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Objectives: Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) are common in multimorbid patients. This study aims to describe PIMs and PPOs in an open-access outpatient setting and to investigate any association between continuity of care (CoC) and PIMs and PPOs in multimorbid older patients., Design: Cross-sectional study using patient-confirmed outpatient medication plans to describe PIMs and PPOs using the 'Screening Tool of Older Person's Prescription/Screening Tool to Alert to Right Treatment' version 2. Four Poisson regressions modelled the number of PIMs and PPOs using context-adapted versions of the Usual Provider of Care (UPC) and the Modified Modified Continuity Index (MMCI) as measures for CoC., Setting: Southern Germany, outpatient setting., Participants: 321 participants of the LoChro-trial at 12-month follow-up (both arms). The LoChro-trial compared healthcare involving an additional care manager with usual care. Inclusion criteria were age over 64, local residence and scoring over one in the Identification of Older patients at Risk Screening Tool., Primary Outcomes: Numbers of PIMs and PPOs., Results: The mean number of PIMs was 1.5 (SD 1.5), lower than the average number of PPOs at 2.9 (SD 1.7). CoC showed similar results for both indices with a mean of 0.548 (SD 0.279) for MMCI and 0.514 (SD 0.262) for UPC. Both models predicting PPOs indicated more PPOs with higher CoC; statistical significance was only demonstrated for MMCI (MMCI~PPO: Exp(B)=1.42, 95% CI (1.11; 1.81), p=0.004; UPC~PPO: Exp(B)=1.29, 95% CI (0.99; 1.67), p=0.056). No significant association between PIMs and CoC was found (MMCI~PIM: Exp(B)=0.72, 95% CI (0.50; 1.03), p=0.072; UPC~PIM: Exp(B)=0.83, 95% CI (0.57; 1.21), p=0.337)., Conclusion: The results did not show a significant association between higher CoC and lesser PIMs. Remarkably, an association between increased CoC, represented through MMCI, and more PPOs was found. Consultation of different care providers in open-access healthcare systems could possibly ameliorate under-prescribing in multimorbid older patients., Trial Registration: German Clinical Trials Register (DRKS): DRKS00013904., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Multimorbidity challenges healthcare systems. In Germany, coordination of healthcare for older multimorbid patients remains unstructured.This study aims to identify key themes in the healthcare of these patients and the inter-relationships between them., Design: Framework analysis of six cases based on 1-year data of primary and secondary care, patient-answered questionnaires and video material., Setting: Southern Germany., Participants: Six multimorbid older patients participating in a randomised controlled trial that compared usual care with a local, collaborative, stepped and personalised care management approach for older people with chronic diseases (LoChro-trial). The LoChro care intervention involved a care manager who assisted participants in self-management. The primary outcome was a composite of functional health and depressive symptoms at 12 and 18 months. The LoChro-intervention had no effect on the primary outcome., Primary Outcome Measure: Key themes in the healthcare of older patients with multimorbidity and the inter-relationships between them., Methods: One-year data included diagnoses, treatment plans, examinations, assessments and discharge reports. Patient perspectives were assessed using the Patient Assessment of Chronic Illness Care. In three cases, videos of the LoChro intervention showed patients describing their health needs. These data were evaluated by three doctors and public health researchers. Using framework analysis, recurring themes influencing the healthcare situation of multimorbid older patients and their inter-relationships were identified., Results: Participants had an average age of 77, with 13 diagnoses, taking eight medications regularly. The five key themes describing the healthcare situation of these multimorbid patients were as follows: insufficient coordination , overuse and underuse of medical care , doctor and patient roles . Each theme covered three to four subcategories. The most significant inter-relationships between these themes were a lack of coordination leading to overuse and underuse of medical care. These were characterised by redundant inpatient stays, potential prescribing omissions and missed examinations. Deficiencies in vaccinations and secondary prevention were also demonstrated., Conclusion: Coordination of care for multimorbid older patients in Germany is still deficient. Future healthcare arrangements should be explored with the participation of physicians and patients., Trial Registration Number: LoChro trial: DRKS00013904., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We recently designed an innovative scaffold-bioreactor unit for the bioengineering of a three-dimensional (3D) bioartificial human thyroid gland or its miniaturized replica as a part of a microfluidic chip test system. This device is based on the evidence that the 3D geometry of the intraglandular stromal/vascular scaffold (SVS; i.e., the fibrous and vascular matrix) of mammalian viscera plays a key role in guiding growth and differentiation of in vitro seeded cells. Therefore, we initiated a research program focused on computer-aided reconstruction of the 2nd to 4th order intralobar arterial network (IAN) of the human thyroid gland as