Barriers and needs in mental healthcare of adults with autism spectrum disorder in Germany: a qualitative study in autistic adults, relatives, and healthcare providers.

BACKGROUND: Autism refers to a neurodevelopmental condition with characteristic impairments in social interaction and communication, restrictive and repetitive behaviors, as well as difficulties in sensory information processing and daily living skills. Even though symptoms persist from early childhood throughout the lifespan and often require long-term support, there is a lack of mental health services that sufficiently meet the needs of autistic adults. Previous evidence suggested individual, professional and structural barriers to healthcare for autistic adults. Here, using a peer research approach, we sought to systematically investigate barriers and needs in mental healthcare of autistic adults in Germany at the three relevant levels (individual, professional, structural) and from three relevant perspectives (autistic adults, relatives and healthcare providers), in order to obtain specific recommendations for optimized healthcare. METHODS: Maximum variation sampling was used to account for the complexity of the research field. Semi-structured, open-ended interviews were conducted with autistic adults (n = 15) and focus groups with relatives/partners (n = 12), and healthcare providers of several professions (n = 15). Data analysis was performed using the codebook approach of thematic analysis. RESULTS: Poor mental healthcare of autistic adults in Germany was characterized by six central and overarching themes: (i) lack of knowledge about autism, (ii) a need for increased participation/involvement, (iii) consideration of autism-specific needs in treatment, (iv) lack of services, (v) limited access to services, and (vi) improvement of stakeholder collaboration. Themes were similarly reported across participants, emphasizing dissatisfaction in all stakeholders. CONCLUSIONS: We identified major barriers to mental healthcare for autistic adults in Germany that affect autistic adults, but are also of concern to relatives and healthcare providers. Our results point to specific and generic areas for improvement, independent of stakeholder perspectives, which could guide future development of needs- and evidence-based services, recommendations and guidelines of mental healthcare for people with autism across the lifespan. TRIAL REGISTRATION: This study protocol was preregistered at the Open Science Framework ( https://osf.io/5x8pg ).

Excess costs of mental disorders by level of severity.

INTRODUCTION: Mental disorders are highly prevalent in Germany, and associated with decreased quality of life for those affected as well as high economic burden for the society. The purpose of this study was to determine the excess costs of mental disorders and to examine how these differ with respect to disease severity. METHODS: We analyzed mean 6-month costs using the baseline data from the RECOVER trial in Hamburg, Germany, which evaluates an innovative stepped-care model for mental disorders. Four severity levels were classified based on the current level of mental illness, loss of functioning, and psychiatric diagnosis. In this work, direct costs (outpatient, inpatient, and social/informal care) and indirect costs (sick leave, unemployment, and early retirement) were estimated using interview-based data on health care utilization and productivity losses. Excess costs were determined by matching a comparison group of the German general population without mental disorders. Group differences in sociodemographic covariates and somatic comorbidities were balanced using entropy balancing. Excess costs by severity levels were estimated using generalized linear models (GLM) with gamma distribution and log-link function. RESULTS: Overall, the RECOVER group included n = 816 and the comparison group included n = 3226 individuals. Mean total 6-month excess costs amounted to 19,075€, with higher indirect excess costs (13,331€) than direct excess costs (5744€) in total excess costs. The excess costs increased with increasing disease severity, ranging from 6,123€ with mild disease severity (level 1) to 31,883€ with severe mental illness (level 4). Indirect excess costs ranged from 5612€ in level 1 to 21,399€ in level 4, and were statistically significant for all disease severity levels. In contrast, direct excess costs were only statistically significant for the levels 2 to 4, and ranged from 511€ in level 1 to 10,485€ in level 4. The main cost drivers were hospital stays (level 2-4), sick leave and unemployment (all levels), and early retirement (level 3-4). DISCUSSION: Mental disorders are associated with high costs that increase with the level of disease severity, which was also shown for individual ICD-10 diagnosis groups. Due to their influence on costs, indirect costs and disease severity levels should be considered in future cost-of-illness studies of mental disorders. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, trial registration number NCT03459664.

