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Evaluation of the “check-up 45 +” in primary care
Access through the GP practice to apply for prevention or rehabilitation services is still under-used [A range of studies developed and evaluated screening instruments for needs assessment [The following research question will be explored: can the number of applications for prevention and rehabilitation services be inc...
PMC10116757
Objectives
The aim of this study is to evaluate the effectiveness of the "check-up 45 + ". We will examine whether the "check-up 45 + " affects the number of applications for German Pension Insurance services through an early identification of needs of patients in primary care by a structured needs assessment, provision of inform...
PMC10116757
Methods
PMC10116757
Study setting
The intervention is implemented in about 20 GP practices located in Berlin and Brandenburg. Practices in rural and urban areas, each with differing social structures, participate. The practices can have different specialisations (e.g. occupational medicine, naturopathy), but are all maintained by general practitioners ...
PMC10116757
Eligibility criteria
disability
All patients aged between 45 and 59 years and insured by the German Pension Insurance Berlin-Brandenburg or the German Federal Pension Insurance can participate in the study. Further inclusion criteria are residence in Berlin or Brandenburg, contribution to social insurance for at least 6 months within the last 24 mont...
PMC10116757
Treatment
PMC10116757
Control
The control group is recruited in the same way as the intervention group but is only handed a two-page questionnaire covering socio-economic and occupational variables.
PMC10116757
Primary outcome
The primary outcome is the proportion of applications for prevention and rehabilitation services of the German Pension Insurance within two months after study participation of each patient.
PMC10116757
Secondary outcomes
Secondary outcomes are (1) the proportion of approved applications for prevention interventions and medical rehabilitation services and (2) the proportion of completed prevention interventions and medical rehabilitation services. In addition, (3) the proportion of persons with a need for prevention and rehabilitation a...
PMC10116757
Other measurements
Health-related and sociodemographic characteristics are assessed via the patient questionnaires and administrative data from the individual pension insurance account. Both groups receive a two-page questionnaire. These variables are collected for sample description, group comparison and to identify relevant covariates ...
PMC10116757
“Screening 45 + ”
PMC10116757
Dimension A—work ability
Work ability is assessed by adapted questions from the "Screening Instrument to Assess the Need for Medically and Occupationally Oriented Measures" (SIMBO) and the "Work Ability Index" (WAI). The SIMBO has already been used in numerous studies [
PMC10116757
Dimension B—mental well-being
depressive, anxiety
Mental well-being is assessed via the short form of the Patient Health Questionnaire-4 (PHQ-4). The PHQ-4 is an ultra-short screening instrument with four items to identify depressive and anxiety symptoms [
PMC10116757
Dimension C—functional ability
Functional ability is assessed via adapted questions from the generic questionnaire "Indicators of Rehab Status, Version 3" (IRES-3) [
PMC10116757
Dimension D—coping behaviour
The German Pension Insurance developed its own instrument consisting of four items to assess coping behaviour [
PMC10116757
Dimension E—physical activity
The items on physical activity are adapted from the National Health Service's “German Practice Physical Activity Questionnaire” (GPPAQ). The GPPAQ is a short self-report questionnaire that can be used to measure physical performance [
PMC10116757
Short questionnaire and administrative data
PMC10116757
Subjective health status
The subjective health status is assessed, according to a recommendation of the World Health Organization (WHO) [
PMC10116757
Previous use of rehabilitation services
The previous use of rehabilitation services may influence application behaviour [
PMC10116757
Further measurements of work ability
In the short questionnaire the current work ability compared with the lifetime best is measured by the “Work Ability Score” (WAS) [
PMC10116757
Work-related data
The German Pension Insurance provides information on voluntary contributions on days with creditable periods due to unemployment in months and the occupational status.
PMC10116757
Sociodemographic data
Further data regarding gender, age, educational and professional qualifications, subjective socio-economic status as well as primary language spoken in the household will be assessed via the short questionnaire.
PMC10116757
Sample size estimation
The calculation of the sample size is based on a research project that evaluated the psychometric properties, reliability and criterion validity of the “screening 45 + ” [In order to detect a difference between the intervention and the control group of applications for prevention and medical rehabilitation services, th...
PMC10116757
Recruitment
RECRUITMENT
Before the recruitment phase, the study team visits the GP practices for an one-hour training session on the procedure of the study. The practice staff invite patients who visit the practice for standard care and meet the inclusion criteria (age, insured status) to participate in the study. Study information, consent f...