a reliable surrogate for its 3D SVS, to be used as an input for rapid prototyping of a biomaterial replica. To this end, we developed a computational template that works within the Mathematica environment, giving rise to a quasi-fractal growth of the IAN distribution, constrained within an approximation of the thyroid lobe shape as a closed surface. Starting from edge detection of planar images of real human thyroid lobes acquired by in vivo real-time ultrasonography, we performed data approximation of the lobar profiles based on splines and Bezier curves, providing 3D lobar shapes as geometric boundaries for vessel growth by a diffusion-limited aggregation model. Our numerical procedures allowed for a robust connection between development of lobar arterial trees and thyroid lobe shape, led to a vascular self-similarity consistent with that of a cadaveric lobar arterial cast, and reproduced arterial vessels in a proportion not statistically different from that described for the real human thyroid gland. We conclude that our algorithmic template offers a reliable reproduction of the extremely complex IAN of the adult human thyroid lobe, potentially useful as a computational guidance for bioprinting of thyroid lobe matrix replicas. In addition, due to the simplicity and limited number of morphometrical parameters required by our system, we predict its application to the design of a number of patient-tailored human bioartificial organs and organs-on-chip, including parenchymal viscera and bones. Impact statement The study introduces the computer simulation of the three-dimensional (3D) intrinsic vascular matrix of the human thyroid gland, offering a general concept applicable to a number of other human viscera. Indeed, it provides a flexible software tool for reproduction of a 3D surrogate of the organ's 3D stromal matrix, suitable for eventual 3D bioprinting with biomaterials, and recellularization with organ-specific stem cells/progenitors. The final expectation is the design of patient-tailored 3D organ's matrices upon clinical request.

Background: An ever-increasing number of patients seek health information via the internet. However, there is an overabundance of differing, often low-quality information available, while a lack of health literacy makes it difficult for patients to understand and assess the quality and trustworthiness of the information at hand. The web portal tala-med was thus conceived as an evidence-based, up-to-date, and trustworthy information resource for lower back pain (LBP), which could be used by primary care physicians (PCPs) and patients during and following consultations for LBP. The current evidence demonstrates that patients with LBP could benefit from web portals. However, the use of such portals by patients remains low, thus limiting their effectiveness. Therefore, it is important to explore the factors that promote or hinder the use of web portals and investigate how patients perceive their usability and utility., Objective: In this study, we investigated the acceptance, usability, and utility of the web portal tala-med from the patient perspective., Methods: This qualitative study was based on telephone interviews with patients who had access to the web portal tala-med from their PCP. We used a semistructured interview guide that consisted of questions about the consultation in which patients were introduced to tala-med, in addition to questions regarding patient perceptions, experiences, and utilization of tala-med. The interviews were recorded, transcribed, and analyzed through framework analysis., Results: A total of 32 half-hour interviews were conducted with 16 female and 16 male patients with LBP. We identified 5 themes of interest: the use of tala-med by PCPs during the consultation, the use of tala-med by patients, its usability, added values derived from its use, and the resultant effects of using tala-med. PCPs used tala-med as an additional information resource for their patients and recommended the exercises. The patients appreciated these exercises and were willing to use tala-med at home. We also identified factors that promoted or hindered the use of tala-med by patients. Most patients rated tala-med positively and considered it a clear, comprehensible, trustworthy, and practical resource. In particular, the trustworthiness of tala-med was seen as an advantage over other information resources. The possibilities offered by tala-med to recap and reflect on the contents of consultations in a time-flexible and independent manner was perceived as an added value to the PCP consultation., Conclusions: Tala-med was well accepted by patients and appeared to be well suited to being used as an add-on to PCP consultations. Patient perception also supports its usability and utility. Tala-med may therefore enrich consultations and assist patients who would otherwise be unable to find good-quality web-based health information on LBP. In addition, our findings support the future development of digital health platforms and their successful use as a supplement to PCP consultations., International Registered Report Identifier (irrid): RR2-10.1186/s12875-019-0925-8., (©Christian Schlett, Nicole Röttele, Piet van der Keylen, Andrea Christina Schöpf-Lazzarino, Miriam Klimmek, Mirjam Körner, Kathrin Schnitzius, Sebastian Voigt-Radloff, Andy Maun, Mario Sofroniou, Erik Farin-Glattacker. Originally published in JMIR Formative Research (https://formative.jmir.org), 29.12.2022.)

