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Unlike adult mammals, the hearts of neonatal mice possess the ability to completely regenerate from myocardial infarction (MI). This observation has sparked vast interest in deciphering the potentially lifesaving and morbidity-reducing mechanisms involved in neonatal cardiac regeneration. In mice, the regenerative potential is lost within the first week of life and coincides with a reduction of Insulin-like growth factor 1 receptor (Igf1r) expression in the heart. Igf1r is a well-known regulator of cardiomyocyte maturation and proliferation in neonatal mice. To test the role of Igf1r as a pivotal factor in cardiac regeneration, we knocked down (KD) Igf1r specifically in cardiomyocytes using recombinant adeno-associated virus (rAAV) delivery and troponin T promotor driven shRNAmirs. Cardiomyocyte specific Igf1r KD versus control mice were subjected to experimental MI by permanent ligation of the left anterior descending artery (LAD). Cardiac functional and morphological data were analyzed over a 21-day period. Neonatal Igf1r KD mice showed reduced systolic cardiac function and increased fibrotic cardiac remodeling 21 days post injury. This cardiac phenotype was associated with reduced cardiomyocyte nuclei mitosis and decreased AKT and ERK phosphorylation in Igf1r KD, compared to control neonatal mouse hearts. Our in vivo murine data show that Igf1r KD shifts neonatal cardiac regeneration to a more adult-like scarring phenotype, identifying cardiomyocyte-specific Igf1r signaling as a crucial component of neonatal cardiac regeneration., (© 2024. The Author(s).)

The lignan secoisolariciresinol (SECO) diglucoside (SDG) is a phytoestrogen with diverse effects. LuUGT74S1 glucosylates SECO to SDG, whereby only small amounts of the monoglucoside SMG are formed intermediately, which exhibit increased activity. To identify critical amino acids that are important for enzymatic activity and the SMG/SDG ratio, 3D structural modeling and docking, as well as site-directed mutation studies, were performed. Enzyme assays with ten mutants revealed that four of them had identical kinetic data to LuUGT74S1, while three showed reduced and one increased catalytic efficiency k cat / K m . S82F and E189L substitutions resulted in the complete absence of activity. A17 and Q136 are crucial for the conversion of SMG to SDG as A17S and Q136F mutants exhibited the highest SMG/SDG ratios of 0.7 and 0.4. Kinetic analyses show that diglucosylation is an essentially irreversible reaction, while monoglycosylation is kinetically favored. The results lay the foundation for the biotechnological production of SMG.

Objectives: Rheumatoid arthritis (RA) is associated with an increased risk for osteoporosis and osteoporotic fractures. Since the treatment of RA has improved significantly in recent years, we can expect RA-associated osteoporosis to decrease with good disease control. Therefore, we conducted a retrospective study to investigate whether the frequency of osteoporosis and osteoporotic fractures has changed during 24 years in RA., Methods: We analysed the data of 1.086 RA patients from the time of the first osteological assessment with bone mineral density (BMD) measurement and collection of osteologically important data during the years 1996 and 2019 at our clinic. According to the treatment period, the patients were divided into cohort 1 (investigation between 1996 and 2004; n=539) and cohort 2 (investigation between 2005 and 2019; n=547). The data of the two cohorts were compared, and predictors of BMD were analysed by linear regression analysis., Results: Prevalence of osteoporosis (28.3% vs 48.4%; p<0.001) as well as osteoporotic peripheral fractures (11.5% vs 21%; p<0.001) and vertebral fractures (6.6% vs 10.9%; p=0.011) were significantly lower and treatment with biologicals (19.7% vs 5.0%; p<0.001) significantly more common and glucocorticoid use was significantly less common (p=0.005) in cohort 2. In RA patients with a disease duration of more than 2 years, BMD was significantly higher under treatment with biologicals (p<0.001) despite increased cumulative glucocorticoid dosages (p<0.001)., Conclusion: Our study showed a significant decline in osteoporosis and osteoporotic fractures in RA for 24 years. This positive effect is associated with the more frequent use of biologicals in the years between 2005 and 2019., 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.)

