Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design.

Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99-5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1-2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02-3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

Determinants for participation in a prevention and early detection programme for children and adolescents in Germany: does social background play a role?

Early detection examinations and prevention are particularly important in childhood and adolescence, as certain diseases are already developing and health-related attitudes and behaviour patterns are formed and implemented. Despite the importance of screening and prevention, not all families use the available services and programmes. The aim of this study is to identify factors associated with participation in an early detection and prevention programme for children and adolescents, as well as factors associated with actual uptake of an examination. The analyses are based on questionnaire data of an online survey of participants and non-participants. Descriptive analyses and logistic regression models are conducted on a defined sample (n = 1,289). The results show that both groups differ with regard to several factors: age, chronic diseases, federal state, living space, number of siblings, country of birth, migration background, language spoken at home, mother's occupational status, household income, treatment duration, and trust in treating physician. Regression I shows that participation in the programme is significantly associated with higher age, language spoken at home, mother's occupational status and greater trust in the treating physician. The latter demonstrates the highest predictive power. Regression II indicates that the actual uptake of an examination among participants is significantly affected by age, federal state and father's occupational status. Overall, the results of this study show that social background partly plays a role in participation, but that factors such as trust in the treating physician also have a significant impact. For the future, further research on the factors influencing participation in screening and prevention services or programmes for children and adolescents is important in order to develop strategies to overcome existing barriers and thus reach groups that have not been reached yet. In this context, trust in the treating physician and his or her influence on decision-making should in particular be considered.

The effectiveness of additional screening examinations for children and adolescents in Germany: a longitudinal retrospective cohort study.

BACKGROUND: Continuous medical care is particularly important in childhood and adolescence. Since there are gaps in regular care in Germany, various health insurance providers offer to cover additional examinations (e.g., U10, U11, J2) to ensure ongoing paediatrician visits. However, the question arises as to whether these examinations are effective. Thus, the main objective of this study is to determine whether participation in the U10, U11 or J2 examinations leads to more frequent and earlier diagnosis and treatment of age-specific diseases. METHODS: The analyses are based on administrative claims data from a statutory health insurance fund. For each examination, an intervention group (IG) is formed and matched with a corresponding control group (CG). Descriptive analyses include proportion with diagnosis and treatment, average age of diagnosis and treatment initiation. Hypothesis testing is performed using methods appropriate to each. In addition, subgroup analyses and binominal logistic regression models are conducted. RESULTS: More diagnoses are detected in IG, irrespective of subgroups. Additionally, diagnoses are made slightly earlier on average in IG. In the total samples, more therapies are initiated in IG, and slightly earlier. Considering only diagnosed cases, more therapies are initiated in CG but continue to be started earlier in IG. Regression models show that participation in the examinations has the highest predictive power for detecting a diagnosis. The presence of a chronic disease and sex - male at the U10 and U11 and female at the J2 - are also significantly associated. The models further show that nationality, unemployment of parents and region also have a significant influence in some cases, whereas school-leaving qualification, vocational qualification and income of parents do not. Considering the initiation of treatment in overall samples, the models show similar results, but here the presence of a chronic illness has the highest predictive power. CONCLUSION: The results indicate that participation in the examinations leads to significantly more diagnoses and, in the overall samples, significantly more treatments. In addition, diagnoses were made somewhat earlier and therapies were initiated somewhat earlier. In the future, it would be useful to investigate the U10, U11 and J2 examinations over a longer time horizon to determine whether the statistically significant difference found is also clinically relevant, i.e., earlier diagnosis and initiation of therapy lead to prevention of manifestation or progression of the diagnosed diseases and to avoidance of secondary diseases. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS-ID: DRKS00015280. Prospectively registered on 18 March 2019.

[Quality of Life and Experienced Distress of Patients Suspected of having a Rare (Chronic) Health Condition - Initial Findings from the ZSE-DUO Study]. / Lebensqualität und erlebte Belastungen von Patient*innen mit Verdacht auf eine Seltene Erkrankung ­ erste Erkenntnisse aus der ZSE-DUO Studie.

OBJECTIVE: Patients suspected of having a rare (chronic) health condition have often gone a long way within the healthcare system. To date, little is known about the health-related quality of life of this group of patients. The study aims to describe the health-related quality of life and the perceived distress of patients suspected of having a rare (chronic) health condition and compare the results with standard values of the German population. METHODS: Eighty patients suspected of having a rare (chronic) health condition were recruited in the nationwide intervention study "ZSE-DUO" and reported their health-related quality of life and perceived distress using the SF-8 and the Distress-Thermometer. RESULTS: The patients rated all eight dimensions of quality of life as well as the physical and mental component scores of the SF-8 significantly lower than the general population. On average, the perceived distress was rated significantly higher. More than 90% of the sample indicated distress in the clinical range. Exhaustion, pain, limited mobility as well as worries and fears were mentioned most frequently as concrete problems, with percentages ranging from 73% to 90% of the total sample. DISCUSSION: In comparison to German reference data, patients suspected of having a rare (chronic) health condition report a massive impairment of their quality of life and a high burden, which is especially characterized by physical and emotional problems. The lack of a diagnosis could explain the high proportion of emotional problems, as it can create a form of legitimation of one's own disease experience. CONCLUSION: The present results underline the need for research on the psychosocial impact of the possible presence of a rare (chronic) health condition. The high distress and the impact on the physical and psychological quality of life domains also highlight the need for care in this patient group.

Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study.

BACKGROUND: In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. STUDY DESIGN: This multi-center, prospective controlled study has a two-phase cohort design. METHODS: Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD's outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). OUTCOMES: Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients' quality of life and evaluation of care; and f) physicians' satisfaction with the innovative care approach. CONCLUSIONS: This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. Trial registration ClinicalTrials.gov; Identifier: NCT03563677; First posted: June 20, 2018, https://clinicaltrials.gov/ct2/show/NCT03563677 .