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Tim Bothe,1 Anne-Katrin Fietz,2 Elke Schaeffner,1 Antonios Douros,3– 5 Anna Pöhlmann,2 Nina Mielke,1 Cédric Villain,1,6 Muhammad Helmi Barghouth,1 Volker Wenning,7 Natalie Ebert1 1Institute of Public Health, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada; 4Institute of Clinical Pharmacology and Toxicology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 5Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada; 6Normandie Univ UNICAEN, INSERM U1075 COMETE, service de Gériatrie, CHU de Caen, Caen, France; 7AOK Nordost – Die Gesundheitskasse, Potsdam, GermanyCorrespondence: Tim Bothe, Charité – Universitätsmedizin Berlin, Institute of Public Health, Charitéplatz 1, Berlin, DE-10117, Germany, Tel +49 30 450 570054, Email tim.bothe@charite.dePurpose: The validity of ICD-10 diagnostic codes for chronic kidney disease (CKD) in health claims data has not been sufficiently studied in the general population and over time.Patients and Methods: We used data from the Berlin Initiative Study (BIS), a prospective longitudinal cohort of community-dwelling individuals aged ≥ 70 years in Berlin, Germany. With estimated glomerular filtration rate (eGFR) as reference, we assessed the diagnostic validity (sensitivity, specificity, positive [PPV], and negative predictive values [NPV]) of different claims-based ICD-10 codes for CKD stages G3-5 (eGFR < 60mL/min/1.73m²: ICD-10 N18.x-N19), G3 (eGFR 30–< 60mL/min/1.73m²: N18.3), and G4-5 (eGFR < 30mL/min/1.73m²: N18.4– 5). We analysed trends over five study visits (2009– 2019).Results: We included data of 2068 participants at baseline (2009– 2011) and 870 at follow-up 4 (2018– 2019), of whom 784 (38.9%) and 440 (50.6%) had CKD G3-5, respectively. At baseline, sensitivity for CKD in claims data ranged from 0.25 (95%-confidence interval [CI] 0.22– 0.28) to 0.51 (95%-CI 0.48– 0.55) for G3-5, depending on the included ICD-10 codes, 0.20 (95%-CI 0.18– 0.24) for G3, and 0.36 (95%-CI 0.25– 0.49) for G4-5. Over the course of 10 years, sensitivity increased by 0.17 to 0.29 in all groups. Specificity, PPVs, and NPVs remained mostly stable over time and ranged from 0.82– 0.99, 0.47– 0.89, and 0.66– 0.98 across all study visits, respectively.Conclusion: German claims data showed overall agreeable performance in identifying older adults with CKD, while differentiation between stages was limited. Our results suggest increasing sensitivity over time possibly attributable to improved CKD diagnosis and awareness.Keywords: CKD, diagnostic validity, health claims data, sensitivity, specificity

Objective: Accurate measurement of arterial blood pressure (BP) is crucial for the diagnosis, monitoring, and treatment of hypertension. This narrative review highlights the challenges associated with conventional (cuff-based) BP measurement and potential solutions. This work covers each method of cuff-based BP measurement, as well as cuffless alternatives, but is primarily focused on ambulatory BP monitoring. Results: Manual BP measurement requires stringent training and standardized protocols which are often difficult to ensure in stressful and time-restricted clinical office blood pressure monitoring (OBPM) scenarios. Home Blood pressure monitoring (HBPM) can identify white-coat and masked hypertension but strongly depends on patient adherence to measurement techniques and procedure. The widespread use of nonvalidated automated HBPM devices raises further concerns about measurement accuracy. Ambulatory blood pressure measurement (ABPM) may be used in addition to OBPM. It is recommended to diagnose white-coat and masked hypertension as well as nocturnal BP and dipping, which are the BP values most predictive for major adverse cardiac events. Nonetheless, ABPM is limited by its non-continuous nature and susceptibility to measurement artefacts. This leads to poor overall reproducibility of ABPM results, especially regarding clinical parameters such as BP variability or dipping patterns. Conclusions: Cuff-based BP measurement, despite some limitations, is vital for cardiovascular health assessment in clinical practice. Given the wide range of methodological limitations, the paradigm's potential for improvement is not yet fully realized. There are impactful and easily incorporated opportunities for innovation regarding the enhancement of measurement accuracy and reliability as well as the clinical interpretation of the retrieved data. There is a clear need for continued research and technological advancement to improve BP measurement as the premier tool for cardiovascular disease detection and management. PLAIN LANGUAGE SUMMARY: Accurate blood pressure measurement is crucial for diagnosing, monitoring, and treating hypertension and preventing cardiovascular diseases. Manual blood pressure monitoring is common but may not always be reliable due to the stress and time constraints in clinical settings. It also fails to detect white-coat and masked hypertension. Home blood pressure monitoring helps to identify white-coat and masked hypertension but depends on how well patients follow the measurement instructions. Many devices are not validated, raising concerns about their accuracy. Ambulatory blood pressure measurement may be used in addition to office blood pressure measurement because of its better reproducibility and higher predictive value. It is recommended to diagnose white-coat and masked hypertension as well as nocturnal BP and dipping. However, it and can be prone to errors, affecting the reliability of results like BP variability or night-time dipping patterns. Patient's posture, physical activity, and conditions like atrial fibrillation can influence BP readings. Automated BP devices often have limitations in detecting measurement artefacts, underscoring the need for technological improvements. Despite its limitations, cuff-based blood pressure measurement is essential in everyday clinical practice but has unlocked potential for improvement. [ABSTRACT FROM AUTHOR]

