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Background
The Federal Ministry of Education and Research of Germany (BMBF) funds a network of university medicines (NUM) to support COVID-19 and pandemic research at national level. The “COVID-19 Data Exchange Platform” (CODEX) as part of NUM establishes a harmonised infrastructure that supports research use of COVID-19 datasets. The broad consent (BC) of the Medical Informatics Initiative (MII) is agreed by all German federal states and forms the legal base for data processing. All 34 participating university hospitals (NUM sites) work upon a harmonised infrastructural as well as legal basis for their data protection-compliant collection and transfer of their research dataset to the central CODEX platform. Each NUM site ensures that the exchanged consent information conforms to the already-balloted HL7 FHIR consent profiles and the interoperability concept of the MII Task Force “Consent Implementation” (TFCI). The Independent Trusted Third-Party (TTP) of the University Medicine Greifswald supports data protection-compliant data processing and provides the consent management solutions gICS.
Methods
Based on a stakeholder dialogue a required set of FHIR-functionalities was identified and technically specified supported by official FHIR experts. Next, a “TTP-FHIR Gateway” for the HL7 FHIR-compliant exchange of consent information using gICS was implemented. A last step included external integration tests and the development of a pre-configured consent template for the BC for the NUM sites.
Results
A FHIR-compliant gICS-release and a corresponding consent template for the BC were provided to all NUM sites in June 2021. All FHIR functionalities comply with the already-balloted FHIR consent profiles of the HL7 Working Group Consent Management. The consent template simplifies the technical BC rollout and the corresponding implementation of the TFCI interoperability concept at the NUM sites.
Conclusions
This article shows that a HL7 FHIR-compliant and interoperable nationwide exchange of consent information could be built using of the consent management software gICS and the provided TTP-FHIR Gateway. The initial functional scope of the solution covers the requirements identified in the NUM-CODEX setting. The semantic correctness of these functionalities was validated by project-partners from the Ludwig-Maximilian University in Munich. The production rollout of the solution package to all NUM sites has started successfully.
Dementia is a leading cause of disability and dependency in older people worldwide. As the number of people affected increases, so does the need for innovative care models. Dementia care management (DCM) is an empirically validated approach for improving the care and quality of life for people with dementia (PwD) and caregivers. The aim of this study is to investigate the influencing factors and critical pathways for the implementation of a regionally adapted DCM standard in the existing primary care structures in the German region of Siegen-Wittgenstein (SW). Utilizing participatory research methods, five local health care experts as co-researchers conducted N = 13 semi-structured interviews with 22 local professionals and one caregiver as peer reviewers. Data collection and analysis were based on the Consolidated Framework for Implementation Research (CFIR). Our results show that among the most mentioned influencing factors, three CFIR constructs can be identified as both barriers and facilitators: Patients’ needs and resources, Relative advantage, and Cosmopolitanism. The insufficient involvement of relevant stakeholders is the major barrier and the comprehensive consideration of patient needs through dementia care managers is the strongest facilitating factor. The study underlines the vital role of barrier analysis in site-specific DCM implementation.
Background
A redistribution of tasks between specialized nurses and primary care physicians, i.e., models of advanced nursing practice, has the potential to improve the treatment and care of the growing number of people with dementia (PwD). Especially in rural areas with limited access to primary care physicians and specialists, these models might improve PwD’s quality of life and well-being. However, such care models are not available in Germany in regular healthcare. This study examines the acceptance, safety, efficacy, and health economic efficiency of an advanced nursing practice model for PwD in the primary care setting in Germany.
Methods
InDePendent is a two-arm, multi-center, cluster-randomized controlled intervention study. Inclusion criteria are age ≥70 years, cognitively impaired (DemTect ≤8) or formally diagnosed with dementia, and living in the own home. Patients will be recruited by general practitioners or specialists. Randomization is carried out at the physicians’ level in a ratio of 1:2 (intervention vs. waiting-control group). After study inclusion, all participants will receive a baseline assessment and a follow-up assessment after 6 months. Patients of the intervention group will receive advanced dementia care management for 6 months, carried out by specialized nurses, who will conduct certain tasks, usually carried out by primary care physicians. This includes a standardized assessment of the patients’ unmet needs, the generation and implementation of an individualized care plan to address the patients’ needs in close coordination with the GP. PwD in the waiting-control group will receive routine care for 6 months and subsequently become part of the intervention group. The primary outcome is the number of unmet needs after 6 months measured by the Camberwell Assessment of Need for the Elderly (CANE). The primary analysis after 6 months is carried out using multilevel models and will be based on the intention-to-treat principle. Secondary outcomes are quality of life, caregiver burden, acceptance, and cost-effectiveness. In total, n=465 participants are needed to assess significant differences in the number of unmet needs between the intervention and control groups.
Discussion
The study will provide evidence about the acceptance, efficacy, and cost-effectiveness of an innovative interprofessional concept based on advanced nursing care. Results will contribute to the implementation of such models in the German healthcare system. The goal is to improve the current treatment and care situation for PwD and their caregivers and to expand nursing roles.
Background: Alcohol consumption accounts for a high burden of disease. The general population of West Pomerania has been characterized as a population at risk with a high prevalence of behavioural risk factors such as alcohol risk drinking. This is reflected by the high proportion of patients being admitted to general hospitals due to alcohol-attributable diseases. The aims of the present dissertation were (a) to analyze dose-response relations between volume of alcohol drinking and the risk of diseases with different alcohol-attributable fractions (AAF) in general hospital inpatients (study 1); (b) to assess motivation to change drinking behaviour and motivation to seek help for alcohol problems during their hospital stay as well as changes in motivation to change drinking behaviour, motivation to seek help and changes in daily alcohol consumption across time according to diseases with different AAFs (study 2); and (c) to investigate the association of fatty liver disease (FLD) with blood pressure and hypertension in a general population sample and to test for the specific contribution of alcohol consumption to this association (study 3). Methods: For studies 1 and 2, data from 'Early Intervention at General Hospitals', a randomized controlled trial to test the effectiveness of brief intervention for alcohol problem drinking in general hospitals, were used. Study 1 comprised data from 846 inpatients, study 2 comprised data from 294 inpatients aged 18 to 64 years with alcohol problem drinking and alcohol-attributable diseases from four general hospitals in West Pomerania. Hospital diagnoses were classified according to their AAF: (1) diseases wholly attributable to alcohol consumption by definition (AAF=1), (2) diseases partially attributable to alcohol consumption (AAF<1), and (3) diseases with no relation to alcohol consumption or where alcohol consumption has been found to be a protective factor (AAF=0). Study 3 encompassed data from the 'Study of Health in Pomerania', a general population sample of 3191 adults aged 20-79 years. FLD was defined using ultrasound in combination with increased serum alanine aminotransferase levels. Results: Analyses showed that 46.8% of the general hospital inpatients had a disease attributable to alcohol consumption. There was a dose-response relationship between volume of alcohol drinking and the risk of diseases with different AAFs. Inpatients consuming >120 g and inpatients consuming 61-120 g of pure alcohol per day revealed significantly higher odds for diseases with AAF=1 compared to inpatients consuming 31-60 g of pure alcohol per day with odds ratios (OR) of 6.3 (95% CI 3.6-11.3) and 2.9 (95% CI 1.6-5.1), respectively. Regarding diseases with AAF<1, inpatients consuming >120 g of pure alcohol per day had significantly higher odds compared to inpatients consuming 31-60 g of pure alcohol per day (OR 2.0, CI 1.2-3.4). Analyses on motivation to change drinking behaviour and on motivation to seek help at hospitalization revealed that motivation to change drinking behaviour was higher among inpatients with alcohol-attributable diseases than among inpatients without alcohol-attributable diseases (p<.001). Among inpatients with AAF=1, motivation to seek help was higher than among inpatients with AAF<1 and AAF=0 (p<.001). While motivation to change drinking behaviour remained stable within one year after hospitalization in all three AAF groups, motivation to seek help decreased in this time period. The volume of alcohol consumed decreased in all three AAF groups within one year after hospitalization. Data from the general population study revealed that FLD was associated with blood pressure and hypertension at baseline and at five-year examination follow-up. For example, the chance of hypertension at both time points was threefold higher in individuals with FLD (OR 2.8, CI 1.3-6.2; OR 3.1, CI 1.7-5.8, respectively) compared to individuals without FLD. Analyses further revealed that the association of FLD with blood pressure and hypertension was independent of alcohol consumption. Conclusion: The results of the present dissertation provide relevant implications for public health. In view of the high proportion of general hospital inpatients with alcohol-attributable diseases, a screening procedure for problem drinking is needed. Furthermore, appropriate interventions considering the inpatient’s motivational level have to be implemented. The concept of AAFs to classify disease conditions according to their causal relationship with alcohol consumption might be a tool to detect inpatients with problem drinking. The results regarding FLD and its association with blood pressure and hypertension demonstrate that it is important to pay attention to alcohol-attributable diseases in the general population and that alcohol-attributable diseases are associated with subsequent serious sequelae. The results of the present work further indicate that the concept to distinguish between alcoholic and non-alcoholic origin of FLD might be obsolete and should be replaced by a concept that regards FLD as a multifactorial disease condition.
Previous studies on the antimicrobial activity of cold atmospheric pressure argon plasma showed varying effects against mecA<sup>+</sup> or mecA<sup>-</sup>Staphylococcus aureus strains. This observation may have important clinical and epidemiological implications. Here, the antibacterial activity of argon plasma was investigated against 78 genetically different S. aureus strains, stratified by mecA, luk-P, agr1-4, or the cell wall capsule polysaccharide types 5 and 8. kINPen09® served as the plasma source for all experiments. On agar plates, mecA<sup>+</sup>luk-P<sup>-</sup>S. aureus strains showed a decreased susceptibility against plasma compared to other S. aureus strains. This study underlines the high complexity of microbial defence against antimicrobial treatment and confirms a previously reported strain-dependent susceptibility of S. aureus to plasma treatment.