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form (www.icmje.org/disclosure-of-interest/) and declare: no support from any organisation for the submitted work. DM declares he is a member of The BMJ’s regional advisory board for North America. GSC is a National Institute for Health and Care Research (NIHR) senior investigator, the director of the UK EQUATOR Centre, editor-in-chief of BMC Diagnostic and Prognostic Research, and a statistics editor for The BMJ. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care.

Passive smartphone measures hold significant potential and are increasingly employed in psychological and biomedical research to capture an individual's behavior. These measures involve the near-continuous and unobtrusive collection of data from smartphones without requiring active input from participants. For example, GPS sensors are used to determine the (social) context of a person, and accelerometers to measure movement. However, utilizing passive smartphone measures presents methodological challenges during data collection and analysis. Researchers must make multiple decisions when working with such measures, which can result in different conclusions. Unfortunately, the transparency of these decision-making processes is often lacking. The implementation of open science practices is only beginning to emerge in digital phenotyping studies and varies widely across studies. Well-intentioned researchers may fail to report on some decisions due to the variety of choices that must be made. To address this issue and enhance reproducibility in digital phenotyping studies, we propose the adoption of preregistration as a way forward. Although there have been some attempts to preregister digital phenotyping studies, a template for registering such studies is currently missing. This could be problematic due to the high level of complexity that requires a well-structured template. Therefore, our objective was to develop a preregistration template that is easy to use and understandable for researchers. Additionally, we explain this template and provide resources to assist researchers in making informed decisions regarding data collection, cleaning, and analysis. Overall, we aim to make researchers' choices explicit, enhance transparency, and elevate the standards for studies utilizing passive smartphone measures., (© 2024. The Author(s).)

A 69-year-old male patient with seropositive erosive rheumatoid arthritis (RA) presented to our clinic due to progressive dyspnea. High-resolution computed tomography (HRCT) and immunological bronchioalveolar lavage revealed ground-glass opacities and a lymphocytic alveolitis caused by interstitial lung disease (ILD) in RA. Considering previous forms of treatment, disease-modifying antirheumatic drug (DMARD) treatment was switched to tofacitinib. Tofacitinib treatment demonstrated a 33% reduction in ground-glass opacities by artificial intelligence-based quantification of pulmonary HRCT over the course of 6 months, which was associated with an improvement in dyspnea symptoms. In conclusion, tofacitinib represents an effective anti-inflammatory therapeutic option in the treatment of RA-ILD., (© 2023. The Author(s).)

Objectives: Inflammatory rheumatic diseases (IRD) are often associated with interstitial lung disease (ILD). The aim of the present study was to establish a correlation between the findings on HRCT and the immunological bronchoalveolar lavage (BAL)., Methods: The study included 74 patients with newly diagnosed IRD and evidence of ILD on HRCT with the following pattern: ground-glass opacities (GGO), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Patients with other HRCT pattern were excluded. No patient received any immunosuppressive therapy. In addition to HRCT, immunological BAL was performed and the American Thoracic Society clinical practice guideline were used to define BAL patterns (lymphocytic cellular pattern, neutrophilic cellular pattern, eosinophilic cellular pattern and unspecified pattern)., Results: The main HRCT patterns were NSIP (47.3%), GGO (33.8%), and UIP (18.9%). BAL patterns showed the following distribution: 41.9% lymphocytic cellular pattern, 23.0% neutrophilic cellular pattern, 18.9% eosinophilic cellular pattern, and 16.2% unspecific cellular pattern. Placing these data in the context of the HRCT findings, the lymphocytic cellular BAL pattern (48%) was most commonly BAL pattern associated with GGO pattern in HRCT, whereas neutrophilic and lymphocytic cellular BAL patterns were the dominant feature in NSIP and UIP., Conclusion: In patients with new-onset IRD and ILD, inflammatory pulmonary changes are predominate, reflected by GGO on HRCT and a mainly lymphocytic cell profile in the immunological BAL. In NSIP or UIP on HRCT, the percentages of lymphocytes and neutrophils were higher in BAL fluid, representing a fibrotic component in addition to the inflammation. Consequently, patients with evidence of GGO on HRCT should primarily be treated with anti-inflammatory/immunosuppressive therapy, whereas in patients with NSIP and UIP a combination of anti-inflammatory and anti-fibrotic agents would be the appropriate treatment., (© 2024. The Author(s).)