This study explores the synthesis, characterization, and biomedical applications of silver nanoparticles (AgNPs) synthesized using Simarouba glauca leaf extract. The biogenic AgNPs were characterized through UV–visible spectroscopy, X-ray diffraction (XRD), particle size analysis, zeta potential analysis, energy dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and high-resolution transmission electron microscopy (HR-TEM). The nanoparticles exhibited a distinct absorbance peak at 413.5 nm, confirming their synthesis and surface plasmon resonance. XRD and HR-TEM analyses revealed a face-centered cubic structure with an average size of 12.45 nm, while AFM indicated a mean particle size of 18.34 nm. The particles demonstrated moderate stability with a zeta potential of −41.4 mV and exhibited various elemental compositions as confirmed by EDX. In the biomedical evaluation, the anticancer potential of SG-AgNPs was tested on L-132 and A549 cell lines using MTT, live/dead, and DNA damage assays. Results showed dose-dependent cytotoxicity, with significant effects observed at higher concentrations, particularly against A549 cells. Additionally, the protective effects of SG-AgNPs were assessed in Caenorhabditis elegans using survival and paralysis assays. The nanoparticles significantly improved survival rates and reduced paralysis in worms infected with Pseudomonas aeruginosa PAO1 and Staphylococcus aureus. These findings highlight the potential of biogenic SG-AgNPs as effective agents with both anticancer and antimicrobial properties. Future research should focus on elucidating the mechanisms underlying these effects and optimizing their therapeutic applications.

Clitoria ternatea L. flowers were used for the green synthesis of silver nanoparticles (CT-AgNPs) with a focus on their anticancer and antimicrobial properties. The CT-AgNPs were characterized using a variety of techniques, including UV–Vis spectroscopy, XRD, EDX, TEM, FTIR, and DLS, revealing spherical, polycrystalline nanoparticles with an average size of 16 nm and excellent colloidal stability. Anticancer activity was assessed on A549 and L-132 cell lines, demonstrating a dose-dependent cytotoxic effect on A549 cells with an LC50 of 4.88 μg mL−1, while the CT-AgNPs exhibited no significant toxicity towards L-132 cells up to 30 μg mL−1. Additionally, the antibacterial potential of CT-AgNPs was evaluated using Caenorhabditis elegans survival assays, where they significantly reduced paralysis rates and improved nematode survival when exposed to pathogenic bacteria (Pseudomonas aeruginosa and Staphylococcus aureus) at concentrations of 20 and 40 μg mL−1. The results highlight the promising dual therapeutic potential of CT-AgNPs for both anticancer and antimicrobial applications, with future directions focusing on in vivo validation and exploration of their molecular mechanisms in higher biological systems.