Introduction: Hearing and vision loss are highly prevalent in elderly adults, and thus frequently occur in conjunction with cognitive impairments. Studies have shown that hearing impairment is associated with a higher risk of dementia. However, evidence concerning the association between vision loss and dementia, as well as the co-occurrence of vision and hearing loss and dementia, has been inconclusive.
Objectives: To assess the association between: (i) either hearing or vision loss and the risk of dementia, as well as between; and (ii) the combination of both sensory impairments and the risk of dementia.
Methods: This case-control study was based on a 5-year data set that included patients aged 65 years and older who had initially been diagnosed with dementia diseases by one of 1,203 general practitioners in Germany between January 2013 and December 2017. In total, 61,354 identified dementia cases were matched to non-dementia controls, resulting in a sample size of 122,708 individuals. Hearing loss and vision loss were identified using the ICD-10 diagnoses documented in the general practitioners’ files prior to the initial dementia diagnosis. Multivariate logistic regression models were fitted to evaluate the associations between visual and/or hearing impairment and the risk of dementia and controlled for sociodemographic and clinical variables.
Results: Hearing impairment was documented in 11.2% of patients with a dementia diagnosis and 9.5% of patients without such a diagnosis. Some form of vision impairment was documented in 28.4% of patients diagnosed with dementia and 28.8% of controls. Visual impairment was not significantly associated with dementia (OR = 0.97, CI = 95% 0.97–1.02, p = 0.219). However, patients with hearing impairment were at a significantly higher risk of developing dementia (OR = 1.26, CI = 95% 1.15–1.38, p < 0.001), a finding that very likely led to the observed significant association of the combination of both visual and hearing impairments and the risk of dementia (OR = 1.14, CI = 95% 1.04–1.24, p = 0.005).
Discussion: This analysis adds important evidence that contributes to the limited body of knowledge about the association between hearing and/or vision loss and dementia. It further demonstrates that, of the two, only hearing impairment affects patients’ cognition and thus contributes to dementia risk.
The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.
Background: Fatigue, dyspnea, and lack of energy and concentration are commonly interpreted as indicative of symptomatic anemia and may thus play a role in diagnostic and therapeutic decisions. Objective: To investigate the association between symptoms commonly attributed to anemia and the actual presence of anemia. Methods: Data from two independent cohorts of the Study of Health in Pomerania (SHIP) were analyzed. Interview data, laboratory data, and physical examination were individually linked with claims data from the Association of Statutory Health Insurance Physicians. A complete case analysis using logistic regression models was performed to evaluate the association of anemia with symptoms commonly attributed to anemia. The models were adjusted for confounders such as depression, medication, insomnia, and other medical conditions. Results: A total of 5979 participants (53% female, median age 55) were included in the analysis. Of those, 30% reported fatigue, 16% reported lack of energy, 16% reported lack of concentration, and 29% reported dyspnea and/or weakness. Anemia was prevalent in about 6% (379). The symptoms were more prevalent in participants with anemia. However, participants with anemia were older and had a poorer health status. There was no association in multivariate logistic regression models between the symptoms fatigue, lack of concentration, dyspnea, and/or weakness and anemia. Anemia was associated (OR: 1.45; 95% CI: 1.13–1.86) with lack of energy in the multivariate analysis. Other factors such as depression, insomnia, and medication were more strongly associated with the symptoms. Conclusion: The clinical symptoms commonly attributed to anemia are unspecific and highly prevalent both in non-anemic and anemic persons. Even in the presence of anemia, other diagnoses should be considered as causes such as depression, heart failure, asthma, and COPD, which are more closely associated with the symptoms. Further diagnostic research is warranted to explore the association of symptoms in different subgroups and settings in order to help clinical decision making.
Background
Long periods of uninterrupted sitting, i.e., sedentary bouts, and their relationship with adverse health outcomes have moved into focus of public health recommendations. However, evidence on associations between sedentary bouts and adiposity markers is limited. Our aim was to investigate associations of the daily number of sedentary bouts with waist circumference (WC) and body mass index (BMI) in a sample of middle-aged to older adults.
Methods
In this cross-sectional study, data were collected from three different studies that took place in the area of Greifswald, Northern Germany, between 2012 and 2018. In total, 460 adults from the general population aged 40 to 75 years and without known cardiovascular disease wore tri-axial accelerometers (ActiGraph Model GT3X+, Pensacola, FL) on the hip for seven consecutive days. A wear time of ≥ 10 h on ≥ 4 days was required for analyses. WC (cm) and BMI (kg m− 2) were measured in a standardized way. Separate multilevel mixed-effects linear regression analyses were used to investigate associations of sedentary bouts (1 to 10 min, >10 to 30 min, and >30 min) with WC and BMI. Models were adjusted for potential confounders including sex, age, school education, employment, current smoking, season of data collection, and composition of accelerometer-based time use.
Results
Participants (66% females) were on average 57.1 (standard deviation, SD 8.5) years old and 36% had a school education >10 years. The mean number of sedentary bouts per day was 95.1 (SD 25.0) for 1-to-10-minute bouts, 13.3 (SD 3.4) for >10-to-30-minute bouts and 3.5 (SD 1.9) for >30-minute bouts. Mean WC was 91.1 cm (SD 12.3) and mean BMI was 26.9 kg m− 2 (SD 3.8). The daily number of 1-to-10-minute bouts was inversely associated with BMI (b = -0.027; p = 0.047) and the daily number of >30-minute bouts was positively associated with WC (b = 0.330; p = 0.001). All other associations were not statistically significant.
Conclusion
The findings provide some evidence on favourable associations of short sedentary bouts as well as unfavourable associations of long sedentary bouts with adiposity markers. Our results may contribute to a growing body of literature that can help to define public health recommendations for interrupting prolonged sedentary periods.
Trial registration
Study 1: German Clinical Trials Register (DRKS00010996); study 2: ClinicalTrials.gov (NCT02990039); study 3: ClinicalTrials.gov (NCT03539237).
Liver dysfunctions are commonly associated with diabetes and mortality in the general
population. However, previous studies lack to define these disorders with hepatic markers from
MRI, which have been shown to be more accurate and sensitive than hepatic ultrasound and
laboratory markers. Further, previous studies defining different categories of prediabetes by oral
glucose tolerance states revealed controversial findings. Hence, this dissertation contributed to
understand the associations of liver dysfunctions with glucose intolerance states and all-cause
mortality in the general population.
In the first part of the dissertation, the associations of MRI-related hepatic steatosis and hepatic
iron overload with prediabetes were investigated. Prediabetes was categorized into IFG, IGT,
(alone or in combination) or previously unknown type 2 diabetes mellitus using OGGT data, as
suggested by the ADA. For analyses, we included 1632 subjects with MRI who participated in
an OGTT and reported no type 2 diabetes mellitus. We found that hepatic steatosis was
positively associated with continuous markers of glucose metabolism. Similarly, subjects with
hepatic steatosis as defined by MRI had a higher relative risk ratio to be in the prediabetes
groups (i-IFG, i-IGT and IFG + IGT) or having undiagnosed diabetes than individuals without
this condition. The observed associations were more obvious for MRI-derived hepatic steatosis
compared to ultrasound. In comparison to hepatic steatosis, we found that MRI-assessed hepatic
iron overload was positively associated only with both 2-hour plasma glucose and the combined
IFG + IGT category. There were no significant associations between hepatic iron overload and
other glucose tolerance states or biomarkers of glucose metabolism, regardless of possible
confounding factors.
In the second part, the associations of liver volume and other markers of hepatic steatosis with
all-cause mortality in the general population were investigated. We included 2769 middle-aged
German subjects with a median follow-up of 8.9 years (23,898 person-years). Serum liver
enzymes and FIB-4 score were used as quantitative markers, while MRI measurements of liver
fat content and total liver volume included as qualitative markers of hepatic steatosis. Compared
to other markers of hepatic steatosis, larger liver volumes were significantly associated with a
nearly three-fold increase in the long-term risk of all-cause mortality. Furthermore, this
association was consistent across all subgroups considered (men vs. women; presence or absence
of metabolic syndrome or type 2 diabetes at baseline). A positive association between FIB-4
score and all-cause mortality was found both in the entire cohort and in women. Likewise,
positive associations of higher serum AST and GGT levels with all-cause mortality were found
in the entire cohort and in men.
To conclude, this dissertation acknowledges the fact that prevention and early intervention of
liver dysfunction has major impact to reduce the burden of public health problems. Thus, our
findings suggest that hepatic markers contributes to an increased risk of prediabetes and all-cause
mortality, which might be helpful to identify high risk groups who need closer attention with
respect to prevention of liver disorders and diabetes.
Background: The aim of our study was to investigate associations of spleen volume with blood count markers and lipid profile in the general population.
Materials & methods: Cross-sectional data from 1,106 individuals aged 30–90 years from the population-based Study of Health in Pomerania (SHIP-START-2) were analyzed. Blood count markers included red blood cell (RBC) counts, hemoglobin, platelet count, and white blood cell (WBC) counts. Lipid profile included total-cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) as well as triglycerides. Linear regression models adjusted for age, sex, body height, and weight were used to associate standardized spleen volume with blood counts and lipid profile markers.
Results: Spleen volume was positively associated with RBC (β = 0.05; 95% confidence interval [CI] = 0.03 to 0.08) and hemoglobin (β = 0.05; 95% CI = 0.01 to 0.09) but inversely with platelet count (β = −16.3; 95% CI = –20.5 to −12.1) and WBC (β = −0.25; 95% CI = −0.37 to −0.14). Furthermore, spleen volume showed inverse associations with total cholesterol (β = −0.17; 95% CI = −0.24 to −0.09), HDL-C (β = −0.08; 95% CI = −0.10 to −0.05), and LDL-C (β = −0.12; 95% CI = −0.17 to −0.06). There was no significant association of spleen volume with triglycerides.