Health-related quality of life in family caregivers of autistic adults.

Introduction: Family members of autistic individuals often provide support for their autistic relative throughout the lifespan which can lead to massive burden themselves. Reduced health-related Quality of Life (HRQoL) in family caregivers is assumed; however, only a handful studies on the HRQoL of family caregivers providing care to adult relatives exist as opposed to autistic children. Thus, the current study aimed to (i) investigate the current state of physical and mental HRQoL of family caregivers of autistic adults compared to the general population, and (ii) examine caregiver-related (e.g., age, subjective caregiver burden) and care recipient-related variables (e.g., symptom severity, utilization of formal services) explaining variance in the caregivers' HRQoL. Methods: N = 149 family caregivers completed a nationwide online survey, including the Short-Form Health Survey (SF-8) in order to assess the HRQoL. T-tests were used to compare the HRQoL of family caregivers with the general population. Bivariate correlational and multiple linear regression analyses were conducted in order to identify predictors explaining variance in family caregivers' HRQoL. Results: Family caregivers of autistic adults reported significantly lower physical (M = 46.71, SD = 8.72, Cohen's d = 0.42) and mental HRQoL (M = 40.15, SD = 11.28, Cohen's d = 1.35) compared to the general population. Multiple linear regression with the mental HRQoL as the outcome showed a significant model (F(11, 95) = 5.53, p < .001, adj. R2 = .32) with increased subjective burden explaining most of the variance in mental HRQoL (ß = .32, GDW = .141, p < .001). Multiple linear regression analysis with the outcome physical HRQoL did not reveal a statistically significant model (F(11,95) = 1.09, p = .38). However, bivariate analyses also showed a positive correlation with the subjective caregiver burden (r= .20, p < .05). Discussion: Findings highlight the need to consider HRQoL (and caregiver burden) of family caregivers of autistic adults in several healthcare settings to monitor a potential comprised health status in early stages, with the long-term goal to improve family caregivers' HRQoL.

Mixed-methods investigation of barriers and needs in mental healthcare of adults with autism and recommendations for future care (BarrierfreeASD): study protocol.

INTRODUCTION: Autism refers to an early-onset neurodevelopmental condition with characteristic impairments and difficulties in practical living skills, which persist across the lifespan such that adults with autism often require substantial support and comprehensive care. Yet, mental health and other services are frequently unavailable for adults with autism despite considerable need for mental healthcare and individual, familial and socioeconomic burdens. This study will (1) examine current needs, barriers and burdens related to ineffective healthcare of adults with autism in Germany, (2) develop specific recommendations for a need-oriented mental healthcare model and (3) evaluate its future implementation. METHODS AND ANALYSIS: A mixed-methods design with three phases will be conducted. In phase 1, current mental healthcare for adults with autism will be assessed at three levels (individual, structural and professional) and from three perspectives (adults with autism, relatives and healthcare providers) using (1) focus groups/interviews (qualitative data) and (2) large-scale online surveys (quantitative data). Furthermore, service utilisation and related costs will be estimated. In phase 2, recommendations for a future healthcare model will be derived based on phase 1, considering the heterogeneous and complex needs within the autism spectrum and specifying indications for recommended services. In phase 3, these will again be evaluated by the three stakeholder groups using mixed-methods and analysed regarding feasibility of implementation and cost-effectiveness. Our study will, thus, contribute to a better translation of recommendations into practice to reduce disability, burden and costs related to ineffective healthcare and improve mental health outcomes for adults with autism and those who support them. ETHICS AND DISSEMINATION: This study was approved by the Local Psychological Ethics Commission of the Center for Psychosocial Medicine at the University Medical Center Hamburg-Eppendorf (LPEK-0227). Findings will be disseminated via scientific meetings and peer-reviewed journals. Cooperating partners and associations will be informed about the study's course and findings by regular newsletters and meetings. TRIAL REGISTRATION NUMBER: This study protocol was preregistered at the Open Science Framework (osf.io/5x8pg).