The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity ( n = 28/35) for HPV16 and HPV33 and a specificity of 97% ( n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% ( n = 17/20), while in samples with <750 µL plasma, it was 73% ( n = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC., Competing Interests: T.W. serves on advisory boards for Merck, Sharp & Dohme (MSD). S.L. serves on advisory Boards of MSD, Bristol Myers, Squibb (BMS), and Astra Zeneca (AZ) and has received honoraria from MSD, BMS, AZ, and Merck Serono. D.L.F. has received research funding or in-kind funding from BMS, Calico, Predicine, BostonGene, and NeoGenomics and has received consulting fees from Merck, Noetic, Chrysalis Biomedical Advisors, Arcadia, and Focus. He receives salary support from National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) K23 DE029811, NIH/NIDCR R03DE030550, and NIH/National Cancer Institute R21CA267152.

Objective: The possibility of combining real and virtual environments is driving the increased use of augmented reality (AR) in education, including medical training. The aim of this multicentre study was to evaluate the students' perspective on the AR-based Rheumality GO!® app as a new teaching concept, presenting six real anonymized patient cases with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA)., Methods: The study encompassed 347 undergraduate medical students (232 women and 115 men) from four medical universities in Germany (Jena, Bad Nauheim/Gießen, Nuremberg, Erlangen). The course was divided into a theoretical refresher lecture followed by six AR-based cases in each of the three indications presented in the Rheumality GO! app. All participants evaluated the course after completion, assessing the benefit of the app from a student's perspective using a questionnaire with 16 questions covering six subject areas., Results: The use of the AR-based app Rheumality GO! improved the understanding of pathologies in RA, PsA and axSpA for 99% of the participants. For 98% of respondents, the concept of AR with real patient data has made a positive impact on the teaching environment. On the other hand, 82% were in favour of the use of virtual tools (e.g. AR) in addition to this conventional approach., Conclusion: The results of our survey showed that from the medical students' perspective, an AR-based concept like the Rheumality GO! app can complement rheumatology teaching in medical school as an effective and attractive tool though not replace bedside teaching., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In bacteria, the availability of environmental inorganic phosphate is typically sensed by the conserved PhoR-PhoB two-component signal transduction pathway, which uses the flux through the PstSCAB phosphate transporter as a readout of the extracellular phosphate level to control phosphate-responsive genes. While the sensing of environmental phosphate is well-investigated, the regulatory effects of cytoplasmic phosphate are unclear. Here, we disentangle the physiological and transcriptional responses of Caulobacter crescentus to changes in the environmental and cytoplasmic phosphate levels by uncoupling phosphate uptake from the activity of the PstSCAB system, using an additional, heterologously produced phosphate transporter. This approach reveals a two-pronged response of C. crescentus to phosphate limitation, in which PhoR-PhoB signaling mostly facilitates the utilization of alternative phosphate sources, whereas the cytoplasmic phosphate level controls the morphological and physiological adaptation of cells to growth under global phosphate limitation. These findings open the door to a comprehensive understanding of phosphate signaling in bacteria., (© 2024. The Author(s).)