Conclusion: Our study showed that the spleen volume is associated with markers of the blood count and lipid profile in the general population.
Background
Vulnerable groups, e.g. persons with mental illness, neurological deficits or dementia, are often excluded as participants from research projects because obtaining informed consent can be difficult and tedious. This may have the consequence that vulnerable groups benefit less from medical progress. Vulnerable persons are often supported by a legal guardian in one or more demands of their daily life. We examined the attitudes of legal guardians and legally supervised persons towards medical research and the conditions and motivations to participate in studies.
Methods
We conducted a cross-sectional study with standardized surveys of legal guardians and legally supervised persons. Two separate questionnaires were developed for the legal guardians and the supervised persons to asses previous experiences with research projects and the reasons for participation or non-participation. The legal guardians were recruited through various guardianship organizations. The supervised persons were recruited through their legal guardian and from a previous study among psychiatric patients. The data were analysed descriptively.
Results
Alltogether, 82 legal guardians and 20 legally supervised persons could be recruited. Thereof 13 legal guardians (15.6%) and 13 legally supervised persons (65.0%) had previous experience with research projects. The majority of the guardians with experience in research projects had consented the participation of their supervised persons (n = 12 guardians, 60.0%; in total n = 16 approvals). The possible burden on the participating person was given as the most frequent reason not to participate both by the guardians (n = 44, 54.4%) and by the supervised persons (n = 3, 30.0%). The most frequent motivation to provide consent to participate in a research study was the desire to help other patients by gaining new scientific knowledge (guardians: n = 125, 78.1%; supervised persons: n = 10, 66.6%).
Conclusions
Overall, an open attitude towards medical research can be observed both among legal guardians and supervised persons. Perceived risks and no sense recognized in the study are reasons for not participating in medical research projects.
Frontotemporal lobar degeneration (FTLD) is likely to be the second-most common cause of dementia in individuals under 65 years of age. Pathognomonic changes in personality, behavior and motivation are known to lead to high caregiver stress and burden, with little support being available. The aim of this work is to present the current state of knowledge on the characteristics, challenges and unmet needs of caregivers as well as on possible interventions.
Two scoping reviews on caregiver burden using the PRISMA checklist for scoping reviews were conducted using PubMed, Web of Science and ScienceDirect in April 2017 and November 2019, respectively. A total of 107 articles were considered eligible and were analyzed qualitatively and summarized.
Our results show that caregivers of patients with FTLD are often female, spouses of the PwD, younger in age, have underage children and provide care at home. Behavioral and motivational disturbances in the PwD are perceived to be the most burdensome aspects of caregiving. Those caring for an individual with the bvFTD subtype thus report higher levels of burden than caregivers of an individual with a form of PPA. With rising dementia severity, caregivers report higher levels of burden. Many caregivers experience a decline in their own physical and mental health as well as a significant financial burden resulting from care duties. The deterioration of the relationship between the PwD and their caregivers is a main burdensome aspect. Only few interventions were conducted so far, and none of those that were identified were designed as an RCT. The most efficacious interventions were those aimed directly at caregivers, whereas interventions aiming at the amelioration of symptoms in the PwD showed little effect.
Further research should reproduce and validate efficacious interventions and establish new interventional approaches. Another focus should be set on the situation of underage children of individuals with FTLD and relatives of a person with hereditary FTD. More research from non-Western countries is needed in order to identify culture-specific factors of caregiver burden. Along those lines, support structures for FTLD caregivers should be assessed on a local basis and extended accordingly. So far, no study has assessed the relationship between caregiver burden and possible consequences for the quality of care provided to the PwD in FTLD specifically. Awareness both in the wider population and among healthcare professionals is an urgent need for the future since FTLD is often misdiagnosed, leading to a delay in obtaining the correct diagnosis and access to suitable support.
The impact of the COVID-19 pandemic on social-emotional developmental risks (SE-DR) of preschool children is largely unknown. Therefore, the aim of this prospective longitudinal dynamic cohort study was to assess changes in preschoolers’ SE-DR from before the pandemic to after the first COVID-19 wave. SE-DR were assessed annually with the instrument “Dortmund Developmental Screening for Preschools” (DESK). Longitudinal DESK data from 3- to 4-year-old children who participated both in survey wave (SW) three (DESK-SW3, 2019) and SW four (DESK-SW4, 2020) from August 1 to November 30 were used, respectively. Additionally, data from previous pre-pandemic SW were analyzed to contextualize the observed changes (SW1: 2017; SW2: 2018). A total of N = 786 children were included in the analysis. In the pre-pandemic DESK-SW3, the proportion of children with SE-DR was 18.2%, whereas in DESK-SW4 after the first COVID-19 wave, the proportion decreased to 12.4% (p = 0.001). Thus, the prevalence rate ratio (PRR) was 0.68. Compared to data from previous SW (SW1-SW2: PRR = 0.88; SW2-SW3: PRR = 0.82), this result represents a notable improvement. However, only short-term effects were described, and the study region had one of the highest preschool return rates in Germany. Further studies are needed to examine long-term effects of the pandemic on preschoolers’ SE-DR.
Abstract
The increasing global prevalence of dementia demands concrete actions that are aimed strategically at optimizing processes that drive clinical innovation. The first step in this direction requires outlining hurdles in the transition from research to practice. The different parties needed to support translational processes have communication mismatches; methodological gaps hamper evidence‐based decision‐making; and data are insufficient to provide reliable estimates of long‐term health benefits and costs in decisional models. Pilot projects are tackling some of these gaps, but appropriate methods often still need to be devised or adapted to the dementia field. A consistent implementation perspective along the whole translational continuum, explicitly defined and shared among the relevant stakeholders, should overcome the “research‐versus‐adoption” dichotomy, and tackle the implementation cliff early on. Concrete next steps may consist of providing tools that support the effective participation of heterogeneous stakeholders and agreeing on a definition of clinical significance that facilitates the selection of proper outcome measures.
This dynamic cohort was established to evaluate the targeted individual promotion of children affected by developmental risks as part of the German federal state law for child day-care and preschools in Mecklenburg-Western Pomerania. The project has been conducted in preschools in regions with a low socio-economic profile since 2011. Since 2017, the revision of the standardized Dortmund Developmental Screening for Preschools (DESK 3–6 R) has been applied. Developmental risks of 3 to 6-year-old children in the domains of motor, linguistic, cognitive and social competencies are monitored. The cohort is followed up annually. In 2020, n = 7,678 children from n = 152 preschools participated. At the baseline (2017), n = 8,439 children participated. Due to the defined age range of this screening, 3,000 to 4,000 5-6-year-old children leave the cohort annually. Simultaneously, an approximately equal number of 3-year-old children enters the cohort per survey wave. N = 702 children participated in all 4 survey waves. On the basis of DESK 3–6 R scores available from survey waves 2017 to 2019 it is possible to compute expected values for the survey wave 2020 and to compare those with the measured values to evaluate the effects of the COVID-19 pandemic (i.e. parental home care due to restrictions related to COVID-19).
Mendelian randomization (MR) is a framework for assessing causal inference using cross-sectional data in combination with genetic information. This paper summarizes statistical methods commonly applied and strait forward to use for conducting MR analyses including those taking advantage of the rich dataset of SNP-trait associations that were revealed in the last decade through large-scale genome-wide association studies. Using these data, powerful MR studies are possible. However, the causal estimate may be biased in case the assumptions of MR are violated. The source and the type of this bias are described while providing a summary of the mathematical formulas that should help estimating the magnitude and direction of the potential bias depending on the specific research setting. Finally, methods for relaxing the assumptions and for conducting sensitivity analyses are discussed. Future researches in the field of MR include the assessment of non-linear causal effects, and automatic detection of invalid instruments.
Mendelian randomization (MR) is a framework for assessing causal inference using cross-sectional data in combination with genetic information. This paper summarizes statistical methods commonly applied and strait forward to use for conducting MR analyses including those taking advantage of the rich dataset of SNP-trait associations that were revealed in the last decade through large-scale genome-wide association studies. Using these data, powerful MR studies are possible. However, the causal estimate may be biased in case the assumptions of MR are violated. The source and the type of this bias are described while providing a summary of the mathematical formulas that should help estimating the magnitude and direction of the potential bias depending on the specific research setting. Finally, methods for relaxing the assumptions and for conducting sensitivity analyses are discussed. Future researches in the field of MR include the assessment of non-linear causal effects, and automatic detection of invalid instruments.
Background
The care of palliative patients takes place as non-specialized and specialized care, in outpatient and inpatient settings. However, palliative care is largely provided as General Outpatient Palliative Care (GOPC). This study aimed to investigate whether the survival curves of GOPC patients differed from those of the more intensive palliative care modalities and whether GOPC palliative care was appropriate in terms of timing.
Methods
The study is based on claims data from a large statutory health insurance. The analysis included 4177 patients who received palliative care starting in 2015 and who were fully insured 1 year before and 1 year after palliative care or until death. The probability of survival was observed for 12 months. Patients were classified into group A, which consisted of patients who received palliative care only with GOPC, and group B including patients who received inpatient or specialized outpatient palliative care. Group A was further divided into two subgroups. Patients who received GOPC on only 1 day were assigned to subgroup A1, and patients who received GOPC on two or more days were assigned to subgroup A2. The survival analysis was carried out using Kaplan-Meier curves. The median survival times were compared with the log-rank test.
Results
The survival curves differed between groups A and B, except in the first quartile of the survival distribution. The median survival was significantly longer in group A (137 days, n = 2763) than in group B (47 days, n = 1424, p < 0.0001) and shorter in group A1 (35 days, n = 986) than in group A2 (217 days, n = 1767, p < 0.0001). The survival rate during the 12-month follow-up was higher in group A (42%) than in group B (11%) and lower in group A1 (38%) than in group A2 (44%).