Excess costs of type 2 diabetes and their sociodemographic and clinical determinants: a cross-sectional study using data from the German Health Interview and Examination Survey for Adults (DEGS1).

OBJECTIVES: The objectives of this study were to estimate the direct and indirect excess costs of type 2 diabetes mellitus (T2D) using data representative for the German adult population and to investigate the association of sociodemographic and clinical determinants with these excess costs. SETTING: We calculated mean annual costs for individuals with T2D and a control group without diabetes, using data on healthcare utilisation and productivity losses from the cross-sectional German Health Interview and Examination Survey for Adults. We adjusted for group differences using entropy balancing and estimated excess costs for total, direct, indirect costs and additional cost categories using generalised linear models. We performed subgroup analyses to investigate the association of sociodemographic (age, sex and education) and clinical determinants (diabetes duration, glycaemic index and complications) with excess costs. PARTICIPANTS: The final study sample included n=325 individuals with T2D and n=4490 individuals without diabetes in the age between 18 and 79 years. RESULTS: Total excess costs amounted to €927, of which €719 were attributable to direct and €209 to indirect excess costs. Total costs were significantly increased by 28% for T2D compared with controls. Group differences in direct, outpatient and medication costs were statistically significant. Medication costs were 88% higher for T2D and had the highest share in direct excess costs. With respect to specific determinants, direct excess costs ranged from €203 for 4-10 years diabetes duration to €1405 for diabetes complications. Indirect excess costs ranged from €-544 for >10 years diabetes duration to €995 for high education. CONCLUSIONS: T2D was associated with high costs, mainly due to direct costs. As pointed out by our results, diabetes complications and comorbidities have a large impact on the costs, leaving medication costs as main contributor of T2D excess costs.

The Excess Costs of Depression and the Influence of Sociodemographic and Socioeconomic Factors: Results from the German Health Interview and Examination Survey for Adults (DEGS).

INTRODUCTION: The aim of this study was to estimate excess costs of depression in Germany and to examine the influence of sociodemographic and socioeconomic determinants. METHODS: Annual excess costs of depression per patient were estimated for the year 2019 by comparing survey data of individuals with and without self-reported medically diagnosed depression, representative for the German population aged 18-79 years. Differences between individuals with depression (n = 223) and without depression (n = 4540) were adjusted using entropy balancing. Excess costs were estimated using generalized linear model regression with a gamma distribution and log-link function. We estimated direct (inpatient, outpatient, medication) and indirect (sick leave, early retirement) excess costs. Subgroup analyses by social determinants were conducted for sex, age, socioeconomic status, first-generation or second-generation migrants, partnership, and social support. RESULTS: Total annual excess costs of depression amounted to €5047 (95% confidence interval [CI] 3214-6880) per patient. Indirect excess costs amounted to €2835 (1566-4103) and were higher than direct excess costs (€2212 [1083-3341]). Outpatient (€498), inpatient (€1345), early retirement (€1686), and sick leave (€1149) excess costs were statistically significant, while medication (€370) excess costs were not. Regarding social determinants, total excess costs were highest in the younger age groups (€7955 for 18-29-year-olds, €9560 for 30-44-year-olds), whereas total excess costs were lowest for the oldest age group (€2168 for 65+) and first-generation or second-generation migrants (€1820). CONCLUSIONS: Depression was associated with high excess costs that varied by social determinants. Considerable differences between the socioeconomic and sociodemographic subgroups need further clarification as they point to specific treatment barriers as well as varying treatment needs.

Study protocol for a randomised controlled trial evaluating an evidence-based, stepped and coordinated care service model for mental disorders (RECOVER).