PMC10116757
Allocation
RECRUITMENT
Block randomisation will be performed for each general practice, with the same number of patients per block. Allocation to the intervention or control group is randomised within each block (10 blocks of 10 per practice) to keep the number of case IDs balanced, even if the lists are not finished. The case IDs were gener...
PMC10116757
Blinding
RECRUITMENT
The practice staff are blinded during the recruitment process while inviting patients to the study. Once patients return the completed questionnaires, the practice staff are no longer blinded.The patients are not aware of their group assignment, as they have no knowledge of the existence of two groups. Unblinding the c...
PMC10116757
Data collection
SECONDARY, RECRUITMENT
Primary and secondary outcomes are provided by the German Pension Insurance registers and the questionnaire “screening 45 + ” (Tab. After recruitment is completed, semi-structured interviews will be conducted by telephone or in person to investigate practicability and acceptance of the “check-up 45 + ”. Practice staff,...
PMC10116757
Data management
RECRUITMENT
A detailed data protection concept was developed with the data protection officer of the German Pension Insurance Berlin-Brandenburg, which clarifies the rights of participants as well as the organisational procedures for the collection, processing and storage of data. Pseudonymised administrative data of the participa...
PMC10116757
Statistical analysis
SECONDARY
All analyses are conducted according to the intention-to-treat principle. Both descriptive and analytical statistics will be used to compare differences between the two study groups. In order to determine the comparability of the two study groups, the distribution of the socio-demographic and health-related variables w...
PMC10116757
Discussion
Needs assessment, information about and claiming of prevention and rehabilitation services to maintain work ability must take place earlier. Many studies are examining interventions to address patients with a prevention or rehabilitation need at an earlier stage. Our study uses a pragmatic approach to investigate the e...
PMC10116757
Trial status
RECRUITMENT
Recruitment has started and is currently ongoing.
PMC10116757
Acknowledgements
We thank the involved persons of the GP practices and the German Pension Insurance for their cooperation and efforts in conducting the study, and Susanne Rossek and Christin Lissat for monitoring the practices and supporting data collection. We acknowledge financial support from the Open Access Publication Fund of Char...
PMC10116757
Authors’ contributions
MB conceived the study and has driven the funding acquisition together with KS. MB is in charge of the project. MB and JB developed and specified the study design and the intervention. JB is responsible for the implementation of the intervention and data collection in the general practices. JB prepared the first draft ...
PMC10116757
Funding
Open Access funding enabled and organized by Projekt DEAL. This study is funded by the German Pension Insurance Berlin-Brandenburg, 15228 Frankfurt (Oder), Germany (grant number: 10-R-40.07.05.07.023). Funding covers personnel, material, and travel costs. The study design, data collection, data analysis, data interpret...
PMC10116757
Availability of data and materials
Primary data previously used for publications can be made available to researchers in anonymised form at the individual level after a justified and methodologically appropriate request to preha45@charite.de in accordance with data protection regulations for answering the questions formulated in the request. In accordan...
PMC10116757
Declarations
PMC10116757
Ethics approval and consent to participate
The study is carried out in accordance with the Declaration of Helsinki. The study protocol has been approved by the Ethics Committee of the Charité – Universitätsmedizin Berlin, Berlin, Germany (number: EA4/215/21). No legal or ethical concerns were identified. Informed consent will be obtain from all subjects and/or ...
PMC10116757
Consent for publication
Not applicable.
PMC10116757
Competing interests
The authors declare that they have no competing interests.
PMC10116757
References
PMC10116757
Subject terms
proven/probable IFDs, IFD, IFDs, proven/probable, ALL
ACUTE LYMPHOBLASTIC LEUKEMIA, REGRESSION, INVASIVE FUNGAL DISEASE, ADVERSE EVENT
In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enroll...
PMC9883161
Introduction
malignancy, neutropenia, ALL
ACUTE LYMPHOBLASTIC LEUKEMIA, NEUTROPENIA
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood and adolescence [Risk factors for IFD such as prolonged and profound neutropenia or extended periods of therapy with corticosteroids have been well established [
PMC9883161
Patients and methods
PMC9883161
Study population
ALL
T(9;22)
A total of 6136 children enrolled as study patients in the international, multi-center prospective randomized Phase III clinical trial AIEOP-BFM ALL2009 (EudraCT 2007-004270-43) were included in the analysis. Patients were eligible if they were older than 1 year, younger than 18 years, and were not Ph-positive (BCR/ABL...