Conclusions
The results of the analysis revealed that patients who received the first palliative care shortly before death suspected insufficient care, especially patients who received GOPC for only 1 day and no further palliative care until death or 12-month follow-up. Palliative care should start as early as necessary and be continuous until the end of life.
CFTR encodes for a chloride and bicarbonate channel expressed at the apical membrane of polarized epithelial cells. Transepithelial sodium transport mediated by the amiloride-sensitive sodium channel ENaC is thought to contribute to the manifestation of CF disease. Thus, ENaC is a therapeutic target in CF and a valid cystic fibrosis modifier gene. We have characterized SCNN1B as a genetic modifier in the three independent patient cohorts of F508del-CFTR homozygotes. We could identify a regulatory element at SCNN1B to the genomic segment rs168748-rs2303153-rs4968000 by fine-mapping (Pbest = 0.0177), consistently observing the risk allele rs2303153-C and the contrasting benign allele rs2303153-G in all three patient cohorts. Furthermore, our results show that expression levels of SCNN1B are associated with rs2303153 genotype in intestinal epithelia (P = 0.003). Our data confirm that the well-established biological role of SCNN1B can be recognized by an association study on informative endophenotypes in the rare disease cystic fibrosis and calls attention to reproducible results in association studies obtained from small, albeit carefully characterized patient populations.
Copattern of depression and alcohol use in medical care patients: cross- sectional study in Germany
(2020)
Objective
To predict depressive symptom severity and presence of major depression along the full alcohol use continuum.
Design
Cross-sectional study.
Setting
Ambulatory practices and general hospitals from three sites in Germany.
Participants
Consecutive patients aged 18–64 years were proactively approached for an anonymous health screening (participation rate=87%, N=12 828). Four continuous alcohol use measures were derived from an expanded Alcohol Use Disorder Identification Test (AUDIT): alcohol consumption in grams per day and occasion, excessive consumption in days per months and the AUDIT sum score. Depressive symptoms were assessed for the worst 2-week period in the last 12 months using the Patient Health Questionnaire (PHQ-8). Negative binomial and logistic regression analyses were used to predict depressive symptom severity (PHQ-8 sum score) and presence of major depression (PHQ-8 sum score≥10) by the alcohol use measures.
Results
Analyses revealed that depressive symptom severity and presence of major depression were significantly predicted by all alcohol use measures after controlling for sociodemographics and health behaviours (p<0.05). The relationships were curvilinear: lowest depressive symptom severity and odds of major depression were found for alcohol consumptions of 1.1 g/day, 10.5 g/occasion, 1 excessive consumption day/month, and those with an AUDIT score of 2. Higher depressive symptom severity and odds of major depression were found for both abstinence from and higher levels of alcohol consumption. Interaction analyses revealed steeper risk increases in women and younger individuals for most alcohol use measures.
Conclusion
Findings indicate that alcohol use and depression in medical care patients are associated in a curvilinear manner and that moderation by gender and age is present.
Background
Over the course of the COVID-19 pandemic, previous studies have shown that the physical as well as the mental health of children and adolescents significantly deteriorated. Future anxiety caused by the COVID-19 pandemic and its associations with quality of life has not previously been examined in school children.
Methods
As part of a cross-sectional web-based survey at schools in Mecklenburg-Western Pomerania, Germany, two years after the outbreak of the pandemic, school children were asked about COVID-19-related future anxiety using the German epidemic-related Dark Future Scale for children (eDFS-K). Health-related quality of life (HRQoL) was assessed using the self-reported KIDSCREEN-10. The eDFS-K was psychometrically analyzed (internal consistency and confirmatory factor analysis) and thereafter examined as a predictor of HRQoL in a general linear regression model.
Results
A total of N = 840 8–18-year-old children and adolescents were included in the analysis. The eDFS-K demonstrated adequate internal consistency reliability (Cronbach's α = 0.77), and the confirmatory factor analysis further supported the one-factor structure of the four-item scale with an acceptable model fit. Over 43% of students were found to have low HRQoL. In addition, 47% of the students sometimes to often reported COVID-19-related fears about the future. Children with COVID-19-related future anxiety had significantly lower HRQoL (B = – 0.94, p < 0.001). Other predictors of lower HRQoL were older age (B = – 0.63, p < 0.001), and female (B = – 3.12, p < 0.001) and diverse (B = – 6.82, p < 0.001) gender.
Conclusion
Two years after the outbreak of the pandemic, school-aged children continue to exhibit low HRQoL, which is further exacerbated in the presence of COVID-19-related future anxiety. Intervention programs with an increased focus on mental health also addressing future anxiety should be provided.
Literature shows that people with a migration background (PwM) with dementia are an especially vulnerable group. Data on the number of PwM with dementia in Germany is scarce meaning the healthcare system faces a challenge of an unknown magnitude. They are mostly not part of the healthcare landscape and lack knowledge about dementia and healthcare services. Healthcare professionals and services do not seem to be culturally sensitive enough and not adequately equipped to take care of PwM with dementia. Therefore, this work focuses on a) estimating the number of PwM with dementia broken down by country of origin and federal state; b) exploring the caregiving experience, barriers of healthcare utilisation and measures to increase utilisation; and c) determining the scope of culturally sensitive information and healthcare services as well as projects on dementia and migration in Germany. A combination of quantitative and qualitative research methods as well as a scoping review are applied to examine the research focus.
Calculations show that an estimated 96,500 PwM have dementia, presumably mostly originating from Poland, Italy, Turkey, Romania, and the Russian Federation. The majority of affected PwM live in North Rhine-Westphalia, Baden-Württemberg, and Bavaria. Family members experience similar challenges and consequences as non-migrants in the care of a person with dementia. PwM lack sufficient knowledge of dementia and information regarding the available healthcare services. These are only two of the reasons why the healthcare system is not utilised. To increase utilisation, services should be culturally sensitive and information easily accessible. In addition, easier navigation and the expansion of existing healthcare structures is needed. The scoping review identified 48 culturally sensitive healthcare and information services and projects for PwM with dementia. The majority are located in North Rhine-Westphalia, Baden-Württemberg, Bavaria, and Hesse, which mirrors the distribution of PwM with dementia in Germany. For the most part, these services offer counselling in different languages. These results confirm that PwM (with dementia) and healthcare professionals need in-depth education on this topic. There should be a focus on the design of information and healthcare services that are tailored in a culturally sensitive way. This dissertation further indicates that culturally sensitive healthcare services, personalised for individual situations on site, should be expanded and also facilitated by not only healthcare professionals and service providers but also by law- and decision-makers. Furthermore, there is a need for cooperation between researchers, healthcare professionals, service providers, healthcare systems, law-makers, and other stakeholders in the field on a national and an international level.
Background: Person-centered care (PCC) requires knowledge about patient preferences. This formative qualitative study aimed to identify (sub)criteria of PCC for the design of a quantitative, choice-based instrument to elicit patient preferences for person-centered dementia care. Method: Interviews were conducted with n = 2 dementia care managers, n = 10 People living with Dementia (PlwD), and n = 3 caregivers (CGs), which followed a semi-structured interview guide including a card game with PCC criteria identified from the literature. Criteria cards were shown to explore the PlwD’s conception. PlwD were asked to rank the cards to identify patient-relevant criteria of PCC. Audios were verbatim-transcribed and analyzed with qualitative content analysis. Card game results were coded on a 10-point-scale, and sums and means for criteria were calculated. Results: Six criteria with two sub-criteria emerged from the analysis; social relationships (indirect contact, direct contact), cognitive training (passive, active), organization of care (decentralized structures and no shared decision making, centralized structures and shared decision making), assistance with daily activities (professional, family member), characteristics of care professionals (empathy, education and work experience) and physical activities (alone, group). Dementia-sensitive wording and balance between comprehensibility vs. completeness of the (sub)criteria emerged as additional themes. Conclusions: Our formative study provides initial data about patient-relevant criteria of PCC to design a quantitative patient preference instrument. Future research may want to consider the balance between (sub)criteria comprehensibility vs. completeness.
Person-centered care (PCC) requires knowledge about patient preferences. An analytic hierarchy process (AHP) is one approach to quantify, weigh and rank patient preferences suitable for People living with Dementia (PlwD), due to simple pairwise comparisons of individual criteria from a complex decision problem. The objective of the present study was to design and pretest a dementia-friendly AHP survey. Methods: Two expert panels consisting of n = 4 Dementia Care Managers and n = 4 physicians to ensure content-validity, and “thinking-aloud” interviews with n = 11 PlwD and n = 3 family caregivers to ensure the face validity of the AHP survey. Following a semi-structured interview guide, PlwD were asked to assess appropriateness and comprehensibility. Data, field notes and partial interview transcripts were analyzed with a constant comparative approach, and feedback was incorporated continuously until PlwD had no further comments or struggles with survey completion. Consistency ratios (CRs) were calculated with Microsoft® Excel and ExpertChoice Comparion®. Results: Three main categories with sub-categories emerged: (1) Content: clear task introduction, (sub)criteria description, criteria homogeneity, (sub)criteria appropriateness, retest questions and sociodemography for heterogeneity; (2) Format: survey structure, pairwise comparison sequence, survey length, graphical design (incl. AHP scale), survey procedure explanation, survey assistance and response perspective; and (3) Layout: easy wording, short sentences and visual aids. Individual CRs ranged from 0.08 to 0.859, and the consolidated CR was 0.37 (0.038). Conclusions: Our formative qualitative study provides initial data for the design of a dementia-friendly AHP survey. Consideration of our findings may contribute to face and content validity in future quantitative preference research in dementia.