INTRODUCTION: Healthcare systems around the world are looking for solutions to the growing problem of mental disorders. RECOVER is the synonym for an evidence-based, stepped and cross-sectoral coordinated care service model for mental disorders. RECOVER implements a cross-sectoral network with managed care, comprehensive psychological, somatic and social diagnostics, crisis resolution and a general structure of four severity levels, each with assigned evidence-based therapy models (eg, assertive community treatment) and therapies (eg, psychotherapy). The study rationale is the investigation of the effectiveness and efficiency of stepped and integrated care in comparison to standard care. METHODS AND ANALYSIS: The trial is conducted in accordance to the Standard Protocol Items: Recommendations for Interventional Trials Statement. The study aims to compare the RECOVER model with treatment as usual (TAU). The following questions are examined: Does RECOVER reduce healthcare costs compared with TAU? Does RECOVER improve patient-relevant outcomes? Is RECOVER cost-effective compared with TAU? A total sample of 890 patients with mental disorders will be assessed at baseline and individually randomised into RECOVER or TAU. Follow-up assessments are conducted after 6 and 12 months. As primary outcomes, cost reduction, improvement in symptoms, daily functioning and quality of life as well as cost-effectiveness ratios will be measured. In addition, several secondary outcomes will be assessed. Primary and secondary outcomes are evaluated according to the intention-to-treat principle. Mixed linear or logistic regression models are used with the direct maximum likelihood estimation procedure which results in unbiassed estimators under the missing-at-random assumption. Costs due to healthcare utilisation and productivity losses are evaluated using difference-in-difference regressions. ETHICS AND DISSEMINATION: Ethical approval from the ethics committee of the Hamburg Medical Association has been obtained (PV5672). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications. TRIAL REGISTRATION NUMBER AND REGISTRY NAME: ClinicalTrials.gov (NCT03459664), RECOVER PROTOCOL VERSION: 19 March 2020 (V.3.0).

Economic Burden of Anxiety Disorders: A Systematic Review and Meta-Analysis.

BACKGROUND: Anxiety disorders (AD) are common mental disorders, for which several cost-of-illness (COI) studies have been conducted in the past. OBJECTIVE: The aim of this review was to provide a systematic overview of these studies and an aggregation of their results. METHODS: A systematic literature search limited to studies published after 1999 was conducted in PubMed/MEDLINE in November 2018. We included top-down COI studies reporting costs for AD, and bottom-up COI studies reporting costs for AD and a non-diseased control group, and extracted data manually. Results of the top-down COI studies were aggregated by calculating the mean percentage of costs on gross domestic product (GDP) and health expenditure, while the results of the bottom-up studies were analyzed meta-analytically using the 'ratio of means' method and inverse-variance pooling. In this review, the logarithm of the relative difference in a continuous outcome between two groups is calculated and aggregated over the studies. The results can be interpreted as the relative change in costs imposed by a specific disease compared with baseline costs. RESULTS: We identified 13 top-down and 11 bottom-up COI studies. All top-down COI studies and four bottom-up COI studies reported costs for AD as a diagnostic group, four for generalized anxiety disorder (GAD), four for social anxiety disorder (SAD), and one for panic disorder. In top-down COI studies, direct costs of AD, on average, corresponded to 2.08% of health care costs and 0.22% of GDP, whereas indirect costs, on average, corresponded to 0.23% of GDP. In bottom-up COI studies, direct costs of patients with AD were increased by factor 2.17 (1.29-3.67; p = 0.004) and indirect costs were increased by factor 1.92 (1.05-3.53; p = 0.04), whereas total costs increased by factor 2.52 (1.73-3.68; p < 0.001). Subgroup analysis revealed an increase in direct costs by 1.60 (1.16-2.22; p = 0.005) for SAD and 2.60 (2.01-3.36; p < 0.001) for GAD. Measures of heterogeneity indicated high heterogeneity when pooling studies for direct costs, indirect costs, and total costs, but low to moderate heterogeneity when pooling studies for SAD or GAD. CONCLUSIONS: Using methods that focused on relative rather than absolute costs, we were able to aggregate costs reported in different COI studies for ADs. We found that ADs were associated with a low proportion of health care costs on a population level, but significantly increased health care costs on an individual level compared with healthy controls. Our disorder-specific subgroup analysis showed that study findings are most homogeneous within specific ADs. Therefore, to get a more detailed picture of the costs of ADs, more studies for currently under researched ADs, such as panic disorder, are needed.