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members towards one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but non-financial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analysing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated towards COVID-19 elimination (zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases towards advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Volatility of organic aerosols (OAs) significantly influences new particle formation and the occurrence of particulate air pollution. However, the relationship between the volatility of OA and the level of particulate air pollution (i.e., particulate matter concentration) is not well understood. In this study, we compared the chemical composition (identified by an ultrahigh-resolution Orbitrap mass spectrometer) and volatility (estimated based on a predeveloped parametrization method) of OAs in urban PM 2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) samples from seven German and Chinese cities, where the PM 2.5 concentration ranged from a light (14 μg m -3 ) to heavy (319 μg m -3 ) pollution level. A large fraction (71-98%) of compounds in PM 2.5 samples were attributable to intermediate-volatility organic compounds (IVOCs) and semivolatile organic compounds (SVOCs). The fraction of low-volatility organic compounds (LVOCs) and extremely low-volatility organic compounds (ELVOCs) decreased from clean (28%) to heavily polluted urban regions (2%), while that of IVOCs increased from 34 to 62%. We found that the average peak area-weighted volatility of organic compounds in different cities showed a logarithmic correlation with the average PM 2.5 concentration, indicating that the volatility of urban OAs increases with the increase of air pollution level. Our results provide new insights into the relationship between OA volatility and PM pollution levels and deepen the understanding of urban air pollutant evolution.

An 83-year-old male patient presented due to a 3-week history of swelling of the tongue with tongue pain on eating, yellowish plaques, and a gray-brown lesion in the anterior portion of the tongue. Sudden loss of vision in the left eye and temporal headache occurred 3 days before presentation. Due to elevated C‑reactive protein, sonography of the supraaortic arteries as well as positron emission tomography/computed tomography was performed. Imaging revealed inflammation of the great arteries as well as a halo sign on ultrasound of the temporal artery. Thus, a diagnosis of giant cell arteritis with necrosis of the tongue was made. Immunosuppressive therapy with glucocorticoids was initiated. Necrosis of the tongue is a rare manifestation of giant cell arteritis that requires immediate immunosuppressive therapy to prevent further complications to the tongue (e.g., complete necrosis of the tongue, superinfection, tongue amputation)., (© 2023. The Author(s).)

Objectives: In recent years, dental implants are increasing in popularity due to their high success rate, demonstrated functionality, and aesthetic treatment results. Scientific research is very active in proposing improvements in the quality and survival of implants, taking into consideration various aspects. The objective of this study was to provide a holistic epidemiologic view of the state of dental implants, using a systematic approach based on a multimethod SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis and AHP (analytical hierarchical process) qualitative-quantitative analysis to identify the characteristics that can determine their success or failure., Materials and Methods: The study used the hybrid method of SWOT-AHP., Results: Analysis of the results showed that among strengths, the skill of the dentist was considered the most important factor, followed by the success of dental implants in the old people; among weaknesses, bruxism and chronic diseases were highlighted; for opportunities, biomechanical behavior, in terms of good mechanical strength and good tribological resistance to chemical and physical agents in the oral cavity, were considered the most important factors; finally, among threats, medical liability and biomechanical problems had equal weight., Conclusions: This study applied a multimethod SWOT-AHP approach to bring out favorable or critical evidence on the topic of dental implants. In accordance with the result of the strategic vector identified in the Twisting zone Adjustment type section, showed that implant surgery is a widespread technique but always needs improvement to increase the likelihood of success and reduce the complications that can lead to implant failure., (© 2024 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