The incidence and prevalence of pediatric-onset inflammatory bowel disease (PIBD) are on the rise worldwide. Initial symptoms are often recognized with a delay, which reduces the quality of life and may lead to an increased rate of complications. The aim of this study was to determine the diagnostic delay in PIBD and to identify potential influencing factors. Therefore, data from the German-Austrian patient registry CEDATA-GPGE for children and adolescents with PIBD were analyzed for the period January 2014 to December 2018. There were 456 children identified in the data, thereof 258 children (57%) with Crohn’s disease (CD) and 198 children (43%) with Ulcerative colitis (UC). The median age was 13.3 years (interquartile range (IQR) = 10.9−15.0), and 44% were females. The median diagnostic delay was 4.1 months (IQR = 2.1–7.0) in CD and 2.4 months (IQR = 1.2–5.1) in UC (p = 0.01). UC was associated with earlier diagnosis than CD (p < 0.001). Only a few factors influencing the diagnostic delay have been verified, e.g., abdominal pain at night and if video capsule endoscopy was performed. Diagnostic delay improved over the years in participating centers, but the level of awareness needs to be high even in common symptoms like abdominal pain.
Knowledge on differences in the severity and symptoms of infections with the SARS-CoV-2 Omicron variants BA.2 (Pango lineage B.1.529.2) and BA.5 (Pango lineage B.1.529.5) is still scarce. We investigated epidemiological data available from the public health authorities in Mecklenburg-Western Pomerania, Northeast Germany, between April and July 2022 retrospectively. Comparative analyses revealed significant differences between recorded symptoms of BA.2 and BA.5 infected individuals and found strong correlations of associations between symptoms. In particular, the symptoms ‘chills or sweating’, ‘freeze’ and ‘runny nose’ were more frequently reported in BA.2 infections. In contrast, ‘other clinical symptoms’ appeared more frequently in Omicron infections with BA.5. However, the results obtained in this study provide no evidence that BA.5 has a higher pathogenicity or causes a more severe course of infection than BA.2. To our knowledge, this is the first report on clinical differences between the current Omicron variants BA.2 and BA.5 using public health data. Our study highlights the value of timely investigations of data collected by public health authorities to gather detailed information on the clinical presentation of different SARS-CoV-2 subvariants at an early stage.
Discovery of novel eGFR-associated multiple independent signals using a quasi-adaptive method
(2022)
A decreased estimated glomerular filtration rate (eGFR) leading to chronic kidney disease is a significant public health problem. Kidney function is a heritable trait, and recent application of genome-wide association studies (GWAS) successfully identified multiple eGFR-associated genetic loci. To increase statistical power for detecting independent associations in GWAS loci, we improved our recently developed quasi-adaptive method estimating SNP-specific alpha levels for the conditional analysis, and applied it to the GWAS meta-analysis results of eGFR among 783,978 European-ancestry individuals. Among known eGFR loci, we revealed 19 new independent association signals that were subsequently replicated in the United Kingdom Biobank (n = 408,608). These associations have remained undetected by conditional analysis using the established conservative genome-wide significance level of 5 × 10–8. Functional characterization of known index SNPs and novel independent signals using colocalization of conditional eGFR association results and gene expression in cis across 51 human tissues identified two potentially causal genes across kidney tissues: TSPAN33 and TFDP2, and three candidate genes across other tissues: SLC22A2, LRP2, and CDKN1C. These colocalizations were not identified in the original GWAS. By applying our improved quasi-adaptive method, we successfully identified additional genetic variants associated with eGFR. Considering these signals in colocalization analyses can increase the precision of revealing potentially functional genes of GWAS loci.
Do We Need to Rethink the Epidemiology and Healthcare Utilization of Parkinson's Disease in Germany?
(2018)
Epidemiological aspects of Parkinson's disease (PD), co-occurring diseases and medical healthcare utilization of PD patients are still largely elusive. Based on claims data of 3.7 million statutory insurance members in Germany in 2015 the prevalence and incidence of PD was determined. PD cases had at least one main hospital discharge diagnosis of PD, or one physician diagnosis confirmed by a subsequent or independent diagnosis or by PD medication in 2015. Prevalence of (co-)occurring diseases, mortality, and healthcare measures in PD cases and matched controls were compared. In 2015, 21,714 prevalent PD cases (standardized prevalence: 511.4/100,000 persons) and 3,541 incident PD cases (standardized incidence: 84.1/100,000 persons) were identified. Prevalence of several (co-)occurring diseases/complications, e.g., dementia (PD/controls: 39/13%), depression (45/22%), bladder dysfunction (46/22%), and diabetes (35/31%), as well as mortality (10.7/5.8%) differed between PD cases and controls. The annual healthcare utilization was increased in PD cases compared to controls, e.g., regarding mean ± SD physician contacts (15.2 ± 7.6/12.2 ± 7.3), hospitalizations (1.3 ± 1.8/0.7 ± 1.4), drug prescriptions (overall: 37.7 ± 24.2/21.7 ± 19.6; anti-PD medication: 7.4 ± 7.4/0.1 ± 0.7), assistive/therapeutic devices (47/30%), and therapeutic remedies (57/16%). The standardized prevalence and incidence of PD in Germany as well as mortality in PD may be substantially higher than reported previously. While frequently diagnosed with co-occurring diseases/complications, such as dementia, depression, bladder dysfunction and diabetes, the degree of healthcare utilization shows large variability between PD patients. These findings encourage a rethinking of the epidemiology and healthcare utilization in PD, at least in Germany. Longitudinal studies of insurance claims data should further investigate the individual and epidemiological progression and healthcare demands in PD.
Abstract
Purpose
This study aims to assess the implementation of published research, contraindications, and warnings on the prescription of dual renin‐angiotensin‐hormone system (RAS) blockade in ambulatory care in Germany.
Methods
Cohort study based on health claims data of 6.7 million subjects from 2008 to 2015. Yearly prevalence and incidence for dual RAS blockade with (a) angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers (ACEI + ARB) and (b) aliskiren and ACEI or ARB (aliskiren + ACEI/ARB) were calculated. We assessed prescriber specialty and associations between discontinuing dual RAS blockade with specialist (internal medicine, cardiology, nephrology) visits and hospital discharge in the previous year.
Results
A total of 2 984 517 patients were included (age 51.4 ± SD 18.4 y, 48.5% male). Prescription rates for ACEI + ARB decreased from 0.6% (n = 17 907) to 0.4% (n = 12 237) and for aliskiren + ACEI/ARB from 0.23% (n = 6634) to 0.03% (n = 818). Incident prescriptions decreased from 0.23% (n = 6705) to 0.19% (n = 5055) (ACE + ARB) and from 0.1% (n = 2796) to 0.005% (n = 142) (aliskiren + ACE/ARB); 59% of ACEI + ARB and 48% of aliskiren + ACE/ARB combinations were prescribed only by one physician. Of those, 73% (ACEI + ARB) and 58% (aliskiren + ACE/ARB) were primary care providers (PCPs). Discontinuing dual RAS blockade was associated with specialist care and hospital discharge in the previous year (specialist care: RR 1.4, 95% CI, 1.3‐1.6; hospital visit: RR 1.5, 95% CI, 1.3‐1.6).
Conclusions
Our results suggest a delayed uptake of treatment recommendation for ACEI + ARB and a higher impact of Dear Doctor letters addressing PCPs directly compared with published research, contraindications, and warnings. Targeted continuous medical education, practice software alerts, and stronger involvement of pharmacists might improve the implementation of medication safety recommendations in ambulatory care.
SummaryBackground: According to the literature, ductoscopy is gaining increasing importance in the diagnosis of intraductal anomalies in cases of pathologic nipple discharge. In a multicenter study, the impact of this method was assessed in comparison with that of standard diagnostics. Patients and Methods: Between 09/2006 and 05/2009, a total of 214 patients from 7 German breast centers were included. All patients underwent elective ductoscopy and subsequent ductal excision because of pathologic nipple discharge. Ductoscopy was compared with the following standard diagnostics: breast sonography, mammography, magnetic resonance imaging (MRI), galactography, cytologic nipple swab, and ductal lavage cytology. The histological and imaging results were compared and contrasted to the results obtained from the nipple swab and cytologic assessment. Results: Sonography had the highest (82.9%) sensitivity, followed by MRI (82.5%), galactography (81.3%), ductoscopy (71.2%), lavage cytology (57.8%), mammography (57.1%), and nipple swab (22.8%). Nipple swabs had the highest (85.5%) specificity, followed by lavage cytology (85.2%), ductoscopy (49.4%), galactography (44.4%), mammography (33.3%), sonography (17.9%), and MRI (11.8%). Conclusion: Currently, ductoscopy provides a direct intraoperative visualization of intraductal lesions. Sensitivity and specificity are similar to those of standard diagnostics. The technique supports selective duct excision, in contrast to the unselective technique according to Urban. Therefore, ductoscopy extends the interventional/diagnostic armamentarium.
Background
Numerous wearables are used in a research context to record cardiac activity although their validity and usability has not been fully investigated. The objectives of this study is the cross-model comparison of data quality at different realistic use cases (cognitive and physical tasks). The recording quality is expressed by the ability to accurately detect the QRS complex, the amount of noise in the data, and the quality of RR intervals.
Methods
Five ECG devices (eMotion Faros 360°, Hexoskin Hx1, NeXus-10 MKII, Polar RS800 Multi and SOMNOtouch NIBP) were attached and simultaneously tested in 13 participants. Used test conditions included: measurements during rest, treadmill walking/running, and a cognitive 2-back task. Signal quality was assessed by a new local morphological quality parameter morphSQ which is defined as a weighted peak noise-to-signal ratio on percentage scale. The QRS detection performance was evaluated with eplimited on synchronized data by comparison to ground truth annotations. A modification of the Smith-Waterman algorithm has been used to assess the RR interval quality and to classify incorrect beat annotations. Evaluation metrics includes the positive predictive value, false negative rates, and F1 scores for beat detection performance.