Synthesis of nanometer-sized rod-coil block copolymers.

We present the solid-supported synthesis of a linear rigid rod-like tetradeca(p-benzamide) nanorod as well as a pentadeca( p -benzamide) nanorod carrying an amide N-hexyl side chain at the center of the rod (on the 8(th) amino acid of the molecule). These nanorods were conjugated with solubilizing poly(ethylene glycol) chains and their solution aggregation was investigated. Both rod-coil block copolymers form soluble aggregates even in polar aprotic solvents such as DMF and DMSO. We show that sequence-controlled nanometer-sized shape persistent aramide scaffolds can readily be prepared using solid-supported synthesis.

Janus micelles induced by olefin metathesis.

A facile one-step procedure for hydrophobic modification and simultaneous TEM contrast enhancement via a regioselective olefin metathesis reaction using Grubbs' catalyst is presented. Polyether diblock copolymers were investigated, and both the chain ends of the hydrophilic and the hydrophobic block were hydrophobically modified. Modification of the hydrophilic block results in nonsymmetric supramolecular structures (Janus micelles) which self-assemble into larger hierarchically organized super-micelles.

Learning from nature: beta-sheet-mimicking copolymers get organized.

The solution structures formed by coil-coil copolymers arise from the selective solvation of one of the two blocks and have been well described. In most cases in such relatively simple synthetic structures there are no specific attractive forces that can aid the aggregation process. Nature, however, provides plenty of inspiring polymeric architectures that are shaped and ordered hierarchically by noncovalent forces. The high level of structural definition displayed by proteins, for example, is unmatched by synthetic polymers. An emerging area of interest in polymer science tries to combine the best of both worlds, the natural and the synthetic, by conjugating synthetic polymers and beta-sheet-forming peptides. Understanding the supramolecular organization of the block copolymers driven exclusively by the intermolecular attractive forces of the peptide sequence is of particular interest. Not only do these peptide-polymer hybrid structures present an interesting new class of materials, they can also provide important insights into self-organization processes prevalent in nature.

Supramolecular PEG-co-oligo(p-benzamide)s prepared on a peptide synthesizer.

An automated synthesis protocol has been developed for the preparation of oligo(p-benzamide)s on solid support using a commercial peptide synthesizer employing a variation of standard Fmoc chemistry. Bis(trichloromethyl carbonate) in NMP was used to activate the aromatic carboxylic acids for acylation of secondary aromatic amines on solid support. N-Protected hepta(p-benzamide) was automatically prepared on solid support and manually converted to a solid supported block co-oligomer by attaching a poly(ethylene glycol) chain. Cleavage from the support could be achieved with minimal loss of the p-methoxybenzyl N-protective group. While the N-protected block co-oligomer was molecularly dissolved in nonpolar organic solvents, the N-deprotected block co-oligomer adopted a rod-coil conformation and showed strong aggregation as evidenced by gel permeation chromatography and transmission electron microscopy. Rigid rodlike aggregates could be observed in chloroform, toluene, as well as water.

Solid-phase synthesis of oligo(p-benzamide) foldamers.

[reaction: see text] A coupling protocol has been developed which allows the synthesis of oligo(p-benzamide)s on solid support. Aromatic carboxylic acids are activated in situ with thionyl chloride and used to acylate secondary aromatic amines. N-p-Methoxy benzyl (PMB) as well as N-hexyl protected monomers were investigated. Heterosequences of both monomers were synthesized. Such nanoscale objects are important building blocks for supramolecular chemistry.