean age 42 years). The mean MARS-D Score was 23.4 (SD 2.5). The most common reason for non-adherence was forgetting to take the medicine. Significant positive determinants for adherence were older age (OR 1.02, 95% CI 1.011-1.024, p < 0.0001), being employed (OR 2.46, 95% CI 1.893-3.206, p < 0.0001), higher level of global functioning (overall measure of how patients are doing) (OR 1.02, 95% CI 1.012-1.028, p < 0.0001), having social support (OR 1.02, 95% CI 1.013-1.026, p < 0.0001), and intake of typical antipsychotics (OR 2.389, 95% CI 1.796-3.178, p < 0.0001). A negative determinant was (female) sex (OR 0.73, 95% CI 0.625-0.859, p = 0.0001). CONCLUSIONS: Especially employment, functioning and social support could be promising targets to facilitate adherence in patients with schizophrenia or bipolar disorder. TRIAL REGISTRATION: This study is retrospectively registered at the German Clinical Trials Register with the trial registration number DRKS00008548 at 21/05/2015.

Molecular-Sensory Decoding of the Citrus latifolia Aroma.

A modified aroma extract dilution approach (AEDA), followed by the determination of flavor dilution (FD) factors, a quantitative analysis and calculation of the relative flavor activity (RFA) and odor activity values (OAVs) as well as recombination experiments were conducted to evaluate the odor- and taste-relevant components of cold-pressed Citrus latifolia peel oil. A 2-fold concentration by distillation and reanalysis, compared with the original oil, revealed relevant components. Partition of the odor-active substances into four reconstitution groups according to their respective FD factors, followed by a recombination, allowed for a better understanding of the contribution of each FD-factor group to the overall aroma. Especially α-pinene, limonene, γ-terpinene, and 7-methoxycoumarin contribute significantly to the distinct aroma profile of C. latifolia. Heptadecanal (CAS 629-90-3) was described for the first time as an odor-active substance in an enriched C. latifolia peel oil. Campherenyl acetate (CAS 18530-07-9) was identified in nature for the first time and described with a herbal, minty and citrus-like odor. The odor profile of the final recombinant mixture, containing 36 components, was similar to cold-pressed C. latifolia peel oil for most descriptors, whereas the taste profile was described as more aldehydic and citral-like.

Sensory Impact of Novel Dihydrocoumarins in Native Lime Oils.

Citrus fruits have been known and valued for their aroma in food and perfume ever since humans have maintained written records. Often described as the "champagne" of citrus oils, especially cold pressed lime peel oils have raised attention. Particularly peel oils of Citrus latifolia exhibit a pleasant coumarinic, sweet, and balsamic aroma in comparison to its close relative, the Citrus aurantifolia. Those coumarinic notes have not been completely understood until today. Thus, this study aimed to identify the responsible substances and elucidate their contribution and impact on the aroma of cold-pressed lime oil. By combining distillation, fractionation, olfactory detection, and structure elucidation, the responsible key aroma components were identified. A combination of coumarins and their corresponding saturated analogs have been identified to significantly contribute to the typical coumarinic-like aroma, including three new flavor compounds that have not yet been described in the literature as lime oil constituents: 7-methoxy-2-chromanone (3,4-dihydro-7-methoxy-2H-1-benzopyran-2-one; CAS 20921-02-2), 5,7-dimethoxy-2-chromanone (3,4-dihydro-5,7-dimethoxy-2H-1-benzopyran-2-one; CAS 82243-01-4) and 5,6-dihydrobergaptene (5,6-dihydro-4-methoxy-7H-furo[3,2-g][1]benzopyran-7-one; CAS 29050-61-1). The sensorial evaluation of the impact of these components on the lime aroma profile has shown flavor-modulating effects and the ability to enhance aldehydic-peely, juicy, and fruity notes as well as their importance in reproducing the authentic, typical coumarin-like notes.

Antibiotic Conjugates with an Artificial MECAM-Based Siderophore Are Potent Agents against Gram-Positive and Gram-Negative Bacterial Pathogens.

The development of novel drugs against Gram-negative bacteria represents an urgent medical need. To overcome their outer cell membrane, we synthesized conjugates of antibiotics and artificial siderophores based on the MECAM core, which are imported by bacterial iron uptake systems. Structures, spin states, and iron binding properties were predicted in silico using density functional theory. The capability of MECAM to function as an effective artificial siderophore in Escherichia coli was proven in microbiological growth recovery and bioanalytical assays. Following a linker optimization focused on transport efficiency, five ß-lactam and one daptomycin conjugates were prepared. The most potent conjugate 27 showed growth inhibition of Gram-positive and Gram-negative multidrug-resistant pathogens at nanomolar concentrations. The uptake pathway of MECAMs was deciphered by knockout mutants and highlighted the relevance of FepA, CirA, and Fiu. Resistance against 27 was mediated by a mutation in the gene encoding ExbB, which is involved in siderophore transport.

Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor-Rationale and Design of the IMAD Pilot Study.

BACKGROUND: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease. The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer's clinical syndrome within a one-year follow-up period. METHODS: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study. If cognition capacity of eligible patients scores 19-26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement. We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients. The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months. CONCLUSION: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer's clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters.

Improving Medication Adherence With Telemedicine for Adults With Severe Mental Illness.

OBJECTIVE: The study evaluated a telephone call and text message intervention to improve adherence to medication among patients with severe mental illness. METHODS: A randomized clinical trial was conducted, and outpatients with schizophrenia or bipolar disorder were assigned to the intervention group or to a usual care control group. The intervention was provided by trained nurses. Medication adherence was measured with the Medication Adherence Report Scale. RESULTS: The study sample comprised 120 participants. Logistic regression analysis showed that intervention group participants were significantly more likely than control group participants to be medication adherent at 6 months (odds ratio=4.11, p=.007). The superiority of the intervention emerged during months 4 to 6. Social desirability, diagnosis, and medication did not affect the results. CONCLUSIONS: Telemedicine via telephone can deliver low-threshold support to patients who are otherwise at high risk of progressive nonadherence to their psychotropic medication after 6 months.

Prevalence and Determinants of Agonistic Autoantibodies Against α1-Adrenergic Receptors in Patients Screened Positive for Dementia: Results from the Population-Based DelpHi-Study.

BACKGROUND: There is a need to assess promising biomarkers for diagnosis and treatment response in real-life settings. Despite the important role of vascular risk factors, cardiovascular biomarkers have played a minor role in dementia research. Agonistic autoantibodies (agAAB) directed against G-protein-coupled receptors (GPCR) are discussed as modulators of pathology and clinical manifestation. OBJECTIVE: 1) Describe prevalence of agAAB directed against GPCR, especially agABB against α1-adrenergic receptors (α1-AR-agAAB) and agABB directed against ß2-adrenergic receptors (ß2-AR-agAAB) and 2) identify factors associated with agAAB in people with dementia during routine care. METHODS: Blood samples and data from 95 subjects who screened positive for dementia from a primary care cohort, analyzed using an enzyme-linked immunosorbent assay (ELISA) for detecting agAAB. Sociodemographic and clinical data were assessed, and medical records checked. RESULTS: In 40 (42%) samples, agAAB was detected, with n = 29 (31%) representing α1-AR-agAAB and n = 21 (22%) ß2-AR-agAAB. There was no association between the presence of any antibody and a formal diagnosis of dementia. However, patients with coronary heart disease were more likely (OR = 4.23) to have α1-AR-agAAB than those without coronary heart disease. There were no associations between agAAB and age, sex, education, or cognitive impairment. DISCUSSION: For the first time, we show that autoantibodies have a significant prevalence in people with dementia in a routine care setting. Previous findings were restricted to highly selective samples. We replicated the association between α1-AR-agAAB in patients with coronary heart diseases but were not able to find other factors associated with the presence of agAAB.

Paternal transmission of early life traumatization through epigenetics: Do fathers play a role?

Traumatizing events are known to have consequences for the victim which may lead to the development of several well-known mental disorders. Recent research has shown that traumatic events may affect not only the victims' lives, but also that of their progeny. It is generally accepted that this transmission of trauma occurs through parental behavior; however as has been recently discovered, the effects of trauma may also be inherited due to induced alterations in gene expression. These changes, so called epigenetic modifications, illuminate the interaction between genes and the environment. In contrast to mutations, epigenetic alterations do not change the DNA code, but rather modify the DNA structure, thus being capable of regulating gene expression and in turn making it possible for an individual to genetically respond to environmental changes. There are four possible epigenetic mechanisms: paramutation, DNA methylation, posttranslational modification of histones, and non-coding RNA. All of these mechanisms can be found both in somatic cells and in germ cells, leading to the putative transmission of alterations upon fertilization. To date, little is known regarding the epigenetic inheritance of trauma in humans. In this review, we elucidate the hypothesis that males may transmit biological correlates of traumatization through the germline to their offspring. This model of epigenetic inheritance has been supported by some evidence from animal studies. Overall, by considering findings on the epigenetic inheritance of traumatizing events in other mammals as well as findings on epigenetic transmission of acquired traits in humans, it should be possible through future research to confirm the transmission of traumatic effects in humans. By doing so, new possibilities of trauma treatment through modulation of epigenetic pathways might arise.