Results
All used devices achieved sufficient signal quality in non-movement conditions. Over all experimental phases, insufficient quality expressed by morphSQ values below 10% was only found in 1.22% of the recorded beats using eMotion Faros 360°whereas the rate was 8.67% with Hexoskin Hx1. Nevertheless, QRS detection performed well across all used devices with positive predictive values between 0.985 and 1.000. False negative rates are ranging between 0.003 and 0.017. eMotion Faros 360°achieved the most stable results among the tested devices with only 5 false positive and 19 misplaced beats across all recordings identified by the Smith-Waterman approach.
Conclusion
Data quality was assessed by two new approaches: analyzing the noise-to-signal ratio using morphSQ, and RR interval quality using Smith-Waterman. Both methods deliver comparable results. However the Smith-Waterman approach allows the direct comparison of RR intervals without the need for signal synchronization whereas morphSQ can be computed locally.
Objectives: An inverse relationship between education and cardiovascular risk has been described, however, the combined association of education, income, and neighborhood socioeconomic status with macrovascular disease is less clear. The aim of this study was to evaluate the association of educational level, equivalent household income and area deprivation with macrovascular disease in Germany.
Methods: Cross-sectional data from two representative German population-based studies, SHIP-TREND (n = 3,731) and KORA-F4 (n = 2,870), were analyzed. Multivariable logistic regression models were applied to estimate odds ratios and 95% confidence intervals for the association between socioeconomic determinants and macrovascular disease (defined as self-reported myocardial infarction or stroke).
Results: The study showed a higher odds of prevalent macrovascular disease in men with low and middle educational level compared to men with high education. Area deprivation and equivalent income were not related to myocardial infarction or stroke in any of the models.
Conclusion: Educational level, but not income or area deprivation, is significantly related to the macrovascular disease in men. Effective prevention of macrovascular disease should therefore start with investing in individual education.
Effectiveness of Varenicline as an Aid to Smoking Cessation in Primary Care: An Observational Study
(2012)
Aims: Although varenicline is commonly prescribed in primary care, information on smoking-related comorbidities and the effectiveness of varenicline in this context in Germany is scarce. This study assessed the efficacy and safety of varenicline in a large sample of patients seeking smoking cessation treatment through their general practitioners. The frequency of comorbidities was also evaluated. Methods: This was a 12-week, prospective, observational, non-comparative phase IV trial conducted in Germany. Abstinence rates at week 12 were evaluated by verbal reporting using the nicotine use inventory. Results: Overall, 1,391 subjects were enrolled; 1,177 received study medication and were evaluated for effectiveness and safety. At the end of the study, 71.1% (95% confidence interval 68.5–73.7) of subjects were abstinent. There were a total of 205 all-causality adverse events; 2.2% were classified as serious or severe. There were no fatal adverse events. At inclusion, 66.7% of participants had at least 1 concurrent comorbidity, with chronic obstructive pulmonary disease (35.5%), hypertension (29.6%) and depression (10.4%) being the most commonly reported. Conclusion: These real-world data indicate that varenicline is an effective and well-tolerated smoking cessation treatment when used in the primary care setting including patients with smoking-related comorbidities.
The Apolipoprotein E (APOE) gene polymorphism (rs429358 and rs7412) shows a well-established association with lipid profiles, but its effect on cardiovascular disease is still conflicting. Therefore, we examined the association of different APOE alleles with common carotid artery intima-media thickness (CCA-IMT), carotid plaques, incident myocardial infarction (MI) and stroke. We analyzed data from 3327 participants aged 20–79 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 14.5 years. Linear, logistic, and Cox-regression models were used to assess the associations of the APOE polymorphism with CCA-IMT, carotid plaques, incident MI and stroke, respectively. In our study, the APOE E2 allele was associated with lower CCA-IMT at baseline compared to E3 homozygotes (β: − 0.02 [95% CI − 0.04, − 0.004]). Over the follow-up, 244 MI events and 218 stroke events were observed. APOE E2 and E4 allele were not associated with incident MI (E2 HR: 1.06 [95% CI 0.68, 1.66]; E4 HR: 1.03 [95% CI 0.73, 1.45]) and incident stroke (E2 HR: 0.79 [95% CI 0.48, 1.30]; E4 HR: 0.96 [95% CI 0.66, 1.38]) in any of the models adjusting for potential confounders. However, the positive association between CCA-IMT and incident MI was more pronounced in E2 carriers than E3 homozygotes. Thus, our study suggests that while APOE E2 allele may predispose individuals to lower CCA-IMT, E2 carriers may be more prone to MI than E3 homozygotes as the CCA-IMT increases. APOE E4 allele had no effect on CCA-IMT, plaques, MI or stroke.
Epidemiological data reveal that there is a need for prevention measures specifically targeted at children with low SES. In the German federal state Mecklenburg-Western Pomerania preschools in socially deprived regions can apply for additional funds to support children with developmental risks. Mandatory criteria for obtaining these funds involve an annual assessment of all children using the “Dortmunder Developmental Screening for Preschools (DESK 3–6 R).” This instrument can detect and monitor developmental risks in the domains fine motor skills, gross motor skills, language, cognition, and social development. In this study, we examine the domain “Attention and concentration,” which is included for the 5 to 6-year-old age group, using data from two consecutive survey waves (sw). Research questions: (1) Does the prevalence rate ratio (PRR) improve over time? (2) Is the rate of improvements (developmental risk at sw1, no developmental risk at sw2) higher than the rate of deteriorations (no developmental risk at sw1, developmental risk at sw2)? Prospective cohort analysis (n = 940). The prevalence rate of a developmental risk in this DESK domain decreases over time (PRR = 0.78; p = 0.019). The ratio of the rate of improvements is 8.47 times higher than the rate of deteriorations. The results provide evidence of the effectiveness of targeted intervention measures in preschools focusing on skills that improve attention and concentration. This is significant considering the small-time interval and the categorization method of DESK scores. Nevertheless, over the same time period, the DESK results of some children deteriorated. Therefore, preschools also have to be aware that it is natural for some children to show modest declines in their skills over time. German Clinical Trials Register, ID: DRKS00015134, Registered on 29 October 2018, retrospectively registered.
Objective
Whole-body MRI (wb-MRI) is increasingly used in research and screening but little is known about the effects of incidental findings (IFs) on health service utilisation and costs. Such effects are particularly critical in an observational study. Our principal research question was therefore how participation in a wb-MRI examination with its resemblance to a population-based health screening is associated with outpatient service costs.
Design
Prospective cohort study.
Setting
General population Mecklenburg-Vorpommern, Germany.
Participants
Analyses included 5019 participants of the Study of Health in Pomerania with statutory health insurance data. 2969 took part in a wb-MRI examination in addition to a clinical examination programme that was administered to all participants. MRI non-participants served as a quasi-experimental control group with propensity score weighting to account for baseline differences.Primary and secondary outcome measuresOutpatient costs (total healthcare usage, primary care, specialist care, laboratory tests, imaging) during 24 months after the examination were retrieved from claims data. Two-part models were used to compute treatment effects.
Results
In total, 1366 potentially relevant IFs were disclosed to 948 MRI participants (32% of all participants); most concerned masses and lesions (769 participants, 81%). Costs for outpatient care during the 2-year observation period amounted to an average of €2547 (95% CI 2424 to 2671) for MRI non-participants and to €2839 (95% CI 2741 to 2936) for MRI participants, indicating an increase of €295 (95% CI 134 to 456) per participant which corresponds to 11.6% (95% CI 5.2% to 17.9%). The cost increase was sustained rather than being a short-term spike. Imaging and specialist care related costs were the main contributors to the increase in costs.
Conclusions
Communicated findings from population-based wb-MRI substantially impacted health service utilisation and costs. This introduced bias into the natural course of healthcare utilisation and should be taken care for in any longitudinal analyses.
Background: Cardiovascular diseases are the leading cause of death worldwide. Subclinical alterations of the cardiovascular system, such as increased exercise blood pressure or an endothelial dysfunction confer a higher risk of manifest cardiovascular diseases and incident events. Detecting associations between circulating markers of the endocrine-metabolic system and the subclinical cardiovascular phenotypes could be useful to better understand cardiovascular disease progression and to improve risk prediction for manifest cardiovascular diseases. Methods: The associations between (a) serum thyroid-stimulating hormone and increased exercise blood pressure, (b) serum hemoglobin A1c and endothelial dysfunction as well as (c) serum insulin-like growth factor I and endothelial dysfunction were studied using cross-sectional data from around 1400 subjects aged 25 to 85 years collected during the 5-year follow-up of the population-based Study of Health in Pomerania (SHIP-1). Increased exercise blood pressure was defined as a value above the sex- and age-specific 80th percentile measured at the 100 W stage of a symptom-limited bicycle ergometry test. Endothelial dysfunction was defined as an impaired flow-mediated dilation measured as a continuous decrease or below the median of sex-specific distribution. Non-fasting blood samples were drawn from the cubital vein in the supine position. Results: The odds for increased systolic exercise blood pressure (odds ratio 1.24, 95% confidence interval 0.88; 1.76) and diastolic exercise blood pressure (odds ratio 0.98, 95% confidence interval 0.70; 1.39) as well as for exercise-induced increase of systolic and diastolic blood pressure were not significantly different between subjects with high and low serum thyroid-stimulating hormone levels within the reference range. In women without current use of antihypertensive medication, increasing serum hemoglobin A1c levels were associated with decreasing flow-mediated dilation levels (ß = -1.17, 95% confidence interval -2.03; -0.30). Such an association was not found in men. In men, logistic regression analysis revealed an odds ratio of 1.27 (95% confidence interval 1.07; 1.51) for decreased flow-mediated dilation for each decrement of serum insulin-like growth factor I standard deviation. In women, no significant association between serum insulin-like growth factor I levels and flow-mediated dilation was observed (odds ratio 0.88, 95% confidence interval 0.74; 1.05). Conclusions: Based on the presented results it is concluded that (a) serum thyroid-stimulating hormone levels are not associated with exercise blood pressure in the general population, (b) higher serum hemoglobin A1c levels in non-diabetic subjects are inversely associated with flow-mediated dilation in women without antihypertensive medication, but not in men, and (c) lower serum insulin-like growth factor I levels are associated with impaired endothelial function in men, but not in women. Therefore the metabolic marker hemoglobin A1c and the endocrine marker insulin-like growth factor I might be markers facilitating the identification of subjects at high risk of subclinical cardiovascular alterations.