Background: Older patients are at an increased risk of hospitalization, negatively affecting their health and quality of life. Such patients also experience a lack of physical activity during their inpatient stay, as well as being at increased risk of delirium and inappropriate prescribing. These risk factors can accumulate, promoting a degree of morbidity and the development of cognitive impairment., Methods: Through the ReduRisk-program, patients at risk of functional impairment, immobility, falls, delirium or re-hospitalization shortly after hospital discharge, will be identified via risk-screening. These patients will receive an individually tailored, multicomponent and risk-adjusted prevention program. The trial will compare the effectiveness of the ReduRisk-program against usual care in a stepped-wedge-design, with quarterly cluster randomization of six university hospital departments into intervention and control groups. 612 older adults aged 70 years or more are being recruited. Patients in the intervention cluster (n = 357) will receive the ReduRisk-program, comprising risk-adjusted delirium management, structured mobility training and digitally supported planning of post-inpatient care, including polypharmacy management. This study will evaluate the impact of the ReduRisk-program on the primary outcomes of activities of daily living and mobility, and the secondary outcomes of delirium, cognition, falls, grip strength, health-related quality of life, potentially inappropriate prescribing, health care costs and re-hospitalizations. Assessments will be conducted at inpatient admission (t0), at discharge (t1) and at six months post-discharge (t2). In the six-month period following discharge, a health-economic evaluation will be carried out based on routine health insurance data (t3)., Discussion: Despite the importance of multicomponent, risk-specific approaches to managing older patients, guidelines on their effectiveness are lacking. This trial will seek to provide evidence for the effectiveness of a multicomponent, risk-adjusted prevention program for older patients at risk of functional impairment, immobility, falls, delirium and re-hospitalization. Positive study results would support efforts to improve multicomponent prevention and the management of older patients., Trial Registration: German Clinical Trials Register, DRKS00025594, date of registration: 09/08/2021., (© 2022. The Author(s).)

Background: Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive-compulsive disorder, and a variety of anxiety disorders; it is available as an oral preparation. Fluvoxamine has not been approved for the treatment of infections, but has been used in the early treatment of people with mild to moderate COVID-19. As there are only a few effective therapies for people with COVID-19 in the community, a thorough understanding of the current evidence regarding the efficacy and safety of fluvoxamine as an anti-inflammatory and possible anti-viral treatment for COVID-19, based on randomised controlled trials (RCTs), is needed., Objectives: To assess the efficacy and safety of fluvoxamine in addition to standard care, compared to standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy for the treatment of COVID-19 outpatients and inpatients., Search Methods: We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv), Web of Science and WHO COVID-19 Global literature on COVID-19 to identify completed and ongoing studies up to 1 February 2022., Selection Criteria: We included RCTs that compared fluvoxamine in addition to standard care (also including no intervention), with standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy in clinical trials for the treatment of people with confirmed COVID-19, irrespective of disease severity, in both inpatients and outpatients. Co-interventions needed to be the same in both study arms. We excluded studies comparing fluvoxamine to other pharmacological interventions with unproven efficacy., Data Collection and Analysis: We assessed risk of bias of primary outcomes using the Cochrane Risk of Bias 2 tool for RCTs. We used GRADE to rate the certainty of evidence to treat people with asymptomatic to severe COVID-19 for the primary outcomes including mortality, clinical deterioration, clinical improvement, quality of life, serious adverse events, adverse events of any grade, and suicide or suicide attempt., Main Results: We identified two completed studies with a total of 1649 symptomatic participants. One study was conducted in the USA (study with 152 participants, 80 and 72 participants per study