Abstract In recent years, carbon quantum dots (CQDs) have garnered considerable attention as a promising material for biomedical applications because of their unique optical and biological properties. In this study, CQDs were derived from the leaves of Hibiscus rosa-sinensis Linn. via microwave-assisted technique and characterized using different techniques such as ultraviolet–visible, Fourier transform infrared, fluorescence spectrometry, X-ray diffraction, dynamic light scattering, transmission electron microscopy and energy-dispersive X-ray spectroscopy. Subsequently, their potential for biomedical applications was investigated through in vitro assays assessing scratch healing, anti-inflammatory, antibacterial, and cytotoxicity properties. It was found that the CQDs were fluorescent, polycrystalline, quasi-spherical, ~ 12 nm in size with presence of –OH and –COOH groups on their negatively charged surfaces, and demonstrated good anti-inflammatory by inhibiting protein denaturation, cyclooxygenase-2 and regulating inflammatory cytokines. The CQDs also exhibited antimicrobial activity against Klebsiella pneumoniae and Bacillus cereus, good biocompatibility, along with excellent promotion of cell proliferation in vitro, indicating their potential as a anti-inflammatory and wound healing material. The properties were more enhanced than their precursor, H. rosa-sinensis leaf extract. Hence, the CQDs synthesized from the leaves of H. rosa-sinensis can serve as a potential biomedical agent.

The study explores the green synthesis and characterization of silver nanoparticles using Syzygium malaccense (L.) Merr. & L. M. Perry leaf extract (SM-AgNPs). UV-Visible spectroscopy confirmed the reduction of silver ions, showing an absorption peak at 406 nm. X-ray Diffraction (XRD) analysis revealed a face centered cubic structure with an average particle size of 23.55 nm. Dynamic Light Scattering (DLS) and zeta potential analyses indicated a mean size of 40.1 nm and a surface charge of −40.1 mV. FTIR spectroscopy identified functional groups involved in nanoparticle stabilization, while Energy Dispersive X-ray (EDX) analysis confirmed silver content. Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM) provided detailed insights into particle morphology. Anticancer assays showed dose-dependent cytotoxicity against A549 cancer cells (LC50: 7.62 μg mL−1) with minimal effects on L-132 normal cells (LC50: 73.55 μg mL−1), highlighting selectivity. Additionally, SM-AgNPs increased Caenorhabditis elegans survival and reduced paralysis under pathogenic bacterial exposure. This study demonstrates the potential of SM-AgNPs in biomedical applications, emphasizing selective anticancer activity and antimicrobial effects in vivo.

The weed Martynia annua traditionally known as Kakanasika is annual herbaceous plant known for its multiple medicinal properties such as anthelmintic, analgesic, antipyretic, antibacterial, anti-convulsant, anti-fertility, antinociceptive, antioxidant, CNS depressant and wound healing activity. The aqueous root extract of M. annua was subjected to qualitative analysis, revealing the presence of terpeniods, indicative of its rich phytochemicals composition. Utilizing a green synthesis approach, silver nanoparticles (AgNPs) were successfully synthesized from the plant extract. Characterization through UV-Visible spectroscopy, FTIR, DLS, and SEM/EDX confirmed the formation of AgNPs with polygonal morphology and an average size of 64 nm, with the PDI of 0.385. Additionally, the AgNPs demonstrated moderate stability, evidenced by a zeta potential of −21.6 mV. Evaluation of the synthesized AgNPs focused on their anti-diabetic potential. The green synthesized R-AgNPs were potent antioxidant agents. They exhibited significant inhibition of alpha amylase, a pivotal enzyme in carbohydrate metabolism, suggesting their efficacy as anti-diabetic agents. Moreover, the AgNPs enhanced glucose uptake by yeast cells, indicating their promising therapeutic role in managing diabetes mellitus. This study highlights the pharmacological importance of M.annua, particularly its aqueous root extract, in the eco-friendly synthesis of AgNPs with potential therapeutic implications. Further investigation into the mechanism of action and clinical efficacy of these AgNPs in diabetes management is warranted.