PMC9883161
Invasive fungal disease (IFD)
IFDs, IFD
ADVERSE EVENTS
Serious adverse events (SAEs) were prospectively captured and reported by the participating institutions. According to study guidelines, IFDs were considered as SAEs, thus, reporting was mandatory. All SAE reports were reviewed and classified by the safety desk of the clinical trial office in Germany (AM/JA), and all S...
PMC9883161
Statistical analysis
death
MALIGNANT NEOPLASM, EVENT, REMISSION
Event-free survival (EFS) was calculated from diagnosis to first event, defined as death during induction therapy, resistance, relapse, death in complete remission, or development of a second malignant neoplasm. Overall survival rates were calculated according to Kaplan–Meier and compared by log-rank test [
PMC9883161
Results
PMC9883161
Incidence and risk factors for IFD
AIEOP-BFM
In 6136 children treated as study patients in the clinical trial AIEOP-BFM ALL2009, a total of 419 SAEs reported on a suspected IFD. Out of these, 381 were identified as the first episode of a possible (
PMC9883161
Consort diagram of patients (pts) treated according to the clinical trial AIEOP-BFM 2017 and analyzed for possible, probable and proven invasive fungal disease (IFD).
infection, PcP
YEAST INFECTION, INFECTION, ADVERSE EVENT
*Yeast infection includes two patients with more than one yeast isolates. **Mold infection includes nine patients with more than one mold isolated. SAE severe adverse event, PcP Patient´s characteristics.The 2591 girls (42.3%) and 3536 boys (57.7%) with a median age (range) of 5.2 years (1-18) were treated in Germany (...
PMC9883161
Invasive fungal disease (IFD) in the different treatment phases (protocol I, II, III and HR cycles, respectively) in standard (SR) and intermedium risk (MR) patients (above) and high risk (HR) patients (below).
proven/probable, IFDs, infections
REGRESSION, INFECTIONS
Shown are the absolute number of possible (blue), probable and proven yeast (orange) and probable/proven mold (grey) infections (Y axis). The percentages refer to the total number of IFDs in the respective risk groups (SR/MR and HR).Logistic regression revealed that the risk for proven/probable IFD was significantly in...
PMC9883161
Impact of IFD on duration of intensive chemotherapy
proven/probable, IFD
Compared to patients without IFD, patients with proven/probable and patients with possible IFD had a significantly longer duration of intensive chemotherapy (measured from start of intensive chemotherapy until start of maintenance therapy). The median duration (years; 1. and 3. quartile) of intensive chemotherapy was 0...
PMC9883161
Outcome
proven/probable, infection
INFECTION
A total of 24 and 25 patients suffering from proven/probable IFD did not survive the infection after 6 and 12 weeks, accounting for a 6-week and 12-week mortality rate of 10.7% and 11.2%, respectively (Fig. 
PMC9883161
Cumulative incidence of death from possible (blue), probable (red) and proven (green) invasive fungal disease (IFD) in children treated for acute lymphoblastic leukemia.
proven/probable
MINIMAL RESIDUAL DISEASE
The In the multivariate analysis, the hazard ratio [95% confidence interval (CI)] for 5-year EFS was significant for proven/probable IFD (1.86, 1.42-2.45), age ≥12 years (1.14, 1.07–1.21), insufficient response to therapy [blast count on day 15 measured by flow- cytometry ≥10% (1.52, 1.26–1.82) or minimal residual dise...
PMC9883161
Discussion
IFD, neutropenia, proven/probable IFD, cancer, AML, ALL
ACUTE MYELOID LEUKEMIA, NEUTROPENIA, CANCER, PEDIATRIC ALL, AML, INVASIVE ASPERGILLOSIS
In the prospective, randomized multi-international clinical trial AIEOP-BFM ALL2009 enrolling 6136 children with ALL, the reported overall incidence of proven/probable IFD and proven/probable/possible IFD was 3.8% and 6.2%, respectively, but was significantly higher in various subgroups, e.g., in older children and ado...
PMC9883161
Conclusion
proven/probable IFD, ALL
PEDIATRIC ALL
In conclusion, our data show that the overall incidence rate of IFD in pediatric ALL is relatively low, but independent risk factors such as older age and treatment-response can define high risk groups for IFD. Based on this characterization of risk groups, randomized trials on antifungal prophylaxis can be designed, w...
PMC9883161
Supplementary information
The online version contains supplementary material available at 10.1038/s41375-022-01768-x.