1,4-Bis(iodomethyl)benzene and 1,3,5-tris(iodomethyl)benzene were used as initiators for the cationic ring-opening polymerization (CROP) of 2-ethyl-2-oxazoline (EtOx) and its copolymerization with tert -butyl (3-(4,5-dihydrooxazol-2-yl)propyl)carbamate (BocOx) or methyl 3-(4,5-dihydrooxazol-2-yl)propanoate (MestOx). Kinetic studies confirmed the applicability of these initiators. Termination with suitable nucleophiles resulted in two- and three-armed cross-linkers featuring acrylate, methacrylate, piperazine-acrylamide, and piperazine-methacrylamide as polymerizable ω-end groups. Matrix-assisted laser desorption/ionization mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy confirmed the successful attachment of the respective ω-end groups at all initiation sites for every prepared cross-linkers. Except for acrylate, each ω-end group remained stable during deprotection of BocOx containing cross-linkers. The cryogels were prepared using EtOx-based cross-linkers, as confirmed by solid-state NMR spectroscopy, scanning electron microscopy, and thermogravimetric analysis. Stability tests revealed a complete dissolution of the acrylate-containing gels at pH = 14, whereas the piperazine-acrylamide-based cryogels featured excellent hydrolytic stability., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: Clinical study reports (CSRs) are highly detailed documents that play a pivotal role in medicine approval processes. Though not historically publicly available, in recent years, major entities including the European Medicines Agency (EMA), Health Canada, and the US Food and Drug Administration (FDA) have highlighted the importance of CSR accessibility. The primary objective herein was to determine the proportion of CSRs that support medicine approvals available for public download as well as the proportion eligible for independent researcher request via the study sponsor., Study Design and Setting: This cross-sectional study examined the accessibility of CSRs from industry-sponsored clinical trials whose results were reported in the FDA-authorized drug labels of the top 30 highest-revenue medicines of 2021. We determined (1) whether the CSRs were available for download from a public repository, and (2) whether the CSRs were eligible for request by independent researchers based on trial sponsors' data sharing policies., Results: There were 316 industry-sponsored clinical trials with results presented in the FDA-authorized drug labels of the 30 sampled medicines. Of these trials, CSRs were available for public download from 70 (22%), with 37 available at EMA and 40 at Health Canada repositories. While pharmaceutical company platforms offered no direct downloads of CSRs, sponsors confirmed that CSRs from 183 (58%) of the 316 clinical trials were eligible for independent researcher request via the submission of a research proposal. Overall, 218 (69%) of the sampled clinical trials had CSRs available for public download and/or were eligible for request from the trial sponsor., Conclusion: CSRs were available from 69% of the clinical trials supporting regulatory approval of the 30 medicines sampled. However, only 22% of the CSRs were directly downloadable from regulatory agencies, the remaining required a formal application process to request access to the CSR from the study sponsor., Competing Interests: Declaration of competing interest A/Prof Rowland and Prof Sorich are recipients of investigator-initiated funding for research outside the scope of the current study from AstraZeneca, Boehringer Ingelheim, Pfizer, and Takeda. A/Prof Rowland is a recipient of speaker fees from Boehringer Ingelheim and Genentech. Professor Swain reports grant to institution from Genentech-Roche and paid non-promotional speaking, consulting, and in-kind manuscript writing from Genentech–Roche. Professor Swain also reports grants to institution from Kailos Genetics. Professor Swain reports consulting fees paid from Athenex, Sanofi, AstraZeneca, Daiichi Sankyo, Lilly Pharmaceuticals, Merck, Molecular Templates, Biotheranostics, Natera, and Exact Sciences. Professor Swain reports support for attending meetings and travel from Sanofi, Daichi Sankyo, and Roche/Genentech. Third party in-kind manuscript writing from AstraZeneca. Dr Ross currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), and from Arnold Ventures; formerly received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology (NEST) and from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644); and in addition, Dr Ross was an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. that was settled September 2022. Frank Rockhold receives research support from NIH, PCORI, BMS, AZ, American Regent, Gates Foundation, Eidos; Consulting for Janssen, Clover, Doctor Evidence and Intercept; DSMB for Lilly, AZ, Merck, Gilead, Novartis, Icosavax, Sanofi, UCB, Amgen, Biogen, BMS, pulmocide, Alkermes, Diurnal; nonprofit chairman of the board (unpaid) for Frontier Science Foundation; stock/stock options from GSK, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, Adaptic Health. Dr Areti Angeliki Veroniki is a Statistical Associate Editor for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. The author team has no other potential conflicts of interest with respect to this research and/or publication to declare., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction : The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods : A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results : A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus , Streptococcus species, Enterococcus faecalis , Kingella kingae , Neisseria gonorrhoeae , and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion : The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting., Competing Interests: At least one of the (co-)authors is a member of the editorial board of Journal of Bone and Joint Infection. The peer-review process was guided by an independent editor, and the authors also have no other competing interests to declare., (Copyright: © 2024 Stéphanie Pascual et al.)

