Epidemiology and economic burden of meningococcal disease in Germany: A systematic review.

INTRODUCTION: Invasive meningococcal disease (IMD) is a notifiable disease in Germany and other European countries. Due to the high lethality of the disease and the risk of long-term consequences, IMD prevention is of high public health relevance despite the low number of cases in the population. This study aims to describe key epidemiological and economic parameters of IMD in Germany to support national decision-making processes for implementing enhanced prevention measures. METHODS: Based on a systematic literature review in PubMed and EMBASE, all publications on the burden of disease and costs of IMD published up to May 2020 were evaluated. Additionally, notification data were used to report the annual case numbers and incidence of IMD in Germany until the end of 2019. RESULTS: Thirty-six studies were included, of which 35 reported data on the epidemiological burden of disease and three reported data on economic aspects of IMD. The type of reported endpoints and results on the incidence of IMD differed widely by reporting year, population, and data source used. Most of the data are reported without specific information about a serogroup. Data on the economic burden of disease and healthcare resource use are scarce. Based on mandatory notification data, a decrease in the incidence of notified IMD cases has been observed since 2004. Currently, the nationwide annual incidence in Germany is at 0.3 cases per 100,000 persons and has gradually decreased. While the overall decline is mainly attributable to MenB, cases with MenY and MenW are the only ones that have increased on a low level in recent years. CONCLUSION: While IMD is a rare disease, high direct and indirect costs illustrate the relevance of the disease for patients, caregivers, as well as for the health care system. Future research should concentrate on quantifying the long-term economic burden and indirect costs of meningococcal disease. Integrated IMD surveillance with isolate characterisation remains crucial to inform public health policies.

Clinical burden of illness in patients with phenylketonuria (PKU) and associated comorbidities - a retrospective study of German health insurance claims data.

BACKGROUND: Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany. METHODS: This retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ≥18 years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values. RESULTS: The analysis included 377 adult PKU patients (< 5 of which were receiving sapropterin dihydrochloride) and 3,770 matched controls. Of the 50 most common comorbidities in the PKU population, those with a statistically significant PR > 1.5 vs controls included major depressive disorders (PR = 2.3), chronic ischemic heart disease (PR = 1.7), asthma (PR = 1.7), dizziness and giddiness (PR = 1.8), unspecified diabetes mellitus (PR = 1.7), infectious gastroenteritis and colitis (PR = 1.7), and reaction to severe stress and adjustment disorders (PR = 1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%). CONCLUSION: The overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease).

Methods for measuring financial toxicity after cancer diagnosis and treatment: a systematic review and its implications.

Patients experiencing financial distress as a side-effect of cancer are not only reported in the United States, but also in third-party payer healthcare systems in Europe. Since validated survey instruments are a prerequisite for robust and comparable results, we aimed to compile and classify available instruments to enable both a better understanding of the underlying construct of financial toxicity and to facilitate further studies that are adjustable to various healthcare systems. We did a systematic literature search on studies that provide data on perceived cancer-related financial distress experienced by adult patients using PubMed, CINAHL and Web of Science databases up to 2018. We analyzed all detected instruments, items domains and questions with regard to their wording, scales and the domains of financial distress covered. Among 3298 records screened, 41 publications based on 40 studies matched our inclusion criteria. Based on the analysis of 352 different questions we identified 6 relevant subdomains that represent perceptions of and reactions to experienced financial distress: (i) active financial spending, (ii) use of passive financial resources, (iii) psychosocial responses, (iv) support seeking, (v) coping with care or (vi) coping with ones' lifestyle. We found an inconsistent coverage and use of these domains that makes it difficult to compare and quantify the prevalence of financial distress. Moreover, some existing instruments do not reflect relevant domains for patients in third-party payer systems. There is neither a consistent understanding of the construct of financial burden nor do available instruments cover all relevant aspects of a patients' distress perception. We encourage using the identified six domains to further develop survey instruments and adjust them to different health systems.

[Psychotherapy and psychological procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Psychotherapie und psychologische Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature for systematic reviews of randomized, controlled studies on psychological and psychotherapeutic procedures from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Cognitive behavioral therapies received a strong recommendation but biofeedback, guided imagery and hypnosis received a weak recommendation.

[Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017, overview of systematic review articles and overview of studies on small fiber neuropathy in FMS subgroups]. / Ätiologie und Pathophysiologie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten sowie eine Übersicht über Studien zur Kleinfaserpathologie bei Subgruppen des FMS.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was planned for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Prospective population-based studies and systematic reviews with meta-analyses of case control studies were taken into consideration for the statements. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The statements were generated by multiple step formalized procedures. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS: Current data do not enable identification of distinct factors in the etiology and pathophysiology of fibromyalgia syndrome. Fibromyalgia syndrome can be associated with inflammatory rheumatic diseases, gene polymorphisms, life style factors (e.g. smoking, obesity and lack of physical activity), depressive disorders as well as physical and sexual abuse in childhood and adulthood. CONCLUSION: Fibromyalgia syndrome is most probably the end result of various pathogenetic factors and pathophysiological mechanisms.

[FIMA--questionnaire for health-related resource use in an elderly population: development and pilot study]. / FIMA--Fragebogen zur Erhebung von Gesundheitsleistungen im Alter: Entwicklung und Pilotstudie.

AIM: Due to demographic trends towards an ageing population resource use of health care will increase. By collecting health-related costs via questionnaires, the impact of socio-economic variables and other medical factors can be examined. In addition, only patient reported resource use accounts for out-of-pocket payments. Thus, it is necessary to develop an appropriate tool to collect the health-related resource use in an elderly population. METHODS: The development of the FIMA (questionnaire for the use of medical and non-medical services in old age) was carried out in 6 steps. These included the determination of necessary questionnaire contents based on a literature review and the wording and layout were defined. Finally the questionnaire was tested in a pilot study and was modified. RESULTS: All direct medical and non-medical resource use excluding transportation and time costs were recorded. Productivity losses were not included. The recall time frames differed according to resource categories (7 days, 3 months, 12 months). For the pilot study, 63 questionnaires were analysed. The response rate was 69%. The questionnaire took an average of 21 min to complete. Three quarters of respondents completed the questionnaire without help and 90% rated the difficulty as easy or even very simple. There was good agreement between self-reported health-related quality of life and the resource use of nursing and domestic help (phi coefficient values between 0.52 and 0.58). CONCLUSION: The FIMA is a generic questionnaire which collects the health-related resource use within the older population groups.

[Calculation of standardised unit costs from a societal perspective for health economic evaluation]. / Ermittlung standardisierter Bewertungssätze aus gesellschaftlicher Perspektive für die gesundheitsökonomische Evaluation.

PURPOSE: Due to demographic aging, economic evaluation of health care technologies for the elderly becomes more important. A standardised questionnaire to measure the health-related resource utilisation has been designed. The monetary valuation of the resource use documented by the questionnaire is a central step towards the determination of the corresponding costs. The aim of this paper is to provide unit costs for the resources in the questionnaire from a societal perspective. METHODS: The unit costs are calculated pragmatically based on regularly published sources. Thus, an easy update is possible. RESULTS: This paper presents the calculated unit costs for outpatient medical care, inpatient care, informal and formal nursing care and pharmaceuticals from a societal perspective. CONCLUSION: The calculated unit costs can serve as a reference case in health economic evaluations and hence help to increase their comparability.

Economic burden of neural tube defects in Germany.