arm) and the other study in Brazil (study with 1497 high-risk participants for progression to severe disease, 741 and 756 participants per study arm) among outpatients with mild COVID-19. Both studies were double-blind, placebo-controlled trials in which participants were prescribed 100 mg fluvoxamine two or three times daily for a maximum of 15 days. We identified five ongoing studies and two studies awaiting classification (due to translation issues, and due to missing published data). We found no published studies comparing fluvoxamine to other pharmacological interventions of proven efficacy. We assessed both included studies to have an overall high risk of bias. Fluvoxamine for the treatment of COVID-19 in inpatients We did not identify any completed studies of inpatients. Fluvoxamine for the treatment of COVID-19 in outpatients Fluvoxamine in addition to standard care may slightly reduce all-cause mortality at day 28 (RR 0.69, 95% CI 0.38 to 1.27; risk difference (RD) 9 per 1000; 2 studies, 1649 participants; low-certainty evidence), and may reduce clinical deterioration defined as all-cause hospital admission or death before hospital admission (RR 0.55, 95% CI 0.16 to 1.89; RD 57 per 1000; 2 studies, 1649 participants; low-certainty evidence). We are very uncertain regarding the effect of fluvoxamine on serious adverse events (RR 0.56, 95% CI 0.15 to 2.03; RD 54 per 1000; 2 studies, 1649 participants; very low-certainty evidence) or adverse events of any grade (RR 1.06, 95% CI 0.82 to 1.37; RD 7 per 1000; 2 studies, 1649 participants; very low-certainty evidence). Neither of the studies reported on symptom resolution (clinical improvement), quality of life or suicide/suicide attempt., Authors' Conclusions: Based on a low-certainty evidence, fluvoxamine may slightly reduce all-cause mortality at day 28, and may reduce the risk of admission to hospital or death in outpatients with mild COVID-19. However, we are very uncertain regarding the effect of fluvoxamine on serious adverse events, or any adverse events. In accordance with the living approach of this review, we will continually update our search and include eligible trials as they arise, to complete any gaps in the evidence., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Older patients at risk of functional decline are frequently affected by polypharmacy. This is associated with a further loss of independence. However, a relationship between functional disability and medications, such as 'Potentially Inappropriate Medications' (PIMs) and 'Potential Prescribing Omissions' (PPOs), as itemised for (de) prescribing in practice-orientated medication lists, has yet to be established., Methods: As part of a randomised comparative effectiveness trial, LoChro, we conducted a cross-sectional analysis of the association between PIMs and PPOs measured using the 'Screening Tool of Older Persons' Prescription Criteria / Screening Tool To Alert to Right Treatment' (STOPP/START) Version 2, with functional disability assessed using the 'World Health Organization Disability Assessment Schedule 2.0' (WHODAS). Individuals aged 65 and older at risk of loss of independence were recruited from the inpatient and outpatient departments of the local university hospital. Multiple linear regression analysis was used to model the potential prediction of functional disability using the numbers of PIMs and PPOs, adjusted for confounders including multimorbidity., Results: Out of 461 patients, both the number of PIMs and the number of PPOs were significantly associated with an increase in WHODAS-score (Regression coefficients B 2.7 [95% confidence interval: 1.5-3.8] and 1.5 [95% confidence interval: 0.2-2.7], respectively). In WHODAS-score prediction modelling the contribution of the number of PIMs exceeded the one of multimorbidity (standardised coefficients beta: PIM 0.20; multimorbidity 0.13; PPO 0.10), whereas no significant association between the WHODAS-score and the number of medications was seen. 73.5 % (339) of the participants presented with at least one PIM, and 95.2% (439) with at least one PPO. The most common PIMs were proton pump inhibitors and analgesic medication, with frequent PPOs being pneumococcal and influenza vaccinations, as well as osteoporosis prophylaxis., Conclusions: The results indicate a relationship between inappropriate prescribing, both PIMs and PPOs, and functional disability, in older patients at risk of further decline. Long-term analysis may help clarify whether these patients benefit from interventions to reduce PIMs and PPOs., (© 2022. The Author(s).)