Objective: To assess and compare the diagnostic performance of Clinical Prediction Rules (CPRs) developed to detect group A Beta-haemolytic streptococci in people with acute pharyngitis (or sore throat)., Study Design: A systematic review., Methods: We searched PubMed, Embase and Web of Science (inception-September 2022) for studies deriving and/or validating CPRs comprised of ≥2 predictors from an individual's history or physical examination. Two authors independently screened articles, extracted data and assessed risk of bias in included studies. A meta-analysis was not possible due to heterogeneity. Instead we compared the performance of CPRs when they were validated in the same study population (head-to-head comparisons). We used a modified grading of recommendations, assessment, development, and evaluations (GRADE) approach to assess certainty of the evidence., Results: We included 63 studies, all judged at high risk of bias. Of 24 derived CPRs, 7 were externally validated (in 46 external validations). Five validation studies provided data for head-to-head comparison of four pairs of CPRs. Very low certainty evidence favoured the Centor CPR over the McIsaac (2 studies) and FeverPain CPRs (1 study) and found the Centor CPR was equivalent to the Walsh CPR (1 study). The AbuReesh and Steinhoff 2005 CPRs had a similar poor discriminative ability (1 study). Within and between study comparisons suggested the performance of the Centor CPR may be better in adults (>18 years)., Conclusion: Very low certainty evidence suggests a better performance of the Centor CPR. When deciding about antibiotic prescribing for pharyngitis patients, involving patients in a shared decision making discussion about the likely benefits and harms, including antibiotic resistance, is recommended. Further research of higher rigour, which compares CPRs across multiple settings, is needed., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Of over 8,000 recorded randomised trials addressing COVID-19, around 80% were of treatments, and 17% have reported results. Approximately 1% were adaptive or platform trials, with 25 having results available, across 29 journal articles and 10 preprint articles., Methods: We conducted an extensive literature review to address four questions about COVID-19 trials, particularly the role and impact of platform/adaptive trials and lessons learned., Results: The key findings were: Q1. Social value in conducting trials and uptake into policy ? COVID-19 drug treatments varied substantially and changed considerably, with drugs found effective in definitive clinical trials replacing unproven drugs. Dexamethasone has likely saved ½-2 million lives, and was cost effective across a range of countries and populations, whereas the cost effectiveness of remdesivir is uncertain. Published economic and health system impacts of COVID-19 treatments were infrequent. Q2. Issues with adaptive trial design s. Of the 77 platform trials registered, 6 major platform trials, with approximately 50 treatment arms, recruited ~135,000 participants with funding over $100 million. Q3. Models of good practice. Streamlined set-up processes such as flexible and fast-track funding, ethics, and governance approvals are vital. To facilitate recruitment, simple and streamlined research processes, and pre-existing research networks to coordinate trial planning, design, conduct and practice change are crucial to success. Q4. Potential conflicts to avoid? When treating patients through trials, balancing individual and collective rights and allocating scarce resources between healthcare and research are challenging. Tensions occur between commercial and non-commercial sectors, and academic and public health interests, such as publication and funding driven indicators and the public good., Conclusion: There is a need to (i) reduce small, repetitive, single centre trials, (ii) increase coordination to ensure robust research conducted for treatments, and (iii) a wider adoption of adaptive/platform trial designs to respond to fast-evolving evidence landscape., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Glasziou P et al.)