Obesity and diabetes have reached epidemic proportions and have emerged as massive public health problems globally. The etiology of both obesity and diabetes are related, multifactorial, highly complex, and involves interplay of genetic, environmental, socio-economic and physiological factors, which calls for a more extensive research in understanding the risk factors and biological pathways. Hence, this dissertation contributed in part to understanding the role of iron markers in the development of type 2 diabetes mellitus and the role of intrauterine hyperglycemia in influencing the risk of offspring obesity along with investigating potential pathways.
In the first part of my dissertation, the associations of iron markers (ferritin and transferrin) with type 2 diabetes mellitus and metabolic syndrome were investigated using the population-based Study of Health in Pomerania. The present analyses were based on 3,232 participants aged 20-81 years with a follow-up time of nearly 11 years. The results suggest that serum ferritin concentrations were associated with a higher prevalence of type 2 diabetes mellitus and metabolic syndrome in the total population as well as in men. However, the effects of serum ferritin on incident type 2 diabetes mellitus were observed only in women, while the effects on incident metabolic syndrome were seen in the total population. Serum ferritin is also known to reflect systemic inflammation or hepatic dysfunction in addition to increased iron stores. Hence, upon further analyses, the associations were found to be attenuated after adjustment for hepatic enzymes but not after adjustment for inflammation. Transferrin was not associated with any of the outcomes. Thus, our study provides evidence for a link between the iron marker ferritin and type 2 diabetes mellitus and metabolic syndrome, although the association seemed to vary by sex. Moreover, hepatic dysfunction seems likely to be in the pathway between ferritin and type 2 diabetes mellitus and metabolic syndrome.
In the second part of my dissertation, the association between maternal hyperglycemia and the risk of offspring overweight and obesity were investigated using three different cohorts: TEDDY, TEENDIAB and BABYDIAB/BABYDIET. The present analyses were based on a total of 8,103 children who were followed until 6 years of age in TEDDY study and until 18 years of age in TEENDIAB and BABYDIAB/BABYDIET studies. The dissertation revealed that maternal hyperglycemia in general may be associated with increased risk for childhood overweight and obesity, and that the association gets stronger as children grow older, with the risk being clearly evident at late childhood and adolescence. Moreover, this dissertation adds that this association can be driven by different pathways based on the type of maternal diabetes to which the offspring was exposed. The association of maternal gestational diabetes mellitus with offspring overweight can be largely explained by the confounding influence of maternal BMI, whereas the association of maternal type 1 diabetes mellitus with offspring overweight can be substantially explained by birthweight in all three studies. In our attempt to understand biological pathways at a cellular level, we found that the offspring metabolome was unlikely to be in the causal pathway between maternal type 1 diabetes mellitus and overweight, because this association could not be explained by any of the potentially relevant metabolites.
To conclude, this dissertation acknowledges the fact that prevention and early intervention of obesity and diabetes is of paramount importance to lessen the impact of these public health problems. Thus, our findings of the role of ferritin in increasing the risk of type 2 diabetes mellitus/ metabolic syndrome and the role of intrauterine hyperglycemia in increasing the risk of offspring overweight helped to identify particular risk groups who may need closer attention with respect to prevention of obesity and diabetes.
Iodine deficiency disorders (IDD) result from insufficient iodine intake, and may lead to many adverse effects on growth, development and thyroid diseases in humans.
Pakistan is a country with history of iodine deficiency.
Before reunification both parts of Germany were iodine deficient. In the Eastern part, however, due to mandatory iodine prophylaxis adaptation in 1983, the iodine status of the population improved from moderate to mild iodine deficiency. After the reunification of Germany in 1989 “voluntary principle” was adopted leading again to a decrease in iodine intake. Germany and Pakistan present different socioeconomics, cultural values and adaptations to the IDD eradication but have resemblance in history of iodine deficiency. In the recent years Germany has improved in IDD eradication more than Pakistan. The purpose of this research was to study the regional influence on iodine nutritional status of pregnant women in Pakistan and to monitor the effectiveness of the iodine fortification programme in the North-East German population.
Pregnant women data was obtained from randomly selected (public and private) prenatal clinics in five districts of the KPK province of Pakistan. Women visited there for their routine checkup between March and September 2012. Data were obtained from almost 250 pregnant women from each district reaching to a total of 1260 in all five districts.
The SHIP project consists of two population-based cohorts, for which only individuals with German citizenship and main residency in the study area were recruited. In the first SHIP cohort; SHIP-0, individuals aged 20-79 years were selected from population registries by a two-stage cluster sampling method. The net sample (without migrated or deceased persons) comprised 6265 eligible subjects, of which 4308 (response 68.8%) participated between 1997 and 2001. A separate stratified random sample of 8826 adults aged 20-79 years was drawn for SHIP-Trend, of which 4420 subjects participated between 2008 and 2012 (response 50.1%) in SHIP-Trend-0.
All the pregnant women were asked to complete a short interview questionnaire containing the information related to sources and reasons for intake and non-intake of iodized salt. The questionnaire also comprised questions related to knowledge of iodized salt nutrition. Information on the number of previous pregnancies and/or abortions (fetal loss due to various reasons, not including voluntary termination of pregnancy) was also obtained. The gestational age of the pregnant women was determined from the first day of the last regular menstrual period with gestational ages of ≤14.9, 28.9, and ≥29 weeks comprising the first, second, and third trimesters of pregnancy, respectively. For goiter assessment in pregnant women the WHO/UNICEF/IGN recommended palpation method was used. UIC was measured using a modification of the Sandell-Kolthoff reaction with spectrophotometric detection. Evaluation of group iodine status was based on median UIC categories defined by the WHO/IGN. These are: recommended – median 150-249 μg/L; mild iodine deficiency – median <150 μg/L.
For the analysis of monitoring trends of thyroid diseases in SHIP, diagnosed thyroid disorders were assessed by computer-assisted personal interviews. Medication data were obtained online using the IDOM program (online drug-database leaded medication assessment) and classified according to the Anatomical-Therapeutic-Chemical (ATC) classification system.In SHIP population goiter assessment was based on thyroid volume determined with ultrasonography. Goiter was defined as a thyroid volume exceeding 18 mL in women and 25 mL in men. Urinary iodine concentrations were measured from spot urine samples by a photometric procedure. Urinary creatinine concentrations were determined with the Jaffé method. Evaluation of group iodine status was based on median UIC categories defined by the WHO/IGN. The iodine/creatinine ratio was calculated by dividing urinary iodine by urinary creatinine concentrations. Serum TSH, fT3, fT4 levels in SHIP study were measured by an immunochemiluminescent procedure. A method comparison between the two TSH laboratory methods showed only negligible differences. High and low serum TSH levels were based on the reference range established from data for SHIP-0 (0.25 mIU/L - 2.12 mIU/L) and SHIP-TREND-0 (0.49 mIU/L - 3.29 mIU/L) respectively (21,22). Anti-TPO Abs were measured by an enzyme immunoassay in the whole SHIP study. The anti-TPO Abs status was defined as follows: normal < 60 IU/ml in men and < 100 IU/ml in women; increased > 60 IU/ml in men and > 100 IU/ml in women; positive: > 200 IU/ml in both sexes.
Thyroid ultrasonography was performed in SHIP-0 using an ultrasound VST-Gateway with a 5 MHz linear array transducer. In SHIP-Trend-0 ultrasonography was performed with a portable device using a 13-MHz linear array transducer. In both studies intra- and inter-observer reliabilities were assessed before the start of the study and semi-annually during the study. For thyroid volume all inter-observer and inter-device variabilities showed mean differences (±2 SD)of < 5% (<25%). Thyroid volume was calculated as length x width x depth x 0.479 (ml) for each lobe (26). The normal thyroid echo pattern was classified as homogeneous. A homogeneous echo pattern with reduced echogenicity was defined as hypoechogenic. Nodular changes exceeding 10 mm in diameter were defined as thyroid nodules.
Multivariable logistic regression analysis adjusting for age was used to regress the outcome measures (knowledge about IDD, iodized salt intake, UIC <150mIU/L and goiter prevalence) on regional influences (as exposure) in each specific district. These results are presented as odd ratios and their 95% confidence interval.
For the analysis in SHIP, all analyses were standardized by base-weights to account for different sampling probabilities. In SHIP-Trend-0, additionally, inverse probability weights for study participation were calculated, which were multiplied with the base-weights. Differences in median levels between SHIP-0 and SHIP-Trend-0 were tested by median regression models; prevalence differences between SHIP-0 and SHIP-Trend-0 were tested by Poisson regression models.
The majority of pregnant women (88.0%) had no knowledge about IDD. A very high (79%) percentage of pregnant women were not taking iodized salt, out of which 36.6% reported that iodized salt would negatively affect reproduction and for 17.0%, it was too expensive. Iodized salt intake in pregnant women was high in the big cities (Peshawar, Nowshehra) and in the urban areas (27.0%)
In 41.3% of the pregnant women, we observed a UIC of >150mIU/L. The median UIC level for the pregnant women was 131µg/L. The total goiter prevalence in pregnant women was 25.5%. The prevalence of UIC <150mIU/L in pregnant women did not differ between rural and urban areas. The results based on logistic regression analysis shows that the prevalence on knowledge about IDD, iodized salt intake, UIC <150mIU/L, and goiter did not differ in pregnant women between urban and rural areas. In district Lakki Marwat except, the pregnant women from urban residence had higher odds of having knowledge on IDD and iodized salt intake than their rural counterparts.