Background: The development of clinical guidelines aimed at GPs is a key strategy to improving the management of chronic kidney disease (CKD). In 2019, the first CKD guideline aimed specifically at GPs practicing in Germany was published by the German College of General Practitioners and Family Physicians (DEGAM.) AIMS: The aim of this study is to identify the barriers and enablers for the implementation of this guideline. The results of this project, together with quantitative evaluation against quality indicators for CKD in primary care will inform an update to the guideline., Methods: We performed 17 semi-structured interviews with GPs practicing in Berlin and Brandenburg. Transcripts were analysed using qualitative content analysis as described by Mayring., Results: We found that the perception of low clinical priority of CKD compared to other chronic diseases, opportunity cost of using guidelines, as well as poor patient understanding were significant barriers. GPs expressed that improved graphic design or integration of guideline recommendations in clinical decision support systems were enabling factors. Clinical problems concerning CKD were mostly solved by recourse to informal communication with specialists. GPs reported that they rarely consulted CKD guidelines as an aide to clinical decision making., Conclusion: The most significant barrier to use was that guidelines were not used as step-by-step decision aide in consultations with patients. Our analysis suggests that informal contact between primary and secondary care is significant conduit for evidence-based information on CKD in German primary care. Implementation projects should support the development of these relationships., (© 2024. The Author(s).)

Objectives: Despite the growing evidence regarding the influence of social factors on frailty in older adults, the effect of social support remains unclear. This study aims to assess the association between social support and frailty progression (transition and incidence) in a sample of community-dwelling older adults., Methods: Using a cohort study design, 1,059 older adults from the Berlin Initiative Study were followed up for 2.1 years. Multinomial and logistic regression analyses were performed to assess the association of social support using Oslo Social Support Scale-3 with frailty transition and incidence, respectively. Gender differences were explored using stratified analyses., Results: At baseline, frailty prevalence in the study population [mean (SD) age 84.3 (5.6) years; 55.8% women] reached 33.1% with 47.0, 29.4 and 23.6% of the participants reporting moderate, strong and poor social support, respectively. Over the follow-up period, social support was not significantly associated with the frailty transition categories in the adjusted model. Conversely, the adjusted logistic regression analysis showed that participants with poor social support had twice the odds of becoming frail compared to those with strong social support (OR 2.07; 95% CI 1.08-3.95). Gender-stratified analyses showed comparable estimates to the main analysis but were statistically non-significant., Discussion: Our study results underpin the role of social factors in frailty incidence and highlight social support as a potential target for frailty-preventing interventions in older adults. Therefore, it is important to adopt a biopsychosocial model rather than a purely biomedical model to understand and holistically improve the health of community-dwelling older adults., Competing Interests: NE received honoraria as member of an EAB for Bayer AG, Leverkusen. ES receives honoraria from AstraZeneca and from the National Kidney Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barghouth, Klein, Bothe, Ebert, Schaeffner and Mielke.)

Background: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults., Methods: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m 2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD., Results: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12)., Conclusions: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD., (© 2024. The Author(s).)

Background: Chronic kidney failure (CKF) is often treated with dialysis, which is invasive and costly and carries major medical risks. The existing studies of patients with CKF requiring dialysis that are based on claims data from German statutory health insurance (SHI) carriers employ varying definitions of this entity, with unclear consequences for the resulting statistical estimates., Methods: We carried out a cohort study on four random samples, each consisting of 62 200 persons aged 70 or above, from among the insurees of the SHI AOK Nordost, with one sample for each of the years 2012, 2014, 2016, and 2018. The prevalence, incidence, mortality, and direct health care costs of CKF requiring dialysis were estimated and compared on the basis of four different definitions from literature and a new definition developed by the authors in reference to billing data., Results: The different definitions led to variation in 12-month prevalences (range: 0.33-0.61%) and 6-month incidences (0.058-0.100%). The percentage of patients with prior acute kidney injury (AKI) ranged from 27.6% to 61.8%. Among incident patients, three-month survival ranged from 70.2% to 88.1%, and six-month survival from 60.5% to 81.3%. In CKF patients without prior AKI, the survival curves differed less across definitions (80.2-91.8% at three months, 70.7-84.4% at six months). The monthly health care costs ranged from €6010 to €9606, with marked variability across definitions in the costs of inpatient and outpatient care., Conclusion: The lack of a standardized definition of CKF requiring dialysis in German SHI claims data leads to variability in the estimated case numbers, mortality, and health care costs. These differences are most probably in part due to the variable inclusion of inpatients who received short-term dialysis after AKI.