Goal: Auto-injectors for self-administration of drugs are usually refrigerated. If not warmed up prior to the injection, ejection of the total drug volume is not guaranteed, as their spring and plunger mechanism cannot adjust for a change in viscosity of the drug. Here, we develop piezoelectric micro diaphragm pump that allows these modifications possible while investigating the effectiveness of this alternative dosing method. Methods: The dosing of highly viscous liquid of 25 mPa·s is made possible using application-specific micropump design. By comparing the analytical with experimental results, the practicality of the concept is verified. Results: Using a powerful piezoelectric stack actuator, the micropump achieves high fluid pressures of up to (368 ± 17) kPa. In order to assess the influence of viscosity, we characterize the fluidic performance of the designed micropump through 27G gauge needle for various water-glycerin mixtures. We find maximum flow rates of 2 mL/min for viscosities of up to 25 mPa·s. Conclusions: The developed micro diaphragm pump enables the development of smart auto-injectors with flow rate regulation to achieve drug delivery for high viscosity drugs through 27G needles., (© 2024 The Authors.)

Background: The field of eHealth is growing rapidly and chaotically. Health care professionals need guidance on reviewing and assessing health-related smartphone apps to propose appropriate ones to their patients. However, to date, no framework or evaluation tool fulfills this purpose., Objective: Before developing a tool to help health care professionals assess and recommend apps to their patients, we aimed to create an overview of published criteria to describe and evaluate health apps., Methods: We conducted a systematic review to identify existing criteria for eHealth smartphone app evaluation. Relevant databases and trial registers were queried for articles. Articles were included that (1) described tools, guidelines, dimensions, or criteria to evaluate apps, (2) were available in full text, and (3) were written in English, French, German, Italian, Portuguese, or Spanish. We proposed a conceptual framework for app evaluation based on the dimensions reported in the selected articles. This was revised iteratively in discussion rounds with international stakeholders. The conceptual framework was used to synthesize the reported evaluation criteria. The list of criteria was discussed and refined by the research team., Results: Screening of 1258 articles yielded 128 (10.17%) that met the inclusion criteria. Of these 128 articles, 30 (23.4%) reported the use of self-developed criteria and described their development processes incompletely. Although 43 evaluation instruments were used only once, 6 were used in multiple studies. Most articles (83/128, 64.8%) did not report following theoretical guidelines; those that did noted 37 theoretical frameworks. On the basis of the selected articles, we proposed a conceptual framework to explore 6 app evaluation dimensions: context, stakeholder involvement, features and requirements, development processes, implementation, and evaluation. After standardizing the definitions, we identified 205 distinct criteria. Through consensus, the research team relabeled 12 of these and added 11 more-mainly related to ethical, legal, and social aspects-resulting in 216 evaluation criteria. No criteria had to be moved between dimensions., Conclusions: This study provides a comprehensive overview of criteria currently used in clinical practice to describe and evaluate apps. This is necessary as no reviewed criteria sets were inclusive, and none included consistent definitions and terminology. Although the resulting overview is impractical for use in clinical practice in its current form, it confirms the need to craft it into a purpose-built, theory-driven tool. Therefore, in a subsequent step, based on our current criteria set, we plan to construct an app evaluation tool with 2 parts: a short section (including 1-3 questions/dimension) to quickly disqualify clearly unsuitable apps and a longer one to investigate more likely candidates in closer detail. We will use a Delphi consensus-building process and develop a user manual to prepare for this undertaking., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42021227064; https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021227064., (©Janette Ribaut, Annette DeVito Dabbs, Fabienne Dobbels, Alexandra Teynor, Elisabeth Veronica Mess, Theresa Hoffmann, Sabina De Geest. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 15.01.2024.)