The prevalence of diagnosed thyroid disorders increased from 7.6% [CI 6.9-8.5] in SHIP-0 to 18.9% [CI 17.6-20.1] in SHIP-Trend-0. Likewise, the prevalence of thyroid medication intake increased from 6.2% [CI 5.5-7.0] to 11.1% [CI 10.1-12.2]. The median urinary iodine excretion levels decreased significantly, which was more pronounced in females than in males. The median iodine-to-creatinine ratio declined in all sex- and age-groups with stronger decrease in females than in males. The prevalence of median urinary iodine excretion levels <100µg/L increased between SHIP-0 and SHIP-Trend-0. Median serum TSH levels increased significantly between SHIP-0 and SHIP-Trend-0, resulting in a right shift of the serum TSH level distribution. The prevalence of high serum TSH levels remained almost stable between SHIP-0 and SHIP-Trend-0. Likewise, the prevalence of low TSH remained almost stable between SHIP-0 and SHIP-Trend-0. The prevalence of increased anti-TPO Abs and positive anti-TPO Abs decreased from SHIP-0 to SHIP-Trend-0 in the whole study population. The prevalence of hypoechogenic thyroid pattern decreased from SHIP-0 to SHIP-Trend-0. The median thyroid volume remained similar between SHIP-0 and SHIP-Trend-0 in the whole study population. Goiter prevalence decreased significantly; more pronounced in males than in females, while the prevalence of thyroid nodules increased between SHIP-0 and SHIP-Trend-0.
In pregnant women in Pakistan due to insufficient awareness campaigns and low literacy ratio in rural areas urinary iodine excretion levels indicate a stable iodine supply, which is still not sufficient. Our results show that rural/urban disparity is affecting the IDD prevention program in rural districts, but not in general. The SHIP data indicate that the improved iodine supply over the past two decades in Germany is paralleled by a reduction in prevalence of IDDs, while no increase was observed in markers of autoimmune thyroid disorders arguing for an optimal iodine supply of the general adult population in Northeast Germany. The increase in prevalence of diagnosed thyroid disorders and the intake of thyroid medication might be because of inappropriate therapeutical decisions which should be made with caution, based on regional TSH reference ranges, its prognostic value, and compliance with treatment.
Abstract
Background
Opioid use for chronic non‐cancer pain (CNCP) is under debate. In the absence of pan‐European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC).
Methods
The clinical practice recommendations were developed by eight scientific societies and one patient self‐help organization under the coordination of EFIC. A systematic literature search in MEDLINE (up until January 2020) was performed. Two categories of guidance are given: Evidence‐based recommendations (supported by evidence from systematic reviews of randomized controlled trials or of observational studies) and Good Clinical Practice (GCP) statements (supported either by indirect evidence or by case‐series, case–control studies and clinical experience). The GRADE system was applied to move from evidence to recommendations. The recommendations and GCP statements were developed by a multiprofessional task force (including nursing, service users, physicians, physiotherapy and psychology) and formal multistep procedures to reach a set of consensus recommendations. The clinical practice recommendations were reviewed by five external reviewers from North America and Europe and were also posted for public comment.
Results
The European Clinical Practice Recommendations give guidance for combination with other medications, the management of frequent (e.g. nausea, constipation) and rare (e.g. hyperalgesia) side effects, for special clinical populations (e.g. children and adolescents, pregnancy) and for special situations (e.g. liver cirrhosis).
Conclusion
If a trial with opioids for chronic noncancer pain is conducted, detailed knowledge and experience are needed to adapt the opioid treatment to a special patient group and/or clinical situation and to manage side effects effectively.
Significance
If a trial with opioids for chronic noncancer pain is conducted, detailed knowledge and experience are needed to adapt the opioid treatment to a special patient group and/or clinical situation and to manage side effects effectively. A collaboration of medical specialties and of all health care professionals is needed for some special populations and clinical situations.
Background: Patients of geriatrics are often treated by several health care providers at the same time. The spatial, informational, and organizational separation of these health care providers can hinder the effective treatment of these patients.
Objective: This study aimed to develop a regional health information exchange (HIE) system to improve HIE in geriatric treatment. This study also evaluated the usability of the regional HIE system and sought to identify barriers to and facilitators of its implementation.
Methods: The development of the regional HIE system followed the community-based participatory research approach. The primary outcomes were the usability of the regional HIE system, expected implementation barriers and facilitators, and the quality of the developmental process. Data were collected and analyzed using a mixed methods approach.
Results: A total of 3 focus regions were identified, 22 geriatric health care providers participated in the development of the regional HIE system, and 11 workshops were conducted between October 2019 and September 2020. In total, 12 participants responded to a questionnaire. The main results were that the regional HIE system should support the exchange of assessments, diagnoses, medication, assistive device supply, and social information. The regional HIE system was expected to be able to improve the quality and continuity of care. In total, 5 adoption facilitators were identified. The main points were adaptability of the regional HIE system to local needs, availability to different patient groups and treatment documents, web-based design, trust among the users, and computer literacy. A total of 13 barriers to adoption were identified. The main expected barriers to implementation were lack of resources, interoperability issues, computer illiteracy, lack of trust, privacy concerns, and ease-of-use issues.
Conclusions: Participating health care professionals shared similar motivations for developing the regional HIE system, including improved quality of care, reduction of unnecessary examinations, and more effective health care provision. An overly complicated registration process for health care professionals and the patients’ free choice of their health care providers hinder the effectiveness of the regional HIE system, resulting in incomplete patient health information. However, the web-based design of the system bridges interoperability problems that exist owing to the different technical and organizational structures of the health care facilities involved. The regional HIE system is better accepted by health care professionals who are already engaged in an interdisciplinary, geriatric-focused network. This might indicate that pre-existing cross-organizational structures and processes are prerequisites for using HIE systems. The participatory design supports the development of technologies that are adaptable to regional needs. Health care providers are interested in participating in the development of an HIE system, but they often lack the required time, knowledge, and resources.
Analysis based on claims data showed no clinical benefit from AGR intervention regarding theinvestigated outcomes. The slightly worse outcomes may reflect limitations in matching based on claims data,which may have insufficiently reflected morbidity and psychosocial factors. It is possible that the interventiongroup had poorer health status at baseline compared to the control group.
Background
The national Network Genomic Medicine (nNGM) Lung Cancer provides comprehensive and high-quality multiplex molecular diagnostics and standardized personalized treatment recommendation for patients with advanced non-small cell lung cancer (aNSCLC) in Germany. The primary aim of this study was to investigate the effectiveness of the nNGM precision medicine program in terms of overall survival (OS) using real-world data (RWD).
Methods
A historical nationwide cohort analysis of patients with aNSCLC and initial diagnosis between 04/2019 and 06/2020 was conducted to compare treatment and OS of patients with and without nNGM-participation. Patients participating within the nNGM (nNGM group) were selected based on a prospective nNGM database. The electronic health records (EHR) of the prospective nNGM database were case-specifically linked to claims data (AOK, German health insurance). The control group was selected from claims data of patients receiving usual care without nNGM-participation (non-nNGM group). The minimum follow-up period was six months.
Findings
Overall, n = 509 patients in the nNGM group and n = 7213 patients in the non-nNGM group met the inclusion criteria. Patients participating in the nNGM had a significantly improved OS compared to the non-nNGM group (median OS: 10.5 months vs. 8.7 months, p = 0.008, HR = 0.84, 95% CI: 0.74–0.95). The 1-year survival rates were 46.8% (nNGM) and 41.3% (non-nNGM). The use of approved tyrosine kinase inhibitors (TKI) in the first-line setting was significantly higher in the nNGM group than in the non-nNGM group (nNGM: 8.4% (43/509) vs. non-nNGM: 5.1% (366/7213), p = 0.001). Overall, patients receiving first-line TKI treatment had significantly higher 1-year OS rates than patients treated with PD-1/PD-L1 inhibitors and/or chemotherapy (67.2% vs. 40.2%, p < 0.001).
Interpretation
This is the first study to demonstrate a significant survival benefit and higher utilization of targeted therapies for aNSCLC patients participating within nNGM. Our data indicate that precision medicine programs can enhance collaborative personalized lung cancer care and promote the implementation of treatment innovations and the latest scientific knowledge into clinical routine care.
Funding
The study was funded by the AOK Federal Association Germany.
Scope
Previous work identified three metabolically homogeneous subgroups of individuals (“metabotypes”) using k‐means cluster analysis based on fasting serum levels of triacylglycerol, total cholesterol, HDL cholesterol, and glucose. The aim is to reproduce these findings and describe metabotype groups by dietary habits and by incident disease occurrence.
Methods and results
1744 participants from the KORA F4 study and 2221 participants from the KORA FF4 study are assigned to the three metabotype clusters previously identified by minimizing the Euclidean distances. In both KORA studies, the assignment of participants results in three metabolically distinct clusters, with cluster 3 representing the group of participants with the most unfavorable metabolic characteristics. Individuals of cluster 3 are further characterized by the highest incident disease occurrence during follow‐up; they also reveal the most unfavorable diet with significantly lowest intakes of vegetables, dairy products, and fibers, and highest intakes of total, red, and processed meat.
Conclusion
The three metabotypes originally identified in an Irish population are successfully reproduced. In addition to this validation approach, the observed differences in disease incidence across metabotypes represent an important new finding that strongly supports the metabotyping approach as a tool for risk stratification.