PMC9883161
Acknowledgements
Cancer
CANCER
The clinical trial AIEOP-BFM ALL2009 has been supported by grant No. 108588 of the Deutsche Krebshilfe, Bonn, Germany. We also wish to thank the Israel Cancer Association and the Chaim Association for their support.
PMC9883161
Author contributions
SE, NB
TL designed the research, collected the data, analyzed the data, wrote the manuscript, critically read and discussed the manuscript and approved the final version of the manuscript. AHG designed the research, collected the data, analyzed the data, wrote the manuscript, critically read and discussed the manuscript and a...
PMC9883161
Funding
Open Access funding enabled and organized by Projekt DEAL.
PMC9883161
Data availability
Under the permission that national data protection requirements are fully met, access to individual data may be made available upon reasonable request to the authors.
PMC9883161
COMPETING INTERESTS
TL has received grants from Gilead Sciences, has served as consultant to Gilead Sciences, Merck/MSD, Pfizer, Astellas, AstraZeneca and Roche, and served at the speaker´s bureau of Gilead Sciences, Merck/MSD, Astellas, Pfizer and GSK. AHG has received grants from Gilead, Merck, Sharp & Dohme and Pfizer and has served as...
PMC9883161
References
PMC9883161
Background
Depression, diabetic, death
Depression is more common in diabetic patients, with a 1.5-fold increased risk of death.
PMC10152712
Methods
depression, type 2 diabetes mellitus
TYPE 2 DIABETES MELLITUS
In this double-blind clinical trial, 60 volunteer patients (age range 20–65 years) with type 2 diabetes mellitus with symptoms of depression were randomized into the intervention (received 700 mg/day hydroalcoholic extract;
PMC10152712
Results
Sixty participants received
PMC10152712
Trial registration
All protocols in this study were followed in accordance with the Helsinki Declaration (1989 revision). Ethical approval for this study was obtained from the Iran University of Medical Sciences Ethics committee (IR.IUMS.FMD.REC 1396.9413468004; research.iums.ac.ir). The study was registered at the Iranian Registry of Cl...
PMC10152712
Supplementary Information
The online version contains supplementary material available at 10.1186/s12906-023-03978-x.
PMC10152712
Keywords
PMC10152712
Materials and methods
PMC10152712
Preparation of plant extract
The In brief, to the determination of total flavonoids and the main component of Besides, the amount of rosmarinic acid in the extract capsule was quantified by HPLC according to previously detailed techniques [
PMC10152712
Ethics approval and consent to participate
All protocols in this study were followed conducted in accordance with the Helsinki Declaration (1989 revision) and Ethical approval for this study was obtained from the Iran University of Medical Sciences Ethics committee (IR.IUMS.FMD.REC 1396.9413468004; research.iums.ac.ir). The study was registered at the Iranian R...
PMC10152712
Participants
depression, Depression, depressive
MAY, TYPE 2 DIABETES
Participants were 60 patients with type 2 diabetes combined with depression. The study was carried out at the Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences in Tehran, between May 2017 and May 2019. The Inclusion criteria were: type 2 diabetes patients with at ...
PMC10152712
Study design
BLOOD
We conducted a single-center, randomized, and double-blind clinical trial. Participants, researchers, and statisticians were blinded. All subjects were initially randomly assigned by simple randomization procedures (computerized random numbers) to the intervention group (Patients in Furthermore, the validated Persian l...
PMC10152712
Sample size
depression
A sample size of at least 25 patients per group was calculated, giving a power of 80% to detect the target difference in depression (as a critical variable obtained from a previous study) [Patients were assigned into two groups using permuted block randomization with two size blocks (case and control) and a random numb...
PMC10152712
Laboratory analysis
FBS was calculated with a Cobas MIRA analyzer (Roche Diagnostic, Basel, Switzerland) by an enzymatic process (Pars Azmon Co., Tehran, Iran). The sensitivity of the assays for FBS was 5 mg/dL. hs-CRP was calculated by using the turbidimetric method the Pars Azmoon kit (Pars Azmoon Inc., Tehran, Iran) on Hitachi 917. The...
PMC10152712
Statistical analysis
The Kolmogorov–Smirnov test was done to investigate the normality of data. Between‐group comparisons of quantitative variables and their mean changes were made using independent samples t-test or Mann–Whitney U test for normally and non-normally distributed data, respectively. A Comparison of qualitative variables and ...