OBJECTIVE: Failure of closure of the neural tube often leads to serious malformations, including spina bifida, anencephaly and encephalocoele. Despite improvements in medical and surgical treatment, the burden associated with spina bifida is substantial but country-specific data are lacking outside North America. This study aims to improve understanding of the economic implications and burden associated with the morbidity of children and adults with neural tube defects (NTDs) in Germany. STUDY DESIGN: Retrospective data analysis. METHODS: 2006-2009 German health insurance data of persons with NTDs (spina bifida and encephalocoele) were analysed to determine the economic burden of illness associated with NTDs in Germany. Cases were identified using ICD-10 codes; data included outpatient and inpatient care, rehabilitation, remedies and medical aids, pharmacotherapy use, long-term care and information on sick leave. The analysis was stratified by age group to provide a burden estimate specific to a person's age. To obtain an indicator of incremental burden to the Statutory Health Insurance (SHI), results were compared to the standardized healthcare expenditures according to the German Risk Compensation Scheme (RSA). RESULTS: Overall, 4141 persons with an ICD code related to NTDs were identified (out of a population of 7.28 million persons screened). The administrative prevalence ranged from 0.54 to 0.58 per 1000 enrollees. Of those, 3952 (95.4%) were diagnosed with spina bifida. The average annual mean healthcare expenditure of persons with spina bifida was €4532 (95% CI = 4375-4689, SD = 9590, Median = 1000), with inpatient care contributing €1358 (30.0%), outpatient care €644 (14.2%), rehabilitation €29 (0.6%), pharmacotherapy €562 (12.4%), and remedies and medical aids €1939 (42.8%). The incremental cost due to spina bifida was substantially higher than the standardized SHI expenditures for all age groups. The difference was highest for persons ≤ 10 years old (€10,971 vs €2360 for the age group ≤ 1, €8599 vs €833 for the age group 2-5 years and €10,601 vs €863 for the age group 6-10 years). The difference was smallest for the age group 41-50 years (€2524 vs €1101) and for 71 years and over (€5278 vs €4389). CONCLUSION: Expenditures of persons with spina bifida exceeded the standardized SHI expenditures, indicating a considerable economic burden. The economic burden is continuous throughout the person's life, with high monetary impact and exposure to the healthcare system (especially in early years of life). Efforts should be devoted to improve the prevention of NTDs and provide appropriate support for persons with NTDs, parents, and caregivers--especially in early years.

Estimating the long-term effects of HPV vaccination in Germany.

In Germany, vaccination against the most oncogenic HPV types 16/18 is recommended by the Standing Committee on Vaccination (STIKO) for 12-17 year old girls since March 2007. We developed a dynamic mathematical model for the natural history and transmission of HPV infections to estimate the impact of vaccination on incidence and mortality of cervical cancer and its pre-stages, and on anogenital warts. We focused on an extensive model calibration to epidemiologic data for all stages of the natural history model as well as on a detailed implementation of cervical cancer screening modalities in Germany. Our model predicts first a substantial reduction of cervical cancer incidence and mortality over the next 30 years, which is mainly attributable to an increase in screening participation in the 1990s and not to HPV vaccination, followed by a further reduction attributable to vaccination. Over the next 100 years, HPV vaccination will prevent approximately 37% of cervical cancer cases even if vaccination coverage is only 50% (as currently observed in Germany). Consideration of cross-protection results in a further reduction of approximately 7% of all cervical cancer cases for the bivalent and about 5% for the quadrivalent vaccine in our model. Vaccination of boys was only reasonable if moderate to high vaccination coverage in girls was not achieved. Strategies should be implemented in Germany to increase HPV vaccination coverage among girls thereby making better use of the demonstrated benefits of the vaccine.

[Economic aspects of integrated care]. / Ökonomische Aspekte der integrierten Versorgung.

For more than 10 years integrated care has been an inherent part of the German healthcare system. The aims of selective contracts are to minimize interface problems between outpatient and inpatient sectors, generalist und specialist care as well as to intensify competition. Despite repeated efforts by the legislator, comprehensive integrated healthcare is still limited to a few flagship projects. This is mainly due to low incentives on the part of both suppliers and customers. Therefore, this article focuses on the economic aspects of integrated care. From a theoretical perspective, integrated care improves efficiency in the healthcare sector by reducing interface problems and asymmetric information as well as by intensifying competition. In practice, however, there are a number of obstacles to implementation. Particularly noteworthy are the financial difficulties in addition to problems regarding sectoral budgeting and the long-term nature of investments. However, the political environment and thus the financial arrangements within the statutory health insurance seem to be more important for further development of integrated care in Germany than the financing issues.

Relationship between multimorbidity and direct healthcare costs in an advanced elderly population. Results of the PRISCUS trial.