Background: The Cockcroft-Gault equation (CrCl C-G ) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF)., Methods: Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated CrCl C-G and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status., Results: A total of 224 patients were included in the analysis (median age 87 years). Using CrCl C-G , 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using CrCl C-G and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using CrCl C-G or eGFR., Conclusion: In older adults with AF, the association of DOAC dose status with adverse events did not differ when using CrCl C-G or eGFR. Our results suggest that eGFR equations are not inferior to CrCl C-G within this context., Competing Interests: N.E. received fees from Bayer AG Leverkusen as a member of an editorial advisory board outside the submitted work. E.S. received a research grant from Bayer unrelated to the topic of the article and receives a stipend from the National Kidney Foundation. The other authors declare no conflicts of interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: To investigate what competencies and attributes preregistrant pharmacists draw upon in job interviews., Methods: We used a virtual mock job interview assessment asking preregistrant pharmacists to apply for an entry-level pharmacist position. Data were analyzed using a team-based framework analysis using an inductive and deductive approach and mapping responses to the National Competency Standards., Results: A total of 143 interview transcripts were included in the analysis. The top skills mentioned were leadership of self (98.6%) and communication and collaboration (96.5%). Despite graduating from a course with an integrated research curriculum, participants rarely reflected on research skills (31.5%) and no participant discussed any expertise in clinical topics or knowledge of specific professional services. Responses generally lacked specific skills and skills were spoken about broadly without relating to evidence/experience and were often not targeted to the job description. A proposal for educators aligned with competency standards was also developed based on the findings., Conclusion: Preregistrant pharmacists perceive experience within the workforce and communication and collaboration as the most desired by employers for entry-level pharmacy positions. Education and research competencies were seen as least useful to the job. There was a disconnect between skills gained in university and translation to practice. Academics could enhance the better preregistrant pharmacists' reflection of the skills and competencies they have developed employability by (1) providing portfolio management from the beginning of the course that collects evidence and maps to competencies; (2) integrating learning opportunities across all competencies; and (3) regular skills coaching/mentoring from practicing pharmacists to ensure students are aware of current needs in the job market., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2023 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Polypharmacy is associated with poorer self-rated health (SRH). However, whether polypharmacy has an impact on the SRH progression is unknown. This study investigates the association of polypharmacy with SRH change in 1428 participants of the Berlin Initiative Study aged 70 years and older over four years. Polypharmacy was defined as the intake of ≥5 medications. Descriptive statistics of SRH-change categories stratified by polypharmacy status were reported. The association of polypharmacy with being in SRH change categories was assessed using multinomial regression analysis. At baseline, mean age was 79.1 (6.1) years, 54.0% were females, and prevalence of polypharmacy was 47.1%. Participants with polypharmacy were older and had more comorbidities compared to those without polypharmacy. Over four years, five SRH-change categories were identified. After covariate adjustment, individuals with polypharmacy had higher odds of being in the stable moderate category (OR 3.55; 95% CI [2.43-5.20]), stable low category (OR 3.32; 95% CI [1.65-6.70]), decline category (OR 1.87; 95% CI [1.34-2.62]), and improvement category (OR 2.01; [1.33-3.05]) compared to being in the stable high category independent of the number of comorbidities. Reducing polypharmacy could be an impactful strategy to foster favorable SRH progression in old age.

Exact geometric calibration of optical devices like projectors or cameras is the basis for utilizing them in quantitative metrological applications. The common state-of-the-art photogrammetric pinhole-imaging-based models with supplemental polynomial corrections fail in the presence of nonsymmetric or high-spatial-frequency distortions and in describing caustics efficiently. These problems are solved by our vision ray calibration (VRC), which is proposed in this paper. The VRC takes an optical mapping system modeled as a black box and directly delivers corresponding vision rays for each mapped pixel. The underlying model, the calibration process, and examples are visualized and reviewed, demonstrating the potential of the VRC.

The advantages of spatial phase shifting (SPS) compared with temporal phase shifting in the field of electronic speckle pattern interferometry are described. Some periodic phase reconstruction errors occurring in SPS are discussed. It is shown that these errors become minimal for a spatial phase-shift angle of 2pi/3. Furthermore, a modified phase reconstruction formula is presented by which the noise in the reconstructed phase map is reduced.