PMC10152712
Results
PMC10152712
Extract analysis
The total flavonoid contents of
PMC10152712
Discussion
death, anxiety, diabetic, depression, diabetes
ADVERSE EVENTS, DISORDERS, DIABETES
The incidence of depression in diabetic patients significantly impacts glycemic control, adverse events, and quality of life in these patients. The combination of diabetes and depression increases the risk of death in these patients. We performed this study as the first clinical trial to reveal the clinical efficacy of...
PMC10152712
Strengths and limitations
Evaluation of dietary intakes and physical activity in the baseline, middle, and end of the study can be counted as the powers of our research; Nevertheless, inadequate
PMC10152712
Conclusions
The results of this study showed that the use of 700 mg of the hydroalcoholic extract of the aerial parts of
PMC10152712
Acknowledgements
The authors hereby appreciate all the volunteers who participated in this study. The authors would like to gratefully acknowledge the Institute of Medical PlantsJahadDaneshgahi and the nursing staff of the Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, for their assistance...
PMC10152712
Authors' contributions
Conceptualization has conducted by Mostafa Safari, Akbar Asadi, NaheedAryaeian/. Methodology has conducted by Mostafa Safari, Akbar Asadi, NaheedAryaeian, Farzadshidfar, ShimaJazayeri, MojtabaMalek, Hasan FallahHuseini, AghaFateme Hosseini. Validation has conducted by NaheedAryaeian, Farzadshidfar, ShimaJazayeri, Mojta...
PMC10152712
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
PMC10152712
Availability of data and materials
All data generated or analysed during this study are included in this published article [and its supplementary information files].
PMC10152712
Declarations
PMC10152712
Ethics approval and consent to participate
All protocols in this study were followed conducted in accordance with the Helsinki Declaration (1989 revision)and Ethical approval for this study was obtained from the Iran University of Medical Sciences Ethics committee (IR.IUMS.FMD.REC 1396.9413468004; research.iums.ac.ir). The study was registered at the Iranian Re...
PMC10152712
Consent for publication
We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. The manuscript has been read and approved by all the mentioned authors. All subjects gave informed consent and patient’s anonymity was preserved.
PMC10152712
Competing interests
The authors declared no conflict of interest.
PMC10152712
References
PMC10152712
Background
metabolic disease, diabetes mellitus, T2DM, metabolic anomaly
DIABETES MELLITUS
Edited by: Raffaella Maria Gadaleta, University of Bari Aldo Moro, ItalyReviewed by: Cosmin Mihai Vesa, University of Oradea, Romania; Ryan Russell, The University of Texas Rio Grande Valley, United StatesType 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, ther...
PMC10556527
Methods
MR, T2DM
The summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Invers...
PMC10556527
Results
The outcomes from the IVW analysis demonstrated that the genus
PMC10556527
Conclusion
This MR study relies on genetic variation tools to confirm the causal effect of genus
PMC10556527
1. Introduction
obesity, MR, T2DM, intestinal flora disorders
OBESITY, DISEASE, DIABETES MELLITUS (DM), METABOLIC DISEASES, TYPE 2 DIABETES MELLITUS
As society progresses and living conditions improve, increased obesity rates, declining air quality, and an aging population are risk factors for a range of chronic metabolic diseases. One of such a globally prevalent disease is diabetes mellitus (DM), which includes type 2 diabetes mellitus (T2DM) (Gut flora, the coll...
PMC10556527
2. Methods
PMC10556527
2.1. Data sources
TYPE 2 DIABETES
In our research, we conducted two-sample MR analyses, designating gut microbiota as the exposure and type 2 diabetes as the outcome variable. The exposure data was sourced from MiBioGen (
PMC10556527
2.2. Experimental design
SE, MR, T2DM
In an effort to explore the cause-and-effect link between intestinal microflora and T2DM, a bi-sample Mendelian Randomization study was implemented, leveraging data from the MiBioGen consortium and the compiled dataset from GWAS. The instrumental variables (IVs) were initially subjected to a screening process. For an I...
PMC10556527
2.3. Statistical analysis
WME, T2DM
REGRESSION
Within the framework of this research, a diverse array of methodologies was employed to explore the potential causal relationship between the gut microbiota and T2DM. These techniques encompassed an assortment of approaches, including but not limited to inverse variance weighted (IVW), Simple mode, MR-Egger regression,...
PMC10556527
2.4. Sensitivity analysis
To confirm the dependability of our outcomes, we performed sensitivity checks to gauge the sturdiness of the results, possible biases (like genetic pleiotropy and data diversity), and the impact of particular instrumental variables on the result variable (
PMC10556527