OBJECTIVES: The goal of this work was to analyze the impact of the extent of multimorbidity on health service resource utilization and, thus, direct healthcare costs of advanced elderly in the German population. METHODS: Based on a cross-sectional sample aged 72 or above in Germany (n = 1,937), a bottom-up study assessing resource utilization and corresponding costs was performed. Main data sources were patient-reported information concerning morbidity and health service resource utilization administered via telephone interviews within the framework of the PRISCUS trial. To value resource utilization, unit costs were determined for all services under consideration. In order to estimate the impact of multimorbidity on mean annual direct costs, a cumulative multimorbidity index was constructed. Influencing factors on annual average costs were identified via multivariate linear regression models. RESULTS: Mean annual direct costs of 3,315 EUR (95% confidence interval (CI) 3,118; 3,512) at 2010 prices were caused by the involved patients: 25% of mean annual costs were due to inpatient care, 20% to outpatient physician services, 20% to pharmaceuticals, 12% to assisted living and transportation, 8% to healthcare products and dentures, 7% to rehabilitation services, 5% to outpatient nonphysician providers, and 3% to spending from compulsory long-term care insurance. Each additional comorbidity was accompanied by a cost increase of 563 EUR (95% CI 488; 638). Participants with no diseases mentioned in the multimorbidity index caused average annual costs of 1,250 EUR. In contrast, respondents with 10 + diseases caused the highest mean annual costs of 6,862 EUR. CONCLUSION: Longer life expectancy has become commonplace and is often associated with the simultaneous occurrence of several diseases. A clear understanding of the impact of multimorbidity on costs is highly relevant for health policy decision makers. The present study provides a well-founded basis to analyze the relationship between multiple morbidity and associated costs due to healthcare resource consumption of older adults in Germany.

[Linkage of data of the medical service of the health insurances with data of a cancer registry]. / Abgleich von Verwaltungsdaten des Medizinischen Dienstes der Krankenversicherung mit Krebsregisterdaten.

BACKGROUND: The aim of this study was to examine whether a linkage of data sets of the Epidemiological Cancer Registry North Rhine-Westphalia (EKR-NRW) and the Medical Service of the Health Insurances (MDK WL) is feasible, which problems may occur during execution and what could be a solution strategy. METHODS: Data of the EKR-NRW were used to identify all cancer cases in the district of Munster, for which an expert opinion regarding nursing needs from the period 2004-2008 was available at the MDK WL. For this purpose factually anonymised data of the EKR-NRW and the MDK WL were linked by means of a semi-automatic probabilistic record linkage. RESULTS: Data linkage yielded 18 877 cancer cases but required great technical and temporal input. The processing of management data and the use of "routine channels" (ISDN connection), which provide the necessary safety for data transfer, but are designed for a considerably smaller amount of data, accounted for this. The interface problem (converting data from text format to a hierarchical XML format) can be solved with Excel or SAS. CONCLUSION: A record linkage with factually anonymised data from the MDK WL and the EKR-NRW is feasible. This allows, among other things, quantifying the needs for nursing care in persons with a cancer diagnosis.

Heavy-particle radioactivity of superheavy nuclei.

The concept of heavy-particle radioactivity (HPR) is changed to allow emitted particles with Z(e) > 28 from parents with Z > 110 and daughter around (208)Pb. Calculations for superheavy (SH) nuclei with Z = 104-124 are showing a trend toward shorter half-lives and larger branching ratio relative to α decay for heavier SHs. It is possible to find regions in which HPR is stronger than alpha decay. The new mass table AME11 and the theoretical KTUY05 and FRDM95 masses are used to determine the released energy. For 124 we found isotopes with half-lives in the range of ns to ps.

Prerequisites for a new health care model for elderly people with multimorbidity: the PRISCUS research consortium.