Background: Many guidelines recommend non-drug interventions (NDIs) for managing common conditions in primary care. However, compared with drug interventions, NDIs are less widely known, promoted and used. We aim to (1) examine general practitioners' (GPs') knowledge, attitudes and practices for NDIs, including their use of the Royal Australian College of General Practitioners (RACGP) Handbook of Non-Drug Interventions (HANDI), and (2) identify factors influencing their use of NDIs and HANDI., Methods: We conducted a web-based cross-sectional survey of practicing GP members in Australia during October-November 2022. The survey contained five sections: characteristics of GP; knowledge and use of NDIs; attitudes towards NDIs; barriers and enablers to using HANDI; and suggestions of NDIs and ideas to improve the uptake of NDIs in primary care., Results: Of the 366 GPs who completed the survey, 242 (66%) were female, and 248 (74%) were ≥45 years old. One in three GPs reported that they regularly ('always') recommend NDIs to their patients when appropriate (34%), whereas one-third of GPs were unaware of HANDI (39%). GPs identified several factors that improve the uptake of HANDI, including 'access and integration of HANDI in clinical practice', 'content and support to use in practice' and 'awareness and training'., Conclusions: While many GPs are aware of the effectiveness of NDIs and often endorse their use, obstacles still prevent widespread adoption in primary care. The results of this survey can serve as a foundation for developing implementation strategies to improve the uptake of effective evidence-based NDIs in primary care., 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.)

Network models are increasingly used to study infectious disease spread. Exponential Random Graph models have a history in this area, with scalable inference methods now available. An alternative approach uses mechanistic network models. Mechanistic network models directly capture individual behaviors, making them suitable for studying sexually transmitted diseases. Combining mechanistic models with Approximate Bayesian Computation allows flexible modeling using domain-specific interaction rules among agents, avoiding network model oversimplifications. These models are ideal for longitudinal settings as they explicitly incorporate network evolution over time. We implemented a discrete-time version of a previously published continuous-time model of evolving contact networks for men who have sex with men and proposed an ABC-based approximate inference scheme for it. As expected, we found that a two-wave longitudinal study design improves the accuracy of inference compared to a cross-sectional design. However, the gains in precision in collecting data twice, up to 18%, depend on the spacing of the two waves and are sensitive to the choice of summary statistics. In addition to methodological developments, our results inform the design of future longitudinal network studies in sexually transmitted diseases, specifically in terms of what data to collect from participants and when to do so., Competing Interests: Competing interestsThe authors have no Conflict of interest to report., (© The Author(s) 2024.)

At the beginning of 2023, there have been significant changes to the regulations for outpatient surgery in Germany, which were set out in a trilateral self-administration agreement between the umbrella association of statutory health insurance companies, the German Hospital Association and the Federal Association of Statutory Health Insurance Physicians. Among other things, a catalog stated circumstances under which an operation should not be carried out on an outpatient basis or should only be carried out with doubt. This catalog explains the patient's age: up to the first year of life, inpatient performance of a service can be justified. This formulation in itself means that children from one year of age on should regularly undergo outpatient surgery.In the german scientific societies for otolaryngology, head and neck surgery as well as for anesthesiology and intensive care medicine, doubts arose as to whether this age limit could also be scientifically justified for operations in the throat such as adenotomy or tonsillotomy.A search was carried out in international guidelines and in the international literature and the statements were evaluated. The results of this literature search were discussed with representatives of the Pediatric Otorhinolaryngology Working Group (AG PädHNO) of the German Society for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) and the scientific working group for pediatric anesthesia (WAKKA) of the German Society for Anesthesiology and Intensive Care Medicine (DGAI) in conferences.The consensus revealed that a strict age limit of the first year of life is not appropriate for the outpatient performance of adenotomies and tonsillotomies. First of all, specifying a strict age limit is questionable because, regardless of age, a number of other medical and social factors influence the responsible performance of outpatient operations. Furthermore, the age limit of one year is not considered appropriate in view of literature, guidelines and practical experience in the international area. The assessment of the literature and the consideration of the implementation in the international area make an age limit in the range of 2-3 years seem more appropriate.This review provides the responsible doctors with a variety of insights, aspects and arguments so that they can make their decision to carry out these operations on an outpatient or inpatient basis appropriately and responsibly., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)