Objective: This scoping review has been conducted to summarise the information needs of internet users and their requirements for online health information., Methods: We searched MEDLINE, Web of Science and Scopus up to July 2019. Qualitative, quantitative and mixed-method studies were included and a thematic synthesis with category formation and exact description of the items was carried out., Results: 118 studies were included. To address all users' needs mentioned in the included studies, we grouped them into nine main categories: authority, comprehension, currency, evidence-based information, exchange with others, independence, purpose, services, user experience. The evaluation showed that website users wanted qualifications of authors to be cited. Users preferred health information that offered interactive elements and resources for relatives, whilst also providing an opportunity for online contact with others. The ease with which information was accessed and the intelligibility of texts were regarded as being very important to users., Conclusion: Given the rapid evolvement and changes of online health information, it is crucial to provide up to date insights and a comprehensive overview of the range of criteria., Practice Implications: With the results obtained through this scoping review, the creators of online health information could be assisted in providing user-specific resources., Competing Interests: Declaration of Competing Interest The authors declare no actual or potential conflict of interest including any financial, personal or other relationships with other people or organisations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epithelial–mesenchymal transition (EMT) is an essential biological process, also implicated in pathological settings such as cancer metastasis, in which epithelial cells transdifferentiate into mesenchymal cells. We devised an image analysis pipeline to distinguish between tissues comprised of epithelial and mesenchymal cells, based on extracted features from immunofluorescence images of differing biochemical markers. Mammary epithelial cells were cultured with 0 (control), 2, 4, or 10 ng/mL TGF-β1, a well-established EMT-inducer. Cells were fixed, stained, and imaged for E-cadherin, actin, fibronectin, and nuclei via immunofluorescence microscopy. Feature selection was performed on different combinations of individual cell markers using a Bag-of-Features extraction. Control and high-dose images comprised the training data set, and the intermediate dose images comprised the testing data set. A feature distance analysis was performed to quantify differences between the treatment groups. The pipeline was successful in distinguishing between control (epithelial) and the high-dose (mesenchymal) groups, as well as demonstrating progress along the EMT process in the intermediate dose groups. Validation using quantitative PCR (qPCR) demonstrated that biomarker expression measurements were well-correlated with the feature distance analysis. Overall, we identified image pipeline characteristics for feature extraction and quantification of immunofluorescence images to distinguish progression of EMT.

Background: Digitalization and the increasing availability of online information have changed the way in which information is searched for and retrieved by the public and by health professionals. The technical developments in the last two decades have transformed the methods of information retrieval. Although systematic evidence exists on the general information needs of specialists, and in particular, family physicians (FPs), there have been no recent systematic reviews to specifically address the needs of FPs and any barriers that may exist to accessing online health information., Objective: This review aims to provide an up-to-date perspective on the needs of FPs in searching, retrieving, and using online information., Methods: This systematic review of qualitative and quantitative studies searched a multitude of databases spanning the years 2000 to 2020 (search date January 2020). Studies that analyzed the online information needs of FPs, any barriers to the accessibility of information, and their information-seeking behaviors were included. Two researchers independently scrutinized titles and abstracts, analyzing full-text papers for their eligibility, the studies therein, and the data obtained from them., Results: The initial search yielded 4541 studies for initial title and abstract screening. Of the 144 studies that were found to be eligible for full-text screening, 41 were finally included. A total of 20 themes were developed and summarized into 5 main categories: individual needs of FPs before the search; access needs, including factors that would facilitate or hinder information retrieval; quality needs of the information to hand; utilization needs of the information available; and implication needs for everyday practice., Conclusions: This review suggests that searching, accessing, and using online information, as well as any pre-existing needs, barriers, or demands, should not be perceived as separate entities but rather be regarded as a sequential process. Apart from accessing information and evaluating its quality, FPs expressed concerns regarding the applicability of this information to their everyday practice and its subsequent relevance to patient care. Future online information resources should cater to the needs of the primary care setting and seek to address the way in which such resources may be adapted to these specific requirements., (©Piet van der Keylen, Johanna Tomandl, Katharina Wollmann, Ralph Möhler, Mario Sofroniou, Andy Maun, Sebastian Voigt-Radloff, Luca Frank. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.12.2020.)