BACKGROUND: Multimorbidity, the concurrent manifestation or presence of multiple chronic conditions, poses huge challenges to affected patients, their relatives, physicians, and practitioners alike. The growing number of affected persons and the complexity of their needs places just as much of a burden on the health care system as does the plethora of often poorly coordinated interventions. The Chronic Care Model developed for different chronic diseases is suited for improving medical care. The PRISCUS research consortium was established to create the prerequisites for a new care model for multimorbid, elderly patients oriented along those lines. METHODS: The research consortium utilizes data gathered in a large-scale epidemiological study on peripheral arterial disease (getABI study) and from the Dortmund and Münster stroke registries, by extracting epidemiologic and health economic data, quality-of-life parameters, and data on the extent and quality of medication. Additional projects evaluate the implementation of a multidimensional geriatric assessment in primary care, the functional consequences of multimorbidity in stroke patients along with options for prevention and therapy afforded by physical activity. Systematic reviews of the literature are used to describe quality of life and patient preferences. Experts will work on an initial draft treatment standard for patients with multimorbidity and a list of potentially inappropriate medication for the elderly in Germany. CONCLUSION: The results of the PRISCUS research consortium will enable an epidemiologic characterization and description of consequences of multimorbidity, while illustrating new approaches towards prevention, diagnosis, and management of multimorbid patients. With this, some prerequisites for a new health care model for patients with multimorbidity comparable to the Chronic Care Model will be fulfilled.

[Analysing the work of medical and nursing staff: comparison between PsychPV requirements and everyday activities on psychiatric wards]. / Tätigkeitsanalyse im ärztlichen und pflegerischen Dienst : Abgleich der PsychPV-Vorgaben mit dem Arbeitsalltag auf einer stationären psychiatrischen Einrichtung.

BACKGROUND: Since 1991 the German psychiatry personnel regulation act (PsychPV) defines the number and tasks of medical doctors and nursing staff on a psychiatric ward. However, there is the suspicion that there are differences, especially with regard to an increased proportion of activities not involving patients, such as documentation and administrative work. METHODS: To detect differences between requirements from the PsychPV and the actual amount of time spent on different activities, a task analysis was performed on a general psychiatric and a gerontological psychiatric ward. In this study the proportions of working time spent on five different types of activities with time that should have been spent according to the PsychPV were compared. RESULTS: Discrepancies were found on both psychiatric wards and for medical doctors as well as for nursing staff. Tasks of documentation and administrative work took significantly higher proportions of working time than required in the PsychPV. On the other hand psychiatric personnel spent less time for treatment or nursing in direct contact with the patients. CONCLUSION: The results of this study confirmed the suspicion that shifting tasks on psychiatric wards has led to changed treatment settings.

[Prerequisites for a new health care model for elderly people with multiple morbidities: results and conclusions from 3 years of research in the PRISCUS consortium]. / Voraussetzungen für ein neues Versorgungsmodell für ältere Menschen mit Multimorbidität: Ergebnisse und Schlussfolgerungen aus 3-jähriger Forschung im PRISCUS-Verbund.

BACKGROUND: The concurrent presence or manifestation of multiple chronic conditions, i.e. multimorbidity, poses a challenge to affected patients and their relatives, physicians, and practitioners, and to the health care system in general. Aiming to improve medical care for different chronic diseases, the Chronic Care Model also appears to be suited for multimorbidity. The established research consortium PRISCUS is trying to create some of the prerequisites for a new care model for multimorbid, elderly patients oriented along the lines of the Chronic Care Model. METHODS AND RESULTS: Four out of seven subprojects of the research consortium provide an overview of some of their findings. Topics in a sports medicine subproject were the assessment of physical activity by means of a newly developed questionnaire and the development and feasibility testing of an exercise program for elderly people with chronic conditions and mobility impairment. Partners from family medicine implemented geriatric assessment in a primary care setting and evaluated its consequences. In a pharmacological subproject, potentially inappropriate medication as well as drug-drug interactions and dosing errors were addressed. The health economic subproject investigated quality of life impairment due to multiple chronic diseases and the effects of multimorbidity on costs. CONCLUSIONS: The results of the PRISCUS research consortium allow a better description of consequences of multimorbidity and illustrate at least some new approaches towards prevention, diagnosis, and treatment of patients suffering from multimorbidity. Ongoing projects will test the efficacy of a physical activity program and a new complex intervention to reduce potentially inappropriate medication in the elderly. With this, the research consortium will create some prerequisites for a new health care model for patients with multimorbidity comparable to the Chronic Care Model.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.